摘要:

ISSN 0265-0568 NPRRDF 13(2) 75-1 76 (1 996) Natural Product Reports A journal of current developments in bioorganic chemistry Volume 13 Number 2 CONTENTS ... 111 Hot off the Press Robert A. Hill and Andrew R. Pitt Reviewing the recent literature on natural products and bioorganic chemistry 75 Marine Natural Products D. John Faulkner Reviewing the literature published in 1994 127 P-Phenylethylamines and the Isoquinoline Alkaloids K. W. Bentley Reviewing the literature published between July 1994 and June 1995 151 Tri terpenoids Joseph D. Connolly and Robert A. Hill Reviewing the literature published in 1994 171 Amaryllidaceae and Sceletium Alkaloids John R. Lewis Reviewing the literature published in 1994 Cumulative Contents of Volume 13 Number 1 1 Modern Bioassays using Metal Chelates as Luminescent Probes Peter G.Sammes and Gokhan Yahioglu 29 The DAP Pathway to Lysine as a Target for Antimicrobial Agents (up to September 1995) Russell J. Cox 45 The Biosynthesis of Plant Alkaloids and Nitrogenous Microbial Metabolites (1994) Richard B. Herbert 59 Diterpenoids (1994) James R. Hanson 73 Book Reviews Anticancer Drugs from Animals Plants and Microorganisms by George R. Pettit Fiona H. Pierson and Cherry L. Herald (reviewed by John Mann); Oxidative Stress and Antioxidant Defenses in Biology ed. S. Ahmad (reviewed by David J. Robins); Advances in Nitrogen Heterocycles (Volume I) ed C. J. Moody (reviewed by Joseph P. Michael) Number 2 75 Marine Natural Products (1994) D.John Faulkner 127 ,8-Phenylethylamines and the Isoquinoline Alkaloids (July 1994 to June 1995) K. W. Bentley 15 I Triterpenoids (1994) Joseph D. Connolly and Robert A. Hill 171 Amaryllidaceae and Sceletium Alkaloids (1994) John R. Lewis Articles that will appear in forthcoming issues include The Biosynthesis and Degradation of Thiamin (Vitamin B,) (January 1986 to January 1996) Tadhg P. Begley Pyrrolizidine Alkaloids (July 1994 to June 1995) J. Richard Liddell Monoterpenoids (1991 1992 andpart of 1993) David H. Grayson Steroids Reactions and Partial Synthesis (1994) James R. Hanson Recent Progress in the Chemistry of Non-monoterpenoid Indole Alkaloids (July 1994 to June 1995) Masataka Ihara and Keiichiro Fukumoto Dietary Antioxidants in Disease Prevention Michael H. Gordon Natural Sesquiterpenoids (1994) Braulio M. Fraga

ISSN:0265-0568    

DOI:10.1039/NP99613FP003

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Natural Product Reports Editorial Board Professor T. J. Simpson (Chairman) Dr J. R. Hanson Dr R. B. Herbert Professor J. Mann Professor D. J. Robins Dr C. J. Schofield Dr D. A. Whiting Editorial Staff Dr Sheila R. Buxton Managing Editor Dr Roxane M. Owen Deputy Editor Miss Nicola P. Coward Production Editor Dr Anthony P. Breen Mr Michael J. Francis Technical Editors Miss Daphne E. Houston Miss Karen L. White Edito ria I Secretaries ~ University of Bristol University of Sussex University of Leeds University of Reading University of Glasgow University of Oxford University of Nottingham Editorial Office The Royal Society of Chemistry Thomas Graham House Science Park Milton Road Cambridge UK CB4 4WF Telephone +44 (0)1223 420066 Facsimile +44 (0)1223 420247 E-mail rscl @rsc.org RSC Server http://c h em ist ry.rsc.0 rg/rsc/ Natural Product Reports is a bimonthly journal of critical reviews.It aims to foster progress in the study of bioorganic chemistry by providing regular and comprehensive reviews of the relevant literature published during well-defined periods. Topics include the isolation structure biosynthesis biological activity and chemistry of the major groups of natural products -alkaloids terpenoids and steroids aliphatic aromatic and 0-heterocyclic compounds. This is augmented by frequent reviews of the wider context of bioorganic chemistry including developments in enzymology nucleic acids genetics chemical ecology primary and secondary metabolism and isolation and analytical techniques which will be of general interest to all workers in the area.Articles in Natural Product Reports are commissioned by members of the Editorial Board or accepted by the Chairman for consideration at meetings of the Board. Natural Product Reports (ISSN 0265-0568) is published bimonthly by The Royal Society of Chemistry Thomas Graham House Science Park Milton Road Cambridge UK CB4 4WF. 1996 Annual Subscription Price EEA f325.00 USA $615.00 Rest of World €333.00. Change of address and orders with payment in advance to The Royal Society of Chemistry The Distribution Centre Blackhorse Road Letchworth Herts. UK SG6 IHN. Air Freight and mailing in the USA by Publications Expediting Service Inc.200 Meacham Avenue Elmont NY 11003. US Postmaster send address changes to Natural Product Reports Publications Expediting Service Inc. 200 Meacham Avenue Elmont NY 11003. Second-Class postage paid at Jamaica NY 11431-9998. All other despatches outside the UK are by Bulk Airmail within Europe and Accelerated Surface Post outside Europe. Printed in the UK. Members of the Royal Society of Chemistry should order the journal from The Membership Manager The Royal Society of Chemistry Thomas Graham House Science Park Milton Road Cambridge UK CB4 4WF. 0 The Royal Society of Chemistry 1996 All Rights Reserved No part of this publication may be reproduced stored in a retrieval system or transmitted in any form or by any means electronic mechanical photographic recording or otherwise without the prior permission of the publishers. Printed in Great Britain by the University Press Cambridge Subscription rates for 1996 EEA f325.00 USA $615.00 Rest of World f333.00

ISSN:0265-0568    

DOI:10.1039/NP99613FX005

出版商:RSC    

年代:1996

数据来源: RSC

ISSN:0265-0568    

DOI:10.1039/NP99613BX007

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Marine Natural Products D. John Faulkner Scripps Institution of Oceanography University of California San Diego La Jolla CA 92093-02 12 USA ~~~~~~~~ ~~ Reviewing the literature published during 1994 (Continuing the coverage of literature in Natural Product Reports 1995 Vol. 12 p. 223) 1 Introduction 2 Marine Microorganisms and Phytoplankton 3 Green Algae 4 Brown Algae 5 Red Algae 6 Sponges 7 Coelenterates 8 Bryozoans 9 Molluscs 10 Tunica tes 11 Echinoderms 12 Miscellaneous 13 References 1 Introduction This Report is a review of the literature of marine natural product chemistry for 1994. Earlier reports published in this journal cover the period from 1977 to December 1993.'-" The format for this review is identical to that of the previous reports except that compounds from cyanobacteria (or blue-green algae) are now included in the section on marine microorganisms and phytoplankton.The review does not provide a comprehensive coverage of all research involving chemicals from marine organisms but concentrates on reports of novel marine natural products with interesting biological and pharmaceutical properties. Biochemical studies involving marine organisms and reports of primary metabolites are specifically omitted. Research on the biosynthesis of marine natural products has been reviewed in detail elsewherel2 l3and is not included in this report. Wherever possible the biological and pharmacological properties of new marine natural products have been reported but papers detailing the pharmacological studies are beyond the scope of this review.In the area of synthetic organic chemistry the review focuses on reports of the total synthesis of marine natural products or close analogues particularly those papers that redefine chemical structures. No attempt has been made to review the patent literature or conference abstracts and reports. The spate of excellent reviews that appeared in 1993 was followed by a relative dearth of such reviews in 1994. Four of these reviews 'Oxylipins from marine invertebrates ',14 'Structure and biosynthesis of marine algal oxylipins ',15 'New marine prostanoids clavulones halogenovulones and puna- glandins',16 and 'Aquatic invertebrates open up new pers-pectives in eicosanoid research biosynthesis and bioactivity ',17 all emphasize the wide distribution of eicosanoids and related compounds throughout the marine environment.A short review of 'Strategies for the discovery of secondary metabolites from marine bacteria ' stresses the differences between marine and terrestrial bacteria. An interesting historical account of ciguatera research is found in 'Ciguatera and its off-shoots- chance encounters en route to a molecular structure'.lg A review entitled 'The discovery of marine natural products with therapeutic potential '20 provides a realistic overview of the contributions of marine natural products research to the drug discovery effort. 2 Marine Microorganisms and Phytoplankton Marine bacteria are rapidly becoming recognized as potentially useful sources of compounds of biomedical interest.While it is common to find metabolites previously isolated from terrestrial microorganisms in bacteria from coastal waters those bacteria isolated from deeper waters or from the tissues of marine algae invertebrates and fishes have yielded some interesting new compounds. This is not always the case however as is demonstrated by the isolation of o-aminophenol (1) as the OH Q$yp N 1 H (2) antimicrobial agent from a purple bacterium isolated from a sponge of the genus Adocia.21A symmetrical bis-indole 7,7- bis(3-indolyl)-p-cresol (2) was isolated as an antimicrobial constituent of a Vibrio sp. that was isolated from the marine sponge Hyatella sp.22 Similar bis-indoles vibrindole A (3) and the known metabolite 2,2-di(3-indolyl)-3-indolone (4),23were H H (4) obtained from a strain of Vibrio parahaemolyticus isolated from the toxic mucus of the boxfish Ostracion cubicu~.~~ Trisindoline (5) is an isomer of (4)that was produced by a Vibrio sp.isolated from the sponge Hyrtios ~ltum.~~ Vibriogazogenes ATCC29988 which was isolated from a marine mud sample contained magnesidin A (6)as a mixture of tautomers.26 An isolate of the (5) Mg2+ 2 75 bacterium Pseudomunus fluorescens from the tissues of an unidentified tunicate produced the known metabolite andrimid (7) previously isolated from an Enterobacter SP.,~' and three related compounds moiramides A-C Cultures of a (7) R= a-H (10) R = (3-OH Vibrio sp.(M22-I) which was isolated from a homogenate of the sponge Hyatella sp. also produced andrimid (7).29 Halobacillin (1 l) a member of the iturin class of acylpeptides was produced by a Bacillus species (culture # CND-914) that was isolated from a marine sediment core from the Gulf of Calif~rnia.~~ The stereochemistry of thiomarinol (1 2) which is a metabolite of Alteromonas rava sp. nov. SANK 73390,31 was HO 0 (14) NATURAL PRODUCT REPORTS 1996 determined by chemical and spectroscopic The unusual CSO-carotenoid okadaxanthin (1 3) was isolated from a Pseudornonas sp. (KK10206C) that was isolated from a homogenate of the sponge Halichondria ok~dai.~~ The structures of the bacterial products (1-13) were all elucidated by interpretation of spectroscopic data.A marine actinomycete that was isolated from the surface of the jellyfish Cassiopeia xamachana from the Florida Keys produced two antiinflammatory depsipeptides salinamides A (14) and B (15); the structure of salinamide B (15) was determined by single crystal X-ray diffraction Halichomycin (16) is an unusual tricyclic macrolide that was isolated as the cytotoxic component of Streptornyces hygroscopicus from the digestive tract of the fish Halichoeres bleekeri.35The structural elucidation of this unusual structure is remarkably brief for such a complex molecule. The absolute configurations of octalactins A (17) and B (18) which are metabolites of a Streptornyces sp. isolated from the surface of a gorgonian coral,36 have been determined by two very different total ~yntheses.~'.38 .o / NATURAL PRODUCT REPORTS 1996-D. J. FAULKNER An unidentified fungus perhaps a mixture of two fungi isolated from the sponge Styloidla sp using a sea-water culture medium contained a mixture of nectriapyrones A (19) and B (20) that are similar to a terrestrial fungal metabolite.Jg Chloriolins A-C (21)-(23) are sesquiterpenes of the coriolin Me0 Me0 OH (22) R = OH (23) R= H class that were obtained from a sea-water culture of an unidentified fungus isolated from the sponge Juspis aff. john~toni.~~ The marine fungus Phomu sp. (SANK 11486) isolated from the shell of the crab Chinoecetes opilio produced five macrocyclic diterpenes phomactins B (24) Bl (25) B2 (26) C (27) which was previously known,31 and D (28) which (24) R' = H; R2 = OH (25)R' =OH; R*=H inhibited the binding of platelet aggregation factor (PAF) to its receptors and inhibited PAF-induced platelet aggregati~n.~~ (29) x=4 (32) X= 2 (30) x=3 (33) x= 3 (31) X= 2 (34) x= 4 Br OH The structure of phomactin B (24) was determined by X-ray crystallographic analysis of a derivative and the remaining fungal metabolites were identified by analysis of spectral data.Leptosins A-F (29)-(34) are cytotoxic dimeric diketopiperazine derivatives that were obtained from the fungus Leptosphueriu sp. that was found on the brown alga Surgussum t~rtile.~~ The structures of (29)-(34) were defined by spectroscopic analyses.A report of the chemistry of Lignincolu luevis provides insufficient data to support the unusual structures There are relatively few reports of metabolites from marine cyanobacteria so it is both convenient and appropriate that they be reviewed together with other microorganisms. Curacin A (35) is an antimitotic and antiproliferative agent from a Caribbean collection of Lyngbya rnaju~cula.~~~ 46 After bioassay- guided fractionation using the brine shrimp assay the structure of curacin A (39 which inhibits microtubule assembly and the Br ir (38) binding of colchicine to tubulin was elucidated by spectroscopic methods. A marine strain of Nostoc linckiu produced the potent cytotoxin borophycin (36) the structure of which was de-termined by X-ray ~rystallography.~' The structure of the heterocyst glycolipid from Noduluriu har~eyunu,~~ (3R,25R)-3,25-dihydroxyhexacosyl a-D-glucopyranoside (37) was con- firmed by synthesis.49 The 'sponge ' metabolite 2-(2',4'-dibromophenoxy)-4,6-dibromophenol(38) which is deposited as conspicuous crystals throughout the surface tissues of Dysideu herbucea was found only in cells of the cyanobacterium Oscillutoriu spongeliue and was not associated with sponge or he tero trophic bacteria cells.50 0 HO OH 0 A monogalactosyl diacylglycerol (39) was isolated from cultures of the dinoflagellate Scrippsiella trochoidea and was identified by spectroscopic A new synthesis of symbioramide (40) which is a Ca2+ ATPase activator from a ?H HOT^^^^^- HNFc14H29 0 (W Syrnbiodiniurnsp.isolated from a bivalve,52 has been Three cytotoxins of the amphidinolide B group amphidinolides B (41) B (42) and B (43) were isolated from the free swimming dinoflagellate Amphidinium sp. The structure of amphidinolide B (41) which has identical spectral data to those of amphidinolide B,54was determined by single crystal X-ray diffraction analysis; structures (42) and (43) were elucidated by analysis of spectral data.55 The absolute stereo- chemistry of amphidinolide B or B (41) was determined by chemical degradati~n.~~ The structures of amphidinolides L NATURAL PRODUCT REPORTS 1996 (44),57M (45)5s and N (46)59 and amphidinin A (47),60 all of which were isolated from different strains of the dinoflagellate Amphidinium sp.that were obtained from flatworms of the genus Arnphiscolops were elucidated by interpretation of spectroscopic data. Two okadaic acid esters (48) and (49) were isolated from Prorocentrum lima and their biosynthetic origin was determined by using 13C labelling experiments.61 A structure and partial stereochemistry have been assigned to maitotoxin (50) a metabolite of Garnbierdiscus toxicus which is the most toxic and largest natural non-biopolymer.62 Raikovenal (51) and preraikovenal (52) are two sesquiterpenes from the marine ciliate Euplotes raikovi; raikovenal (51) is toxic at 10-20pgml-' to other ciliates.63 Further studies of the ciliated protist Euplotes crassus have resulted in the isolation of euplotin C (53) and its possible precursor preuplotin (54) which resembles the 1,4-diacetoxydienes that have been obtained previously from green algae of the genus Udote~.~~ Keronopsins A (59 A (56) B (57) and B (58) were reported as chemical defence substances from the ciliate Pseudokeronopsis r~bra.~~ A new domoic acid isomer (59) has been isolated from contaminated Canadian shellfish tissue and from the diatom Nitzschia pungens f.multiseries.66 0 0 (48) R= $&OH (49) R = $&OH NATURAL PRODUCT REPORTS 1996-D. J. FAULKNER yfyy 0 OAc OH (53) H OAc COOH (54) (55) R' = H; R2 = S03Na (59) (56) R' = Br; R2 = S03Na (57) R' = R2 = H (58) R' = Br; R2 = H HO HO OH OAc Br OH Br (60) R-(+)-cinnamyl-1-phenyl-2-propenyl ether (6l) which is a 3 Green Algae metabolite of Cauferpa racemosa,6* was established by an The tropical green alga Avrainviflea rawsonii produces the enantiomeric synthe~is.~~ A study of the chlorophyll-sensitized inosine 5'-monophosphate dehydrogenase inhibitor iso-photodegradation of caulerpenyne (62) which is the major rawsonol (60) the structure of which was elucidated by metabolite of C.taxif~fia,~~ provides a model for the detoxi- interpretation of spectral data.67 The absolute configuration of fication of this group of terpenoids." Three new cycloartenol sulfates (63)-(65) that inhibit protein tyrosine kinase pp60" '"' were isolated from Tydemania expeditionis and were identified by spectroscopic 4 Brown Algae It has been demonstrated that the stereochemistry of giffordene (66) which is a gamete attractant of GifSordia (= Hincksia) mit~hellae,~~ results from the thermolabile hydrocarbon (1,3Z,52,8Z)-undecatetraene via a spontaneous [1,7]-sigmatropic hydrogen shift.74 The absolute configurations of ecklonialactones A (67) B (68) and E (69) from brown algae (67) (68) 6,7-dihydro Q OH \ "H (70) of the genera E~klonia'~ and Egregia,76and neohalicholactone (70) from Laminaria sinclairii originally isolated from the sponge Halichondria ~kadai,'~have been determined from chiroptical data.78-79 The absolute configuration of ( +)-kjellmanianone (7 I) which is an antimicrobial agent from Sargassum kjellmanianum,sO has been revised from R to S as the result of an enantiospecific synthesis natural kjellmanianone is an almost racemic mixture of enantiomers.81- 82 Three halo- genated norsesquiterpenoids 2-chloro-2,6,10-trimethylunde-NATURAL PRODUCT REPORTS 1996 canoic acid (72) 2-bromo-2,6,10-trimethylundecanoic acid (73) and methyl 2-chloro-2-carboxy-6,lO-dimethylundecanoate (74) were isolated from an Indian specimen of Padina tetrastromati~a.~~ One new compound 4-cadinene (75) one new natural product 4-epi-cubebol (76) and four known sesquiterpenoids were isolated from Taonia atom~ria.~~ (72)R = Me; X= CI (73) R=Me; X=Br (74) R=COOMe; X=CI (75) In addition to eight known diterpenes a new metabolite (1R*,2E,4R*,7E,11 R*,12S*)-12,18-dihydroxydolabella-2,7-diene (77) was isolated from a Maltese specimen of Dilophus mediterraneus and was identified by interpretation of spec- troscopic data.85 Six new dolabellanes (78)-(83) and three new (77) HOCr-J -io (79) (80) R = H (81) R =Ac HO& HOQi\Hd oH 7 OAc (82) (83) dolastanes (84)-(86) have been obtained from Dictyota pardalis f.pseudohamata from the Great Barrier Reef. The structures of (1 R,3S,42,62,8R 11R 12R)-12-hydroxydolasta-4,6-dien-9-one 0 (84) R = H (86) (85) R = OAC NATURAL PRODUCT REPORTS 1996D. J. FAULKNER (84) (1R,3E,5S,7E 11R,12R)-5-acet oxy- 12- hydroxydolabella- 3,7-dien-9-one (79) and (1R,3E,7E,9R 1lR,12R)-9-hydroxy-dolabella-3,7-dien- 12-01 (80) were determined by X-ray analyses and the remaining diterpenes were identified by spectroscopic analysis." Dictyota hartayresiana from the Indian Ocean contained one known dolastane five known dolabellanes and five new compounds (lS*,3E,5R*,7E 1IS* 12S*)-5-acetoxy-12- hydroxydolabella-3,7-dien-9-one (87) (lS*,3E 5R*,72 1IS* 12S*)- 5-acetoxy- 12- hydroxydolabella-3,7-dien-9-one (88) which are enantiomers of (79) and (78) respectively (1 R*,3Z,7 E 11 S*) -9 -acetoxydolabella -3,7,12 -trien -16-a1 (89) which is incorrectly drawn in the journal (5R*,8S* 9S* 12S* 14S*)-9-hydroxydolasta- 1,3-dien-6-0ne (90) which appears to be the same as (84) but with a different optical rotation and numbering system and (1 R*,4S*,5R*,SS*,9S* 12S*,14R*)-1,4,9-trihydroxydolasta-2-en-6-0ne (91).88 @ HO" 0 (89) (91) (92) An Argentinean specimen of D.dichotoma contained dictyol D 2P-acetate (92) together with known metabolite^.^^ One new xenicane diterpene 6,7-epoxy-4-hydroxydictyolactone(93) was reported from a Dictyota sp. (= D. ciliolata ?) from Dakar in a paper that discusses thermal isomerizations and con-formational motion in selected xenicane derivative^.^^ (93) The total synthesis of (+)-spat01 (94) which is a metabolite of Spatoglossum ~chmittii,~~ confirmed the absolute configur- ati~n.~~ A similar synthetic route which employs a [2+21 photocycloaddition was the basis of the synthesis of (+)-stoechospermol (95),93 which is a metabolite of Stoechospermum margin~tum.~~ non-photochemical synthesis of racemic A stoechospermol(95) was also reported.g5 (+)-Epoxydictymene (96) which was isolated from Dictyota di~hotoma,~~ has been synthesized using cobalt-mediated chemi~try.~' The diketone (97) from Cystophora moni1iformisg8 has been synthesized in high yield from geranylacet~ne.~~ A new sesquiterpene phenol (98) has been isolated from PerithaZia caudatalOO The absolute stereochemistry at C-17 in the acylphloroglucinol (99) from Distrornium decumbems previously isolated from a Zonaria sp.,lol has been determined by application of Mosher's met hod.lo2 0 0 (97) COOH OH 0 OH I Me0 (99) 5 Red Algae The Caribbean alga Murrayella periclados contains a number of eicosanoids that include (1 2s)- 12-hydroxyeicosatetraenoic acid (loo) (6E)-leukotriene B (101) and erythro and threo 82 NATURAL PRODUCT REPORTS 1996 isomers of hepoxilins B (102)/(103) and B (104)/(105).103 Four new acetogenins (115)-(118) and one new Constanolactones A-G (106)-( 112) are cyclopropyl-containing sesquiterpene (1 19) were isolated together with eleven known oxylipins that were isolated from Constantinea ~irnplex.'*~ metabolites from Laurencia sp.cf. L. gracilis from New A new sphingosine derivative (1 13) was isolated from an Indian Ocean specimen of Halyrnenia d~rivilliae.'~~ Yendolipin (1 14) is Acq a new lipobetaine isolated from Neodilsea yendoana from C' Hokkaido Japan.lo6 HO )mH (1 15) (1 16) (102) 19PO-dihydro (104) HO" WrnH (1 03) 19,20-dihydro (105) R2 R1 flBr OH (106) R' = H; R2 = OH; 17,18-dihydro (107) R2 = H; R' = OH; 17,18-dihydro Zealand.lo7 Deacetyllaurencin (120) and prelaureatin (12 1) (108) R1 = H; R2= OH have been synthesized from laurediols using hydrogen peroxide (109) R2=H; R'=OH sodium bromide and a partially purified bromoperoxidase from L.nipponica.108 Ten halogenated monoterpenes (1 22)- (131) that are related to the antitumour metabolite halomon .. .. R' R2 BrF::j, (1 10) R2 = H; R' = OH; 17,18-dihydro (1 11) R' = H; R2 = OH; 17,18-dihydro (112) R' = H; R2 = OH OH OH CI CI CI CI C13H27 +OH (122) (1 23) OH HNKC24H480 (113) Br CI Br% Br (124) CI (1 25) Ow0 c'%l Br CH2CI NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER * CHO CH2COOMe c,*r Br CI (132)lo9were isolated from specimens of Portieria hornemannii collected in different geographical locations the cytotoxicity profiles of compounds (127>(129) are the same as that of halomon (1 32).llo Viridianol (1 33) is an unusual rearranged sesquiterpene from Laurencia viridis.l" The structure of a sesquiterpene in the brasilane series from L. implicata112has been revised from (134) to (135) as a result of total synthesis of three isomeric Br (1 33) OH OH (1 34) (1 35) A new sesquiterpene ether dactyloxene D (136) has been reported from L. obtusa from the Gulf of Suez.114 The structure and stereochemistry of 3,4-epoxypalisadin A (137) from L. JEe~ilis~~~ was determined by an X-ray crystallographic study.l16 The structure of palisadin B (138) obtained from a Chinese Br@@ Almazoles A (142) B (143) and C (144) and prealmazole C (145) are alkaloids from a Senegalese red alga of the family Delesseriaceae that probably belongs to the genus Haraldiophyllum.122.123A major metabolite of Dasyapedicellata is the blue-green pigment isochlorin-e (146) which had not been reported previously from a natural ~0urce.l~~ The structures of (142H146) were elucidated by interpretation of spectral data.The 2-acyl pyrroles (147) and (148) which are metabolites of Gracilariopsis Zemaneif~rmis,'~~ have been synthesized and the absolute configuration of (148) thereby established.126 Additional syntheses of the anthelminthic agent from Digenea ~implex,'~'~ 12* (+)-a-kainic acid (149)129 and (-)-a-allokainic acid (1 5O)l3O have been reported.(142) R = CHO (143) R=H specimen of L. kurlae but originally isolated from L.JEexili~,~" was likewise confirmed by X-ray diffraction analysis.118 (-)-Filiformin (1 39) which is a metabolite of L. Jilif~rrnis,~~~ has been synthesized in an enantiocontrolled manner.120 OH OH Peyssonols A (140) and B (141) are rare sesquiterpene hydroquinones from a Red Sea Peyssonnelia sp. that inhibit HIV reverse transcriptase.121 6 Sponges Research on sponge metabolites continues to expand at a faster rate than for other phyla and also provides many of the most interesting marine natural products. There have been several analytical studies of sponge lipids but these are considered outside the scope of this review.Oceanapins A-F (1 5 I)-( 156) OH R' HO-HNyYxy 0 R2 (151) n=9; m=17; R'=H; R2=Me (152) n=9; m=17; R1=R2=Me (153) n=9; m=18; R'=Me; R2=H (154) n= 10; m= 17; R' = R2 = Me (155) n=10; m=17; R'=Et; R2=H (156) n=10; m=17; R'=Et; R2=Me from a New Caledonian specimen of Oceanapia cf. tenuis are unusual ceramides that contain branch-chained sphingosine and fatty acid residues.131 The stereochemistry of the crasserides which are metabolites of Pseudoceratina crassa exemplified by (157) was established by application of the Mosher method.lZ2 Longiside (1 58) which was found in large OH C6H13 0 (157) 0 amounts in Agelas longissima from the Bahamas is a digalactosyl ceramide with one galactose in the unusual /3-furanose form.Two new glycophospholipids axiceramides A and B which are mixtures of acyl chain homologues exemplified by the major components (159) and (160) respectively were isolated as their peracetates from a La 0 NATURAL PRODUCT REPORTS. 1996 Reunion species of A~ine1la.l~~ Erylusamines A-E (1 6 1)-( 165) are IL-6 receptor antagonists that were isolated from a Japanese specimen of Erylus placenta. 135 The antitumour and immuno- stimulatory constituents of Agelas muritianus ( = mauritiana ?) from Okinawa were identified as glycosphingolipids called agelasphins AGL-10 (1 66) and AGL- 12 (1 67) were the major components and six additional components AGL-7a (168) AGL-7b (a mixture) AGL-9a (169) AGL-9b (170) AGL-11 (171) and AGL-13 (172) were also described.136 The absolute configuration of the agelasphins was deduced by the total synthesis of AGL-9a ( 169)136 and AGL-9b (170).13' OAc AcOd R20 (161) R1=C3H7; R2=H (162) R' = -CH&H(CH&; R2 = H (163) R' = -CH,CH(CH& R2 = AC (164) R' = C4H9; R2 = AC (165) R' = C5H11; R2 = AC 'N ;iR OH OH (1 66) R = C22H45 (167) R = C23H47 0 The cytotoxic constituent of Hymeniacidorz hauraki from New Zealand was identified from spectral data as (82,11Z,14Z,17Z)-3,6-epoxyeicosa-3,5,8,11,14,17-hexaenoic acid (1 73).'" Five acetylenic acids (1 74)-( 178) identified as the COOH (159) R' =OH; R2 = H (160) R'=H; R2=OH NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER (176) R= OH (177) R=OMe corresponding ethyl esters were obtained from a specimen of Phakellia carduus obtained from a depth of 350 m by tra~1ing.l~’ Corticatic acids A-C (179)-( 181)are antifungal acetylenic acids from Petrosia corticata from Japanese Four new polyacetylenes (1 82H1 SS) ffom a Japanese Petrosia sp. are toxic to brine shrimp and inhibit cell division in fertilized ascidian eggs.141 Spectroscopic analysis has resulted in a (186) m+n=13 COOH OH (178) tentative structure for nepheliosyne A (186) from an Okinawan sponge of the genus Xestospongi~.~~~ The validity of determining the absolute configuration of enynols (allylic alcohols with an acetylene adjacent to the alcohol) by the exciton chirality method has been questioned :143 the absolute stereochemistry of the petroformynes exemplified by petroformyne 1 (187) was determined using Mosher’s method.144 The cytotoxic macrolide dictyostatin 1 (188) was isolated from a Spongia species from the Maldives and its structure without stereochemistry was elucidated by analysis of spectral data.145 Two trace cytotoxic constituents of Spirastrella spinispirulifera spongiastatins 8 (1 89) and 9 (1 90) which are NATURAL PRODUCT REPORTS 1996 are potent cytotoxic macrolides from the New Caledonian sponge Reidispongia coerulea their stereochemistry like that of similar macrolides remains undetermined.151 The structure and absolute stereochemistry of superstolides A (197) and B (198) NHAc -0 0 1’ OAO /vf’ (189) R= H (190) R=CI monoacetate derivatives of spongiastatins 7 and 5 respect-i~ely,~~~.14’ are potent inhibitors of glutamate-induced tubulin polyrnerizati~n.’~~ The absolute stereostructures of altohyrtins A-C (191)-(193) and desacetylaltohyrtin A (194) which are cytotoxic metabolites of Hyrtios altum from Okina~a,‘~~ have been determined by application of a combination of spec- troscopic rnethods.l5* Reidispongiolides A (195) and B (196) OH OH (191) R’= CI; R2 = AC (192) R’ = Br; R2 = Ac (193) R’ = H; R2= AC (194) R’ = CI; R2 = H 0 OMe OR OMe (195) R=Me (196) R=H which are potent cytotoxic macrolides from the deep water sponge Neosiphonia superstes from New Caledonia were elucidated by spectroscopic 153 Lasonolide A (199) which was identified by interpretation of spectral data is a potent cytotoxic macrolide from the Caribbean sponge Forcepia SP.’~~ The structures of theonezolides B (200) and C (201) OH (200)n=3 (201) n=7 NATURAL PRODUCT REPORTS 199CD.J. FAULKNER which are metabolites of a Japanese specimen of Theonella sp. were elucidated again without stereochemistry except at one centre by spectroscopic A new member of the halichondrin group isohomohalichondrin B (202) has been isolated from the New Zealand deep-water sponge Lisso-dendoryx SP.'~~ A structure-activity study of swinholide A (203) which is a cytotoxic agent from Theonella ~winhoei,'~~ and some analogues produced by acid treatment has been presented.15s The first syntheses of swinholide A (203) and (-)-preswinholide A (204) which are respectively major and minor metabolites of T.swinhoei,l5'*159 have confirmed the structures of the macrocyclic cytotoxin and its presumed biosynthetic precursor.16o* 161 ?Me yvo.... 87 Three new cytotoxic peroxylactones plakortolides B (205) C (206) and D (207) were obtained from Plakinastrella onkodes which was collected by dredging in the Gulf of Mexico,162 and Ph 0 H (205) R=H (207) R=Me Ph A.0 0 H (206) two cytotoxic peroxy acids (208) and (209) were isolated from a Papua New Guinea Callyspongiu species.lC3 An Okinawan I'hkortiS SP. previously reported to contain untenone A +'3/r Ox0 *.-,COOH o.o ...,C~ (208) (209) (210)164 and perhaps other compounds is the source of a tyramine-containing alkaloid plakoridine A (2 1l).165 Untenone A (210) has been synthesized in racemic form in five steps.166 As the result of conformational analysis of compounds of the xestospongin/araguspongine family the stereostructures of araguspongines B and E which are metabolites of an Okinawan Xestospongiu sp.,16' were reassigned from (212) to (213) and from (214) to (215) respectively.16* Haliclona exigua from the OMe t 4%.Andaman Islands contained 3a-methylaraguspongine C (2 16) together with known compounds in that series.169 Two symmetrical bis-quinolizidone alkaloids ( + )-xestospongin A/( +)-araguspongine D (21 7) from Xestospongia spp.170 and petrosin (2 18) from Petrosia serata,171 have been 173 Pokepola ester (219) which showed mild anti-HIV activity is an unusual phosphate diester from Spongia Oceania from Maui (Hawaiian Islands).174 A South African specimen of Jaspis digonoxea contained known compounds of 0 (219) the bengamide series together with digonazole (220) and cyclo(L-prolinyl-L-tyrosine) (22 I).175 Additional syntheses of bengamide E (222) and bengamide B (223) both of which are 0 n 0 HOfl$ 0 (221) NATURAL PRODUCT REPORTS 1996 metabolites of a Fijian Jaspis SP.,'~~ 17' The were pre~ented.'~' symmetrical alkaloid papuamine (224) which was obtained from a Pacific Haliclona SP.,'~~ has been synthesized by two research groups.180 18' A two-sponge association consisting of a thin crust of a Haliclona sp.overlaying an unidentified choristid sponge (which does not appear to be a Jaspis sp.) contained haliclonadiarnine (225) and papuamine (224) which are typical H H H&c.N& H metabolites of the Haliclona ~p.,"~.'~~ and two enol sulfates (226) and (227) which were presumed to be from the choristid ~p0nge.l'~ The enol sulfates were also found as the sodium salts jaspisin (226) and isojaspisin (227) and (E)-and (a-narains (228) and (229) from Japanese specimens of Jaspis sp. the H0r0So3-R HO (226) R=Na+ (227) R=Na+ (228) R = Me2NC(NH2)NH2+ (229) R = Me2NC(NH2)NH2+ jaspisins inhibited hatching of sea urchin embryos and the narains induced metamorphosis in ascidian lar~ae.'~~-~~' Four 3,4-dihydroxystyrene sulfate dimers (230)-(233) were also isolated from the same Jaspis sp.lS7 (222) R' = R2= H (223) R' = OCOC13H27;R2= Me NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER Tedanalactam (234) is a simple 8-lactam from Tedania ignis from the Florida Keys.lS8 An Ircinia sp. from Okinawa contained the indole alkaloid konbamidin (235) the structure of which was confirmed by ~ynthesis.'~~ An Okinawan Aplysina HN-COOH H (234) (235) sp. contained isoplysin A (236) and D-6-bromohypaphorine (237) :lgo L-6-bromohypaphorine was previously reported from Pachymatisma johnstoni.lgl 6-Bromoaplysinopsin (238) which is a metabolite of Smenospongia a~rea,~~~ was synthesized in a straightforward manner.lg3 The absolute configurations of Me Me herbindoles A (239) B (240) and C (241) which are metabolites of an Axinella sp.from Western and cis-trikentrin A (242) trans-trikentrin A (243) cis-trikentrin B (244) trans-trikentrin B (245) and iso-trans-trikentrin B (246) which were 89 two isomeric antifungal tryptophan dimers hamacanthins A (249) and B (25O).lg8(+)-Gellusines A and B both represented by (25 I) are diastereoisomeric tris-indole alkaloids from a deep-water New Caledonian sponge of the genus Gellius or BrJJ-qii.-J / N H H N Br Br Br 0rina.lgg Both ( f)-dragmacidin (252) and dragmacidon B (253) which are metabolites of Dragmacidin ~p.~'' and Hexadella SP.,~O~ have been synthesized by very different (240)R=Et (241)R = -CH=CHEt (€) (242) (252)R'=H; R2=Br; R3=OH (253)R' = Me; R2 = R3 = H Et / EtT routes.202 203 Nortopsentin D (254) which is an antifungal metabolite of Spongosorites ruet~leri,~~~ synthesized by was regioselective arylation of imida~ole.~~~ Four dimeric peptide alkaloids anchinopeptolides B-D (255)-(257) and cyclo-Et 0 (247)X = S (248)X=O all obtained from Trikentrion fEabellifarme,195 were established by synthesis combined with optical rnethods.lg6 Zyzzin (247) is HO a thiolactam from Zyzzya (Zyzza) massalis that undergoes rapid hydrolysis to the corresponding lactam (248) during purification.lg7The deep water sponge Hamacantha sp.contains 0 'H 0 (255)R' =Me; R2=H (256)R'=H; R2=Me (257)R' = R2= H anchinopeptolide C (258) which are metabolites of Anchinoe tenacior that were identified by spectroscopic methods bind to the somatostatin human B2 bradykinin and neuropeptide Y receptors.206 Phloeodictyon sp. from New Caledonia has yielded nine antibiotic and cytotoxic alkaloids phloeodictines Al-A7 (259)-(265) Cl (266) and C2 (267) the structures of which were elucidated by mass spectrometry and 2D NMR experi-ment~.~~' 4-Aminomimosamysin (268) and 7-amino-7-demethoxymimosamycin (269) are new isoquinoline alkaloids from an Indian Petrosia sp.208 (259)n= 7; m= 3;R =-CH2CH=CH2 (260)n= 7;m= 2;R = -CH2CH=CH2 (261)n = 5;rn = 3;R = -CH2CH=CH2 (262)n= 5; m= 2;R = -CH2CH=CH2 (263)n= 4;m= 3;R =-CH2CH=CH2 (264)n= 8; rn= 3; R = CHMe2 (265)n= 8; m= 2;R = CHMe2 (266)n= 7;rn = 3; R =-CH2CH=CH2 (267)n= 7;UI = 2; R = -CH,CH=CH 0 R' Me@: R2 0 (268)R' = NH2;R2 = OMe (269) R'=H; R2=NH2 The Papua New Guinea sponge Auletta cf.constricta contains the cytotoxic agent milnamide A (270) which is a highly Two methylated tripe~tide.~~~ new cytotoxic peptides hemiasterlin (271) which is closely related to milnamide A NATURAL PRODUCT REPORTS 1996 (270) and geodeamolide TA (272) were isolated together with the known compound jaspamide (273),210. 211 from Hemiasterella minor from South Africa.212 Two additional total syntheses of jaspamide (273) and one of geodiamolide A (274) which is a cytotoxic metabolite of Pseudaxinyssa have been 215 A total synthesis of cyclothonamide B OH (272)R=Pr' (274) R=Me (273) (275) which is a serine protease inhibitor from a Japanese Theonella sp.,216 has been The absolute stereo- chemistry of arenastatin A (276) which is a potent cytotoxic (275) cyclic depsipeptide from Dysidea arenaria,218 was established on the basis of spectroscopic and synthetic Microsclerodermins A (277) and B (278) are antifungal cyclic Meo4H 0 (277)R = OH I (271) (278)R = H NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER peptides from the New Caledonian deep-water lithistid sponge Microscleroderma sp. that contains symbiotic filamentous bacteria.222 Phakellistatin 3 (279) and isophakellistatin 3 (280) are cyclic heptapeptides containing isomeric photo-Trp units that were isolated from Phakellia carteri from the Comoros Islands the structure of isophakellistatin 3 (280) was de-termined by X-ray analysis.223 Phakellistatins 5 (281) and 6 Ho'*8 (279) Ph (282) are additional cytotoxic cyclic heptapeptides isolated from Phakellia costata from Chuuk (Tr~k).~~~ 225 An Axinella sp.from Palau contained two additional cytotoxic cyclic heptapeptides axinastatins 2 (283) and 3 (284),226 and the cyclic octapeptide axinastatin 5 (285) was isolated from Axinella cf. An Australian specimen of carteri from the Com~ros.~~' (283) R=Me (284) R =Et Theonella sp. contained perthamide B (286) which is a cyclic octapeptide.22s Discobahamins A (287) and B (288) are antifungal cyclic peptides from a deep-water specimen of Discoderrnia sp.from the Bahamas.229 An Okinawan species of Hymeniacidon has yielded four additional cyclic octapeptides (287) R=H (288) R=Me NATURAL PRODUCT REPORTS 1996 hymenamides G (289) H (290) J (291) and K (292).230 of a bicyclic dodecapeptide with an arabinose residue attached Theonegramide (293) is an antifungal glycopeptide consisting that was obtained from a Philippines specimen of Theonella ~winhoei.~~' Theonellapeptolide IId (294) which prevents fertilization of sea urchin eggs is a cyclic tridecapeptide lactone from an Okinawan specimen of T.~winhoei.~~~ Four additional cytotoxic and antimicrobial tetradecapeptides discodermins E-H (295)-(298) were isolated from the Japanese lithistid sponge Discoderrnia kiiensis; the sequence of amino acid residues in discodermins A-D (299H302)233was revised by (293) n3 CONHZ OH I (295) R'=R2=H; R3=R4=Me; R5=b (296) R' = R2= H; R3 = Me; R4= Et; R5= a a = (297)R' = R3= R4 = Me; R2= H; R5 = a NATURAL PRODUCT REPORTS 1996D.J. FAULKNER reversing the positions of threonine and asparagine from their original assignment. 234 235 Polytheonamides A-C are highly cytotoxic polypeptides that have the N-terminus blocked by a carbamoyl group. 236*237 Cyclostellettamines A-F (303H308) are dimeric cyclic pyridinium salts from a Japanese sponge Stelletta maxima that inhibit binding of methyl quinuclidinyl benzilate to muscarinic acetylcholine The total synthesis of (f)-ikimine A (303)m=5; n=5 (304) m=5; n=6 (305) m=6; n=6 (306) m=5; n=7 (307) m=6; n=7 (308) m=7; n=7 (309) which is a 3-alkylpyridine from an unidentified Micro- nesian sponge,239 has confirmed and clarified the structural elucidation.240 The tetracyclic alkaloid halicyclamine A (3 10) (309) from an Indonesian Haliclona sp.appears to be derived from a dimeric pyridinium -precursor.241 The Papua New Guinea sponge Xestospongia ingens has yielded the cytotoxic alkaloids ingenamine (311) ingamines A (312) and B (313) and OH (313) X= H madangamine A (314) all of which appear to be related bios ynthetically .242-244 The structure of xestocyclamine A which is a PKC inhibitor from a Papua New Guinea Xestospongia sp.,245has been revised from (315) to (316) and a new homologue xestocyclamine B (3 17) has been OH (317) An undescribed species of Pachypellina from Indonesia contains the cytotoxic alkaloid 8-hydroxymanzamine A (318).247Two new alkaloids 1,2,3,4-tetrahydro-2-N-methy1-8-hydroxyman-zamine A (3 19) and 1,2,3,4-tetrahydr0-8-hydroxymanzamine A Me' (320) were obtained from Petrosia contignata and (3 19) was also found in Cribrochalina sp.both from Papua New Guinea.24sA number of new compounds have been reported from Amphimedon sp. from the Kerama Islands Okinawa but it is not clear whether one or more species are involved. Ircinols A (321) and B (322) are antipodes of previously reported -4OH NATURAL PRODUCT REPORTS 1996 rnan~amines,~~~ keramaphidin B (323) is considered to be a plausible biogenetic precursor of manzamine alkaloids,250 as are keramaphin C (324) and keramamine C (325),251 and 6- hydroxymanzamine A (326) and 3,4-dihydromanzamine A /=AoH HN (327) are new members of the manzamine family.252 The structures of all of the compounds (3 10)-(327) in the manzamine series were elucidated by interpretation of spectroscopic data.Two simple pyrroles pyrrole-2-carboxamide (328) and N-formylpyrrole-2-carboxamide (329) were obtained from Agelas oroides from the Great Barrier Reef.253 The Fijian sponge (328) R= H (329) R=CHO Agelas mauritiana contains mauritamide A (330) and two related members of the oroidin series.254 The absolute con- figuration of agelastatin A (331) which is a metabolite of A.dendrorn~rpha,~~~ was determined by application of the exciton coupling method to a derivative.256 A highly efficient synthesis Me of (+)-hymenin (332) which is a potent a-adrenoceptor blocker from Hymeniacidon SP.,~~' involves coupling of a bicyclic intermediate with 2-arninoimida~ole.~~~ NZH2 Br4 0 (332) New bromotyrosine-derived metabolites continue to be found in verongid sponges. These include four simple trimethyl- ammonium salts (333)-(336) from a Bahamian specimen of coo-(333) R = H; X = Br (334) R=Me; X=Br (335) R=Me; X=H (336) R =H;X=H Pseudoceratina cras~a.~~~ Psammaplysilla purpurea from the Bay of Bengal contains two related metabolites (337) and (338).260 Three brominated and iodinated tyrosine derivatives (339)-(341) were isolated from a Bahamian specimen of Iotrochota birotulata.261 Br MeO (337) X = H (338) X = Br (339) X =Y = Br (340) X =I;Y = Br (341) X=Y=I Twelve bromotyrosine derivatives were isolated from a Bahamian specimen of Aplysinafistularis f.fulva but only two of these (342) and (343) were new; a simple histidine derivative (344) was also obtained.262 Similarly of eleven metabolites isolated from a Bahamian Verongula sp.only the two simple OMe OMe 0 0 0 (342) 124.3 (331) (343) 12-a NATURAL PRODUCT REPORTS 1996D. J. FAULKNER salts (345) and (346) had not been reported previously.2s3 Verongamine (347) itself a histamine derivative was isolated from a deep-water specimen of Verongula gigantea as a histamine-H antagonist.264 Two additional bastadins 16 (348) OMe HOON (347) and 17 (349) have been obtained from Ianthella basta from Sulawesi Indonesia.265 During a search for inosine 5’-phosphate dehydrogenase inhibitors a Papua New Guinea specimen of Ianthella basta yielded six known bastadins together with bastadin 18 (350).266 All of the bromotyrosine derivatives were identified by interpretation of spectroscopic data.The brominated diphenyl ether (351) from Dysidea spp.267has been synthesized in an interesting manner.268 R NOH NOH (348) R =H; X=Br (349) R =OH; X=H The antimicrobial constituent of an Australian Spongosorites sp. was identified as the simple alkaloid (352).26g A four step iminophosphorane-mediated synthesis of leucettamine B (353) from the calcareous sponge Leucetta mi~roraphis~’~ has been The antifungal constituents of a Japanese U 0 Halichondria sp.were identified as tryptophol (354) phenyl- acetamide and the known272 bacterial metabolites 6-bromoindole-3-carboxaldehyde indole-3-carboxaldehyde and p-hydr~xybenzaldehyde.~’~ Two minor constituents of the Mediterranean sponge Anchinoe tenacior are the tripeptide H (354) (355) and the sulfone (356).274 Lamellarins 0 (357) and P (358) were isolated from Dendrilla cactos that was obtained by dredging off southern The structure of phorbazole (355) 02 (356) HO (357) X = H (358) X=OH A (359) which was isolated from the South African sponge Phorbas aff.clathrata was determined by X-ray analysis and those of phorbazoles B-D (360)-(362) were established by R4 (359) R’ = H; R2 = R3 = R4 = CI (360) R’ = R2 = R3 = CI; R4 = H (361) R‘ = R4 = H; R2 = R3 = CI (362) R’ = R2 = R4 = H; R3 = CI comparison of spectral data.276 Variolins A (363) and B (364) and N(3’)-methyltetrahydrovariolin B (365) were isolated from the Antarctic sponge Kirkpatrickia varialosa. The structures of variolin B (364) the most cytotoxic of the three and variolin A (363) were determined by X-ray analysis and the structure of (365) was elucidated by analysis of spectroscopic data.*”. 278 y2 y42 A N’ N OH (365) Discorhabdin E (366) is an additional alkaloid from Latrunculia cf.bocagei from New Zealand that appears in a paper discussing the cytotoxicity of the dis~orhabdins.~’~ Discorhabdin C (367) from Latrunculia batzelline C (368) and isobatzelline C (366) X= H (367) X =Br (369) from Batzella SP.,~~~ and makaluvamines A-E (370)-(374) from Zyzzya massallis (= cf. marsailis)282were all synthesized using a similar ~trategy.~~~-~~~ synthesis of A second makaluvamine D (373) employed a very different strategy.286 Me@NH2 CI (369) (370) Me@NH2 +‘Me NATURAL PRODUCT REPORTS 1996 Damirones A (375) and B (376) which are metabolites of Damiria SP.,~~’ were synthesized from a quinoline precursor.288 A purine base 1-methylherbipoline (377) was obtained from a (377) (375) R=Me (376) R = H Japanese Juspis SP.,~” and zarzissine (378) which is a 43- guanidinopyrazine base was isolated from the Mediterranean A sponge Anchinoe pauperta~.*~~ sponge of the order Hadromerida family Tethyidae contained 2’-deoxyspongosine (379) together with the known291 metabolite spongosine (380).292 The unusual red pigment trikendiol (381) which was (378) HOW HO R (379) R =H (380)R=OH &..OH /.isolated from Trikentrion loeve from Senegal is an inhibitor of HIV-1.293 A new synthesis of the pigment fascaplysin (382) which is a metabolite of Fascaplysinopsis sp.,294 has been The porphyrin pigments corallistins B-D (383)-(385) which occur in remarkably high amounts in a New Caledonian Corallistes SP.,*~~ have been & /N HO (32) (383) R’ = R2 = Et; R3 =COOMe; R4 =H (384) R’ =Et; R2= H; R3=COOMe; R4=H (373) (385) R’ =Et; R2 = H; R3 = R4 =COOMe NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER 97 The Australian sponge Thorecta choanoides contained a new nakijiquinone A (393) together with nakijiquinone B (394), sesquiterpene quinone (386) and the corresponding hydro- was isolated from an unidentified Okinawan sponge.305 An quinone (387).298 An X-ray crystallographic study of avarol efficient synthesis of ( & )-mamanuthaquinone (399 which is a Me0 0 (386) OH (387) (394) (388) which is a biologically active metabolite of Dysidea / OMe a~ara,~~~ confirmed the well established The metabolites of Reniera mucosa from Spain include six known members of the panicein family and two new sesquiterpene HoQoH (395) cytotoxin from a Fijian Fasciospongia SP.,~O~ has been Hyatellaquinone (396) was obtained from Hyatella (388) intestinalis from South Africa.l" The fact that the epimeric hydroquinones renierins A (389) and B (390).301 The synthesis OMe of racemic metachromin-A (391) which is a metabolite of was Hippospongia rnetachromi~,~~~ accomplished by a con-vergent The structure of glycinylilimaquinone ox OH (389) (396) 0 dactyltronic acids (397) and (398) were isolated from a Malaysian specimen of Ductylospongia elegans together with ilimaquinone and related sesquiterpene quinones suggests that MeoH otl they arise by oxidation of a sesquiterpene quinone precur~or.~*~ The isomeric methylene quinones corallidictyals A (399) and B (390) 0 (392) a cytotoxic metabolite from a specimen of Fusciospongia sp.from the Philippines was elucidated by analysis of spectral data and confirmed by An isomeric compound (397) H 0 (392) (398) (399) 98 (400) are protein kinase C inhibitors from the Bahamian burrowing sponge Aka (= Siphonodictyon) orall lip hag urn.^^^ (-)-Prehalenaquinone (401) was synthesized as a putative bio- synthetic precursor of halenaquinone (402) and was subse- quently .isolated from Xestospongia sapra from Okina~a.~'~ A Coscinoderma sp. from the Great Barrier Reef contained the sesterterpene quinone coscinoquinol (403).311 Three new hepta- CHO HO 0 (403) prenylhydroquinone derivatives (404)-(406) were obtained from an Indian specimen of Ircinia fa~ciculata.~'~ 2-Tetraprenylbenzoquinol (407) which is an analgesic from Irciniu ~~~uscuYu~,~~~ has been synthesized from farnesol and a prenylated hydr~quinone.~~~ HO (CJ-JW An Indian Ocean sponge identified as a new Axinella sp.surprisingly contained two new furanosesquiterpenoids axinellin-A (408) and axinellin-B (409) and 3,5-dibromo-4- methoxyphenol (410) a known315 metabolite of a verongid OMe BrQ*r OH NATURAL PRODUCT. REPORTS 1996 sponge.316A new sesquiterpene (41 1) was isolated from an Indian Ocean specimen of Dysidea herbacea and its structure was confirmed by synthesis from a known sesquiterpene f~ran.~~~ In a paper describing the determination of absolute configuration of members of the furodysin and furodysinin families two new furanosesquiterpenes (412) and (413) were hw 00 H AcO q (413) described.318 Upial(414) which is a metabolite of D.fragili~,~l~ has been synthesized from ~-mannitol.~~' A new approach to the synthesis of (f)-euryfuran (415) a metabolite of Euryspongia employs a [3,3]-sigmatropic rearrange- ~ent.~~~ The sesquiterpene isothiocyanate (416) from Trachyopsis ( = Axinyssa) aplysinoide~~~~ was synthesized using an oxidative radical cyclization reaction as the key A of (-)-(10R)-10-isothiocyanoaromadendrane(417) '0 (415) (41 4) (417) indicated that it was the enantiomer of epipolasin B which was isolated from Epipolasis kushirnotoensi~.~~~ Axamide- 1 (418) and axisonitrile-1 (419) which are metabolites of Axinella ca~nabina,~~' have been synthesized using an intramolecular Michael addition as the key reaction.328 (418) X = NHCHO (419) X=-NC NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER Six diterpene isonitriies 10-epi-isokalihmols F (420) and H isolation procedure was obtained from an Indian Ocean Four new diterpenoids (421) 1-epi-kalihinene (422) 15-isothiocyanato- l-epi- specimen of Fasciospongia cavern~sa.~~~ kalihinene (423) 1,lO-diepi-kalihinene (424) and kalihipyran 12-deacetylaplysillin (434) 15-hydroxy-ent-isocopal- 12-en- 16-a1 (439 15,17-diacetoxy-ent-isocopal-12-en- 16-a1 (436) and H‘- CN HO (420) R=-NC (422) R = -NC (421) R = -NCS (423) R=-NCS n. “f.C (424) (425) were isolated from a specimen of Acanthella cavernma from the Seychelles.329 Two of these compounds were also reported as kalihinene-A (424) and kalihinene-B (422) from the same sponge collected in the same general location although (424) was found to be racemic in this A.cavernosa 15,liT-diacetoxy- 1 1-oxo-ent-isocopal- 12-ene (437) were iso-lated together with seven known compounds from an Italian OH OAc P b Ac (434) OAc OAc (435) R’ = R~= (437) H (436)R’ = Ac; R2 = OAC specimen of Spongia zi~zocca.~~~ The structure and absolute configuration of blanesin (438) a furanoditerpene from a Spanish specimen of Raspaciona aculeata has been Seven new furanoditerpenes (439)-(445) and a sesterterpene OR (439) R=H (425) (440)R=Ac from Fiji yielded seven new diterpenes (426)-(432) most of which are formamides together with known metabolite^.^^' A trisnorditerpene (433) which is probably an artifact of the R2.-.o& R’ OH (441) R‘ =OH; R2 = H H _.-(442) R’ = H; R2=OH & qR2 (426) R’ = NHCHO; R2 = -NC (429) R1 = (427) R’ = -NC; R2 = NHCHO (430) R’ = (428) R‘ = R2 = NHCHO (431) R’ = (432) R’ = R2 = -NC -NC; R2 = NHCHO NHCHO; R2 = -NC NHCHO; R2 = -NCS Ri@ 0 OH (443)R’ =H;R~=OH (444)R’=OH; R2=H (446) were isolated from a Western Australian species of Spongia two of the diterpenes (439) and (440) were obtained as 3 1 mixtures of enantiomer~.~~~ (-)-Reiswigin A (447) which is an antiviral diterpene from Epipolusis reis~igi,~~~ has been synthesized in a stereoselective manner.337 HOOC (447) A reinvestigation of the structure of strobilinin originally isolated from ircinia ~trobilina,~~' revealed that it consisted of two geometrical isomers (448) and (449).33s The absolute OH > 'I 0 (448) OH configuration of the known ircinia metabolite variabilin (450)340 was established by degradation while those of ircinin-l(45 1),341 ircinin-2 (452)341 and strobilinins (448) and (449) have been OH OH tentatively assigned.342 The absolute configuration at C-4 of manoalide (453) and related compounds isolated in this instance from Hyrtios erecta was determined using the Horeau and Mosher methods.343 Two syntheses of manoalide (453) NATURAL PRODUCT REPORTS 1996 which is an antiinflammatory agent from Luflariella v~riabilis,~~~ have been as have syntheses of (a-neomanoalide (454) and (3-neomanoalide (455),346 which are 0 'OH (454) 0 (455) also from L.~ariabilis.~~' The structure of palauolide (456) which was isolated from a mixture of sponges but is now known to be from a Fasciospongia species,348was confirmed by Fasciospongides A (457) B (458) and C (459) are HOgo HO HO II (456) (457) 0 new oxidized manoalide derivatives from a New Caledonian Fasciospongia species.35oCacospongia linteiformis from the Bahamas contained cyclolinteinone (460) lintenolide A (461) do HO (461) R=Ac (453) (465) R = -COCH(OH)Me NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER and lintenolide B (462) all of which are ichthyotoxic and sponge Corticium sp.358Aragusterols B (473) C (474) and D Spongianolides A (463) B (464) C (475) are additional cyclopropane-containing sterols from a inhibit fish feeding.351*352 Xestospongia sp. from The structure of the cytotoxic sterol aragusterol C (474) was determined by X-ray (462) R=Ac (466) R = -COCH(OH)Me (463) R=Ac (464) R = -COCH(OH)Me (461) D (462) E (465) and F (466) are cytotoxic sesterterpenes from a Spongia species from Florida spongianolides C and D were assigned the same structures as lintenolides A and B respectively.353Two sesterterpene acetals (467) and (468) which are probably identical to incorrectly identified artifacts were obtained from l~ffolide,~~~ obtained from a New Caledonian Dactylospongia sp.the structure of (468) was determined by X-ray analysis.355The Mediterranean sponge Cacospongia mollior contains 12-deacetoxyscalaradial (469) as a minor metabolite.35612-epi-Heteronemin(470) was shown to be a major metabolite of a New Caledonian specimen of Hyrtios ere~ta.~~’ Lokysterolamines A (471) and B (472) are antibacterial steroidal alkaloids that were obtained from the Indonesian 0- (473) OH c w d3M 0 (474) analysis.359Aragusterol D (475) is identical to xestokerol C which was previously isolated from an Okinawan Xestospongia sp.361and reported without stereochemistry at C-25 and C-26. Three new 3P-methoxy sterols (476)-(478) were isolated from (475) (477) OH (471) R = NMe2 (472) R=NHAc Micruscleroderma spirophora from The structure and absolute configuration of bisconicasterone (479) from a Japanese specimen of Theonella swinhoei has been determined by X-ray crystallography and Mosher’s method.363 An Okinawan Tupsentia sp.contained five antimicrobial 14-methyl NATURAL PRODUCT REPORTS. 1996 vitr~.~~~ Ophirapstanol trisulfate (488) from the deep-water sponge Tupsentia ophiraphidites exhibited inhibition in the guanosine diphosphate/G-protein RAS exchange assay.366 Ten highly hydroxylated 9,ll -secosteroids (489k(498) with anti- histaminic activity have been found in Euryspongia sp. from Na03SO*0w 0SO3Na (488) sterol sulfates topsentiasterol sulfates A-E (480H484).364 Halistanol sulfates F-H (485)-(487) are three additional sterol sulfates from Pseudoaxinissa digitata that inhibit HIV in R’ b= -(489) R’ =OH; R2= H; R3=a (490) R‘ = OH; R2 = H; R3 = b C= ...+ (491) R’ = OH; R2 = H; R3 = c (492) R‘ = OH; R2 = H; R3 = d (493) R‘ =OH; R2= H; R3=e (494) R1 = H; R2 = OH; R3= a (495) R’ = H; R2= OH;R3= b (496) R’ = H; R2 = OH; R3 = c (497) R1 = H; R2 = OH; R3 = d (498) R’ = H; R2= OH; R3= e New Caled~nia.~~’ Stellettasterol (499) is an antifungal 9,ll- secosterol from a Japanese species of Stelletta.368The 9,ll- secosterol (500) isolated from the Mediterranean sponge HO< NaO&O**W OH OS03Na HO (484) OH (499) Na03S0rt-cfs (500) Spungia uficinalis is a further example of a highly oxidized sterol from this source the proposed structure was confirmed (485)R=.-.+ by synthesis.36g Hapaioside (501) is a 19-norpregnane glycoside Mn (487) R==.& .MIIE 103 NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER containing a 6-deoxy sugar from a specimen of Cribrochalina olemda from Pohnpei Microne~ia.~'~ go$ $5 Erylus forrnosus from the Bahamas contains a major triterpene tetrasaccharide formoside (502) in which the methyl H group at C-14 is oxidized to a carboxylic a~id.~" The Bahamian sponge E. gofrilleri contains eryloside E (503) which is a ;OAc OR2 :OR' ;OR2 (508) R' = H; R' = AC (509) R' = R2= H (511) R' =Ac; R2=H (510) R' = Ac; R' = H (512) R' = H; R2 = AC class have been isolated from the Mediterranean sponge Raspaciona aculeata.374 Similar triterpenoids sodwanones A-F (513)-(5 18) were obtained from Axinella weltneri from South Stellettin A (519) is a triterpenoid pigment of the malibaricane type that was obtained from the Chinese sponge Stelletta tenui~.~'~ The structures of the steroids and tri-terpenoids were all elucidated primarily by analysis of spectroscopic data. % \HI I $q0$$ \\ .'R I (513) R =OH (51 5) (514) R=H 9 go% H o% Hb i HO i trisaccharide derivative of a similar triterpene in which one of (516) (51 7) the sugars is attached through an ester bond to the carboxylic acid group at C-14.372 Ulososide A (504) is a 14-nortriterpene disaccharide from a Ulosa sp.from Madagascar.373 Eight additional minor triterpenoids (505)-(5 12) of the raspacionin 0 OH I @OH0$ 0 H I (518) 7 Coelenterates The brominated fatty acids 6-bromoheneicosa-5,9-dienoicacid (520)and 6-bromodocosa-5,9-dienoic acid (521) were isolated from among the component fatty acids obtained from the phospholipids of the sea anemone Stoichactis heZianth~4.v.~~~ Br HOOC R (505) (506) R' = R2= H; R3=Ac (520) R = Ci 1H23 (507) R' = R2= Ac; R3 = H (521) R = C12H25 NATURAL PRODUCT REPORTS 1996 Seven new butenolides (522)-(528) were isolated together (533)-(536) the epoxides (537) and (538) (a-punaglandins 3 with the known butenolide ancepsenolide (529) from the (539) and 4 (540) and a number of 12-acetate Caribbean gorgonian Pterogorgia ~itrina.~~~ The S,S absolute configuration of (+)-ancepsenolide (529) which was isolated from the gorgonians Pterogorgia anceps and P.guadal~pensis,~~~ AcO..C02Me was determined by total Three unusual fatty acid 0 0 0 c'+ o m AcO 17 (522) n= 10 (525) n= 12 (533)(534) 17,la-dihydro AcO' (523) n= 10 17 (526) n= 12 (535) (536) 17,18-dihydro OAc 0 1 C02Me 0 cl-q (524) n= 12 HO 17 / (529) n= 10 (537) 0 0 (538) 17,18-dihydro 0 AcO.. GC02Me clq 0 0 HO 17 (539) (540)17,18-dihydro derivatives (530)-(532) were isolated from the Indian sea pen There were no reports of new sesquiterpenes from coelen- Virguluria sp.381A review of the punaglandins found in the terates during 1994 although synthesis of members of this class octocoral Telesto riisei from Hawaii briefly describes fifteen of metabolites continues to be popular.(-)-Clavukerin A new compounds in this series including punaglandins 5-8 (541) which is a metabolite of Clavularia k~ellikeri,~~~ was syn- thesized from (-))-~arvone.~~~ (i-)-Clavukerin A (541) and (+)-isoclavukerin A (542) were synthesized from a common 0 precursor.385 A synthesis of the 8R,11R enantiomer of precapnelladiene (543) which was obtained from Cupnella imbricut~,~~~ has been accomplished in six steps from (R)-(2- Me0 cyclopentenyl)methano1.387 The simplest of the tricyclic metabolites of C. imbric~ta,~~~ (-)-A9~12-capnellene (544) has 0 p3 (531) 0 Me0 OAc (532) ' (543) (544) NATURAL PRODUCT REPORTS 1996D.J. FAULKNER cytotoxic cembranoids (556)-(558) were obtained from a been prepared using silyl group directed stere~control.~~~ Syntheses of ( f)-curcudiol (545) ( f)-curcuhydroquinone Great Barrier Reef specimen of S. trocheliophorum and their (546) and ( +)-curcuquinone (547) which were obtained from Pseudopterogorgia rigid~z,~’~ have been The struc- tures of tubipofuran (548) and 15-acetoxytubipofuran (549) which were isolated from the Japanese stoloniferan coral Tubipora mu~ica,~’~ were confirmed by total (548)R=Me ‘ (547) (549)R=CH@Ac The chemistry of coelenterates continues to be dominated by reports of new diterpenes. An undescribed species of Lobo-phytum from the Indian Ocean contained (1 1Z)-2-epi-11-lobohedleolide (550) and (7R,8R)-epoxycembranolide (551) together with two known diterpene~.~’~ The methyl ether (552) obtained from Lobophytum strictum is probably an artifact of methanol extra~tion.~’~ Sarcotol (553) and sarcotol acetate (554) are cytotoxic cembranoids with a rearranged 13-membered ring system that were isolated from a Japanese species of S~rcophyton.~~~ A Chinese specimen of Sarcophyton trocheliophorum contained sartrochine (555).397 Three mildly (552) ‘.bOH (553) R=CH@H (554) R = CH@Ac structures including absolute configurations were elucidated by the application of spectroscopic methods.3ss The total (556) R=H (558) (557) R=Ac syntheses of ( _+ )-sarcophytol-M (559),39s which is a metabolite of the soft coral S.gla~cum,~~~ and (+)-sarcophytol A (560),401 also obtained from S. gla~cum,~O~ both employed linear sesquiterpene starting materials. A bicyclic diterpene diol(56 1) from an Indian Ocean specimen of S. trocheliophorum (misspelt as trocheliphorurn) was characterized as the corresponding The mon~acetate.~~~structure of mandapamate (562) an HO-‘ OMe MeOOC HA interesting tetracyclic diterpene isolated from Sinularia dissecta from Mandapam India was elucidated by interpretation of spectral data supported by a mechanistic hypothesis for its formation.404 Two new diterpenes (563) and (564) of the lobane class were isolated from a new species of Lobophytum from the Andaman and Nicobar Islands (Indian Ocean).4o5 Seven new cladiellane diterpenes (569457I) were isolated from the soft coral Cladiella australis from the Andaman and Nicobar Islands.406* 407 The hemolytic diterpenes litophynols A (565) R' = -COCH2CHMe2; R2 = Ac (566) R' = H; R2 = -COC3H7 (567) R'=Ac; R2=H (568) R = AC (569) R =H pQOAc (570) (571) stereoisomers (572) and B (573) were isolated from the mucus secreted by a Japanese soft coral of the genus Lituphyton; the structures were determined by interpretation of spectral data and the X-ray analysis of a simple derivative.408 Palmonine F (574) is a (573) (574) diterpene of the eunicellin class from the gorgonian Eunicella verrucosa from southern Spain.409 The Caribbean gorgonian coral Briareum asbestinum is one of the most exhaustively studied marine organisms.A specimen from Tobago contained NATURAL PRODUCT REPORTS 1996 five additional non-chlorinated briananes (575)-(579) together with a new asbestinane (580) containing an oxetane ring.410 The unusual secu-asbestinin (58 1) was obtained from a specimen of B. asbestinum from Mona Island411 and sixteen minor asbestinins (582)-(597) were isolated from collections made ""I \ COOMe COOMe (575) R = -COC3H7 (577) (576) R = H 0q-$ 0 OH 0 0 (578) (579) w *.*-0 OR (582)R = -COC7H15 (584) R = -COC745 (583) R = AC (585) R = -COC& (588) R=Ac .o (587) R = -COC7H15 (590) R=Ac w .... 0 OH (589) (592) R=Ac (594) (593) R = -COC3H7 NATURAL PRODUCT REPORTS 1996D.J. FAULKNER (595) (596) R=Ac (597) R = -COC3H7 around Puerto R~CO.~~~ The structures previously proposed for asbestinin-6 and a~bestinin-7~~~ revised from (598) to were (599) and (600) to (601) respectively.412 (598) R’ = -COC+-l~,; R2 = AC (599) R’ = Ac; R2 = -COC*I~ The Japanese gorgonian Acalycigorgia sp. contains acaly- cigorgins A-E (602)-(606) which are xenicane diterpenes that are toxic to brine shrimp and inhibit cell division in fertilized TMe 0 0 Meo& Ad ascidian eggs.414 Helioxenicins A-C (607H609) were obtained from two specimens of the blue coral Heliopora coerulea one from Okinawa and the other from the Great Barrier Reef; the structure of helioxenicin B (608) was determined by X-ray analysis.415 The soft coral Xenia faraunensis from the Red Sea 4 (607) R = H (608) R = AC has yielded three cytotoxic diterpenes xeniafaraurols A (610) and B (611) and faraunatin (612) that have unusual carbon ~keletons.~’~ Another new skeletal class of tricyclic diterpene is found in floridicin (613) which was isolated from a Japanese \ CHO specimen of Xeniaflorida.The structure of floridicin (61 3) was determined by X-ray analysis of a deri~ative.~~’ Palmatol(614) which was obtained from the Mediterranean octocoral Alcyonium palmatum is the first representative of yet another diterpene Lemnalia bournei yielded an interesting diterpene glycoside (615) in which the sugar is joined to a diterpene aldehyde through an acetal linkage.419 A number of polyhydroxylated sterols have been reported from soft corals from India (22E,24S)-24-methylcholesta-5,22-diene-3P,25-diol (616) was obtained from a Lobophytum I NATURAL PRODUCT REPORTS 1996 24-methylenecholest-4-ene-3~,6~-dioI (6 17) came from Sinuluriu ovispi~ulata,~~' 24-methylenecholestane-la,3/3,5a,6/3,1 la-pentaol (618) and the corresponding 11-five acetate (619) were isolated from S.dis~ecta,~~~new OH (627) R =\woH I OH I (628) R=\%oH I OH riI (618) R=H (619) R =Ac (630) ergostane derivatives (620)-(624) and cholestane- lP,3/3,5a,6P- tetraol (625) from a new species of Lobophyt~m,~~~ and four new (17E)-polyhydroxy-23,24-dimethylcholesta-7,17(20)-(631) R' =OH; R2= H (633) R' = H; R2 = OH I HOHO W OH (621) R' = H; R2 = Me; R3 =OH 8 (622) R' = H; R2 = Me; R3 = OAc (623) R' = OH; R2 = Me; R3 = OAc (624) R' =OH; R2=Me; R3=H 0 (625) R'=OH; R2=R3=H 0+OH .***u -'OH dienes (626)-(629) were found in S.rnayi.423 S. mayi from Japan contained 25-hydroxysarcosterol (630)424 and Litophyton OH (634) arboreum from China yielded 24-methylcholesta-5,24(28)-diene-3P,7P 19-triol(63 1) [the structure is incorrectly drawn in the Journal] and (24E)-24-ethyl-5a-cholesta-8,24(28)-diene-3P 12/3,19-triol (632).425 The soft coral S. gibberosa contained 24-methylenecholest-5-ene-3~,7~,16P-triol (633) and two ster- oidal glucosides (634) and (635),426 while S. hirta yielded 24- methyIenecholest-7-ene-3P,6a,9a, 1la-tetraol (636) and 24-methylenecholesterol-3-O-a-~-fucopyranoside(637).427 Two novel meroditerpenoids (638) and (639) were isolated from S.muyi. 28 OH (635) NATURAL PRODUCT REPORTS 1996-D. J. FAULKNER HO OH (636) HO OH HO.. OH ‘OH OH OH N H2 OH The final steps in the total synthesis of palytoxin (640) which was obtained The indole alkaloids villagorgins A (641) and B R’,@ from a toxic Palythoa sp.,429 have been briefly (642) from Villagorgia (= Villogorgia) r~bra,~~~ have been 0 synthesized in an efficient manner.432 N-f YY Br R2 OH Br LO (643) R’ = Br; R2 = Me (644) R’ = H; R2 = Me (645) R’ = Br; R2= H OMe 8 Bryozoans Br Chemical studies of bryozoans are few in number but often yield interesting brominated metabolites.Amathia convoluta from Florida contains very small quantities of convolutamines (647) A-E (643)-(647) and convolutamides A-F (648)-(653) some of which show cytotoxicity against P388 L1210 or KB cell 110 434 Two additional alkaloids flustramine E (654) and debromoflustramine B (655) were obtained from Flustra foliacea from the North Sea.435 In addition a reversible (654) (655) conversion of flustramine B N-l-oxide (656) into flustrarine B (657) has been A diastereoselective synthesis of ( +)-ent-debromoflustramine B ent-(655) has established the absolute configuration of the natural Four new x x bipyrrole alkaloids tambjamines G-J (658)-(66 l) which are toxic to brine shrimp have been isolated from Bugula dentata from It is not known whether the aldehyde (662) which can arise from base-catalysed dimerization of citral (663) is a true metabolite of Flustrafoliacea or an artifact.439 Br H NHR I (658)R=Et (659) R=Pr (660) R = -CH&H(Me)S (661) R = -CH,CH(Me)Et (662) UCHO (663) 9 Molluscs The majority of compounds isolated from marine molluscs are accumulated from dietary sources.The absolute stereo-chemistry of aplyronine A (664) which is a potent antitumour NATURAL PRODUCT REPORTS 1996 agent from Japanese specimens of the sea hare Aplysia k~rodai,~~~ has been determined by enantioselective synthesis of degradation The total synthesis of aplyronine A (664) was also The structure of doliculide (665) which is a cytotoxic cyclodepsipeptide from the Japanese sea hare Dolabella auricularia was elucidated by interpretation of spectroscopic data and confirmed by total Syntheses were reported for dolastatins 10 (666)446 and 15 (667),447both of which are cytotoxic agents from Indian Ocean specimens of D.auric~luria.~~~ An enantiocontrolled synthesis of (-)-aplysin (668) and (-)-debromoaplysin (669) which are metabolites of several species of Aplysia and algae of the genus Laurencia involved enantioselective epoxidation as a key "*%. (668) X=Br (669) X = H The Antarctic nudibranch Tritoniella belli contains 1-0-eicoseriyl glycerol (670) 1 -0-2-methoxyhexadecyl glycerol (67 1) and the familiar compound chimyl alcohol (672) which deters feeding of the omnivorous sea star Odontaster validus and was also found in the co-occurring soft coral Clavularia frar~kliniana.~~~ The eicosanoid (673) which was isolated from Haminaea templad~i,~'~ was synthesized in five The HOJOR (670) R = CaH41 (673) (671) R = -CH2CH(OMe)Cl4H~ (672) R = C16H33 NATURAL PRODUCT REPORTS 1996-D.J. FAULKNER structures of (+)-(6R 1 1R)-9,10-dehydrofurodysinin (674) from Spanish specimens of Hypselodoris ~ebbi~~~ and ent-pallescensin-A (675) 15-acetoxy-ent-pallescensin-A(676) and 2,15-diacetoxy-ent-pallescensin-A (677) from Spanish Rl@ (674) R2 (675) R' = R2= H (676) R' = H; R2= OAC (677) R' = R2 = OAC specimens of Doriopsilla areolata were elucidated by spectral and chemical The transfer of secondary metabolites from the Mediterranean sponges Dysidea fragilis and Pleraplysilla spinifera to the mantle dermal formations (dorsal glands) of H.webbi has been The South African nudibranch Leminda melicra contained four sesquiterpenoids millecrones A (678) and B (679) and millecrols A (680) and B (681) which are probably of soft coral origin.456 Two metabolites of Acanthodoris nan~imoensis,~~'*(+)-iso-458 acanthodoral (682) and (-)-nanaimoal (683) have been 460 /CHO I (p/ %HO In addition to the known compounds photodeoxytridachione (684) and 9,lO-deoxytridachione (685),461*46z the Mediterranean ascoglossan Elysia timida contains two new polypropionates 15-norphotodeoxytridachione (686) and is0-9,lO-R+* 0 (684) R = Me (686) R=H * 0 0 deoxytridachione (687).463 The structure of siphonarienal(688) which is a polypropionate from the pulmonate mollusc Siphonaria grisea was determined by interpretation of spectral data and confirmed by enantioselective ~ynthesis."~ Two new polypropionates caloundrin B (689) and funiculatin A (690) were obtained from Siphonaria zelandica and S.funiculata 0 **. c.^." ,o.. respe~tively."~ The absolute configuration of the siphonarins from S. ~elandica~~~ were and baconipyrones from S. bac~ni~~~ determined by enantiocontrolled synthesis of a y-pyrone The absolute configuration of siphonarin A (69 1) OH was determined by X-ray analysis of a p-bromophenylboronate derivative.46g An interesting configurational model for siphonariid polypropionates has been derived from structural and biosynthetic consideration^.^^^ The absolute configuration of muamvatin (692) which is a metabolite of Siphonaria no~malis,~'~ was determined for a second time by synthesis of a degradation The structure of onchitriol I1 (693) from the pulmonate Onchidium sp.473 has been confirmed by synthesis but the same studies cast doubt on the structure assigned to onchitriol I.474 0 A New Caledonian pulmonate of the genus Onchidium has yielded onchidin (694) which is a cytotoxic depsipeptide with C Six new alkaloids monodontamides A-F (694) (695)-(700) have been isolated from the gastropod mollusc Monodonta labio from Japan the structures of the mono- dontamides which exhibit weak inhibition of a serine protease were determined by analysis of spectral data and unambiguous H N-N H 00 0 NHR3 (695) R' = R2 = H; R3 = CHO (696) R' =OH; R2=OMe; R3 = CHO (697) R'=OH; R2=OMe; R3=H (698) R=CHO (699) R = H H "4 nN 00 0 NHCHO The total syntheses of (f)-surugatoxin (701) and neosurugatoxin (702) have been 478 Na venones HOGOH NATURAL PRODUCT REPORTS,1996 A-C (703)-(705) which are alarm pheromones from Navanax iner~is,~~~ have been synthesized in a convenient manner.48o A neurotoxin isolated from the New Zealand shellfish Austrovenus stutchburyi has been identified as (4-methoxycarbonylbuty1)-trimethylammonium chloride (706).481 R (704) R=H (705)R=OH 10 Tunicates Tunicates (ascidians) are an increasingly popular target for study because of the frequency with which biologically active compounds are encountered.Four simple sulfates (707)-(7 lo) were identified as the antimicrobial constituents of Hulocynthia roret~i~~' from Japan and one of these sodium (or potassium) -0S03Na _.--Y-ToS03Na 2,6-dimethylheptyl sulfate (7lo) was found in Polycitor adriaticus from The structures of three 10-membered lactones didemnilactones A (711) and B (712) and neo- NATURAL PRODUCT REPORTS 1996-D. J. FAULKNER didemnilactone (71 3) which were obtained from a Japanese specimen of Didemnum moseleyi were elucidated by interpret- ation of spectral data and confirmed by synthesis the didemnilactones inhibit 5-and 15-lipoxygenases and bind weakly to leukotriene B receptors.4s4 Tasmanian collections of Clavelina cylindrica have yielded five additional alkaloids cylindricines C-G (714)-(718).Cylindricines F (717) and G (718) are the first thiocyanates from an as~idian.,~~ The cytotoxic constituent of C. lepadiformis was found to be lepadiformine (719) which has an unusual zwitterionic struc- t~re.~~~ n n (7 18) (714) R =OH (715) R =OMe (716) R = OAC (717) R =-SCN y!y-0-(719) Four additional cytotoxic cyclic polyethers bistramides B (720) C (721) D (722) and K (723) have been described without stereochemistry from Lissoclinum bistratum from both (720) R' = -COC,H,; R2 = H; R3 = -CH(OH)CH3 (721) R' = -COCH=CHCH3; R2 = H; R3 = -COCH3 (722) R' = -CH(OH)CH=CHCH3; R2= H; R3 = -CH(OH)CH3 (723) R' = -CH(OH)CH=CHCH,; R2= Me; R3 = -CH(OH)CH New Caledonia and Fiji.487 The structure of mollamide (724) which is a cytotoxic cyclic heptapeptide from Didemnum molle from the Great Barrier Reef has been determined by X-ray crystallography and chemical degradation.4s8 The complete spectral assignment of didemnin H (725) from Trididemnum cyanophorum has been reported.489 The structure of lisso- clinamide 5 from Lissoclinum pat ell^^^^^ 491 has been revised from (726) to (727) as the result of the total synthesis of both The structure of patellamide A (728) which is a cyclic peptide from L.patella,493was confirmed by an X-ray crystallographic Enantiomerically pure oxazole and thiazole amino acids were employed in a total synthesis of oc (725) 0 "Ph NATURAL PRODUCT REPORTS 1996 bistratamide C (729),495 which is a cyclic peptide from L.D (742) and lissoclins A (743) B (744) and C (745).502In a bi~tratum.~~~ paper describing the inhibition of topoisomerase I1 catalytic activity by pyridoacridine alkaloids three new representatives +NH HNAO Ho@s-s$ s-s OH (729) The unstable /I-hydroxy acid (730) was isolated from the Red Sea ascidian Didemnum granulat~rn.~~' The structure of lissoclinotoxin A from Lissoclinum perforat~rn~~* was revised \ NHR~ (743) R' = SMe; R2 = -COCH2CH(CH3)2 (744) R' = SMe; R2 = -CO(CH3)C=CHCH3 (€) ec"" (730) (748) R' = H; R2 = -COCH3 (750) R1 = SMe; R2 = -COCH3 from (731) to (732) and a new pentasulfide lissoclinotoxin B (733) was identified by interpretation of spectral data.499 N,N-dimethyl-5-(methylthio)varacin (734) and the corresponding trithiane (735) were obtained from L.japonicum from Palau. 3,4-Desmethylvaracin (736) was isolated from a Pohnpeian Eudistoma sp. and an inseparable mixture of 5-(methy1thio)- varacin (737) and the corresponding trithiane (738) was obtained from a Pohnpeian Lissoclinum SP.~OOTwo groups have reported that unsymmetrically substituted benzopentathiepins can exist as chiral m01ecules.~~~~ 502 Both varacin (739) which was isolated from L. ~areau,~O~ and isolissoclinotoxin A (740) ?R' OMe (731) R' = R2 = R3 = H (733) N~4~ (732) R' (734) R' (736) R' (737) R1 (739) R' (740) R' = Me; R2 = R3 = R4 = H = R2 = R4 = Me; R3 = SMe = R2 = R3 = R4 = H = R2 = Me; R3 = SMe; R4 = H = R2 = Me; R3 = R4 = H = R3 = R4 = H; R2 = Me have been synthesized.504 505 A specimen of Lissoclinum sp.from the Great Barrier Reef contained lissoclinotoxin A (732) and five new compounds lissoclinotoxin C (741) lissoclinotoxin HO&SMe YSMe (741) dehydrokuanoniamine B (746) shermilamine C (747) and cystodytin J (748) were described along with several known compounds from a Fijian Cystodytes sp.506 Cystodamine (749) is cytotoxic polyaromatic alkaloid from the Mediterranean ascidian Cystodytes delle chiujei that has a slightly different ring The total synthesis of diplamine (750) which is a cytotoxic alkaloid from Diplosoma SP.,~O~ was accomplished in 21 Meridine (751) which is an alkaloid from (746) (747) (749) R=NH2 (751) R=OH Amphicarpa meridiana,b10 was synthesized in four steps including a hetero Diels-Alder reaction.511 Three polyaromatic alkaloids polycitrone A (752) and polycitrins A (753) and B (754) were isolated from Polycitor sp.from South The structure of polycitrone A (752) was determined by X-ray crystallographic analysis of the corresponding penta-0-methyl derivative. NATURAL PRODUCT REPORTS 1996-D. J. FAULKNER HO *OH Br Q OH (752) Br Br (753)R = H (754)R=Me Eusynstyelamide (755) which is a cytotoxic dimeric peptide from Eusynstyela misakiensis from the Philippines possesses an unusual a-keto amide hydrate moiety.513 A West African Eudistoma sp.contained arcyriaflavin A (756) and stauro- sporine aglycone (757) which was responsible for the strong H (755) O+X Qp-$ HH (756)X=O (757)X=H2 cytotoxicity and protein kinase C activity of the crude extracts both compounds were previously found in The alkaloids eudistomin U (758) and isoeudistomin U (759) which is not actually an isomer were obtained from the Caribbean ascidian Lissoclinum fragile.515 Eudistomin T (760) which is a metabolite of Eudistoma olivace~m,~~~ has been synthesized in an efficient manner by two different route^.^^',^^' Rigidin (761) which is a phosphodiesterase inhibitor from Eudistoma cf. ~igida,~l~ was synthesized in a straightforward manner.52o Ph 0 OH Terpenoids are rarely found in ascidians.A second chlorinated diterpene chlorolissoclimide (762) has been iso- lated from Lissoclinum voeltzkowi and both (762) and dichlorolissoclimide (763) have been implicated in human food (762)R=H (763)R=CI poisoning resulting from the consumption of cooked oysters from whose shells the ascidians had not been removed.521 The structure of longithorone A (764) which is an interesting dimeric prenylated quinone from Aplidium (= Aplydium) longithorax was determined by X-ray analysis.522 Ritterazine A (765) is a highly cytotoxic dimeric steroidal alkaloid similar in structure to the cephal~statins,~~~ that was isolated from the 0 Q-$) H (758) (759) Japanese ascidian Ritterella t~kioka.~~~ Shimofuridin A (766) is a cytotoxic metabolite of mixed biosynthesis from an Okinawan specimen of Aplidium multiplicatum :525 shimofuridins B-G (767)-(772) are minor metabolites from the same 0 How HO 0 I RO 0 0 0 0 0 (767)R=\* /I \ 0 0 0 NATURAL PRODUCT REPORTS 1996 cytotoxic cerebrosides from the Mediterranean sea star Ophidiaster ophidiamus (= ophidian~s?).~~~ Cerebrosides CE-2b (781) CE-2c (782) and CE-2d (783) were isolated from the sea cucumber Cucumaria echin~ta~~~ and cerebrosides PA-0-1 (784) PA-0-5 (785) PA-2-5 (786) and PA-2-6 (787) were found in Pentacta au~tralis.~~~ The structures of the cerebrosides were elucidated on the basis of chemical and spectroscopic methods.CHzOH i OH (768)R =\--\ -0 0 0 0 0 0 0 The inhibitors of protein tyrosine kinase pp60"-"'" from the brittle star Ophiarachna incrassata were shown to be five sterol sulfates only one of which (788) was a novel 0 Five new sterol sulfates (789)-(793) were found in the brittle 11 Echinoderms The isolation of 2-hydroxycarboxylic acids (773)-(775) from Tripneustes esculentus is a rare report of natural products from a sea Ophidiacerebrosides A-E (776)-(780) are OH HOOC (773)n= 1 (774)n= 2 (775)n= 3 0 OS03Na bH (776)R = (778)R = (779)R = (780)R = (777)R = CmH41 ClgH3gC21H43 C22H45 C1&7 Na03S000v OH (789) NATURAL PRODUCT REPORTS 1996D. J. FAULKNER OS03Na I (790) R’ = H; R’ = OH (791) R’=OH; R2=H ?S03Na YH HO (792) 24R (793) 24s star Ophiopholis aculeata collected at a depth of 200 m in the Okhotsk Sea but only known compounds were obtained from Ophiura sarsi and Stegophiura brachiacti~.~~~ The deep-water (2000 m) starfish Styracaster caroli contained ten poly-hydroxylated sterols eight of which (794E(801) were new.533 The structures of the sterols were elucidated by interpretation of spectral data.(794) R = *=-OH OH -(795) R = -=&OH .Mn (798) R = “*~OSO3Na OH .MN OH (0S03Na (800) R= .MN Na03S0 HO VOH Cosmasterosides A (802) B (803) C (804) and D (805) are new sulfated asterosaponins from the Atlantic starfish Cosmasterias lurid^^^* that were isolated together with the known metabolites ophidianoside F (806) from Ophidiaster 117 OH HO (803) R’ = OH; R’ = Fucose (asin 802) (804) R’ = R2= H (805) R‘ =OH; R’ = H (806) R‘=H; R2=Fucose ophidian~s~~~ and forbeside H (807) from Asterias forbe~i.~~~ Solasterosides S (808) and S (809) were obtained from the starfish Solaster dawsoni from the Sea of Okh~tsk.~~’ The sea OH cucumber Eupentacta fraudatrix contained a new penta-nortriterpene glycoside cucumarioside G (810) as a minor metabolite.538 Among the polar metabolites of the sea cucumber Cucumaria frondosa were 1-0-[( 113-octadecenyll-sn-glyceryl-3-phosphorylcholine (8 11) and 1,3,9-trimethyl-8-nitroso-isoxanthine (812).539 Do not be misled by the report that dimers and trimers of styrene were isolated from the starfish 118 NATURAL PRODUCT REPORTS 1996 " O ~ o OH ~ o HO HO 0 H I (H"T 0.OH (810) 0-(81 1) Pteraster militaris these compounds were undoubtedly leached from Amberlite XAD-2 resin.54o 12 Miscellaneous The structures of cephalostatins 10 (813) 11 (814) 14 (815) and 15 (8 16) which were isolated from the tube worm Cephalodiscus gilchristi collected off southeast Africa were elucidated by . -2--2 OH AJ. ' (813) R' = OMe; R2 = H 'OH (814) R' = H; R2 = OMe comparison of spectral data with those of previous compounds in this series.541* 542 The luminescent marine polychaete worm Odontosyllis undecimdonta contains two additional bases (5')-6-(1-hydroxypropyl)-3-methyllumazine (8 17) and (S)-6-(1-hydroxypropyl)-l,3-dimethyllumazine(81 8).543 The synthesis of (+)-bromoxone (819) which is a metabolite of the acorn worm Ptychodera sp.,544 has been synthesized in a stereoselective manner.545 R (817) R=H (818) R=Me The structure of the hatching of the barnacles Balanus balanoides and Eliminus modestus has been confirmed by synthesis to be (52,8R,9E,ll Z,142,17Z)-8-hydroxyeicosa-5,9,11,14,17-pentaenoic acid (820).547 Squalamine (821) which is an antibiotic from the dogfish shark Squalus acanthiu~,~*~ was synthesized from 3P-acetoxy-5-cholenic acid."' 13 References 1 D.J. Faulkner Nut. Prod. Rep. 1984 1 251. 2 D. J. Faulkner Nut. Prod. Rep. 1984 1 551. 3 D. J. Faulkner Nat. Prod. 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ISSN:0265-0568    

DOI:10.1039/NP9961300075

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

B-Phenylethylamines and the lsoquinol ine Alkaloids K. W. Bentley Marrview Tillybirloch Midmar Aberdeenshire AB5 1 7PS UK Reviewing the literature published between July 1994 and June 1995 (Continuing the coverage of literature in Natural Product Reports 1994 Vol. 12 p. 41 9) 1 P-Phenylethylamines 2 Simple Isoquinolines 3 Naphthy lisoquinolines 4 Benzylisoquinolines 5 Bis benzylisoquinolines 6 Cularines 7 Pavines and Isopavines 8 Berberines and Tetrahydroberberines 9 Secoberberines 10 Protopines 11 Pht halide-isoquinolines 12 Spirobenzylisoquinolines 13 Rhoeadines 14 0ther Modified Berberines 15 Emetine and Related Alkaloids 16 Benzophenanthridines 17 Aporphinoid Alkaloids 17.1 Proaporphines 17.2 Aporphines 17.3 Aporphine-Benzylisoquinoline Dimers 17.4 Dimeric Aporphines 17.5 Phenanthenes 17.6 Oxoaporphines 17.7 Dioxoaporphines 17.8 Aristolochic Acids and Aristolactams 17.9 Oxoisoaporphines 17.10 Azafluoranthenes and Related Alkaloids 18 Alkaloids of the Morphine Group 19 Phenethylisoquinolines 20 Colchicine and Related Alkaloids 21 Erphrina and Related Alkaloids 21.1 Erjtthrina Alkaloids 21.2 Cephalotaxine and Related Alkaloids 22 Other Isoquinoline Alkaloids 23 References 1 p-PhenyIethyIamines N-trans-Feruloyltyramine(I) has been isolated from Dactylo- carpus torulusa.' The resolution of racemic ephedrine has been achieved by liquid chromatography using 1-(9-fluorenyl)ethyl chloroformate as an on-line pre-column chiral derivatizing agent.' Phosphorylation of (-)-ephedrine with O-dialkyl-dithiophosphates has afforded a series of esters of structure (2) which are shown to have pharmacological properties similar to those of ephedrine but with appreciably lower acute toxi~ity.~ An X-ray crystallographic determination of the structure of (-)-ephedrine thiocyanate has been rep~rted.~ Methods for the detection and estimation of ephedrine5 and of pseudoephedrine6 in body fluids have been reported and studies have been made of the use of ephedrine in Mescaline has been used as the starting material for syntheses of tetrahydroberberines (see Section 8).2 Simple lsoquinolines ( +)-Salsolidine has been isolated from Arthrocnemum glau~um,~ the new tetrahydroisoquinoline alkaloid north-alifoline (3) has been isolated from Lindera megaphylla," and the novel and unusual alkaloid excentricine (4) has been obtained from Stephania excentrica." The structure of excen- tricine was deduced entirely from its spectra but that of northalifoline was confirmed by conventional synthetic met hods.Good enantionmeric separation of (+)-and (-)-isosalsoline (5) has been accomplished by high performance liquid chromatography (HPLC) using /?-cyclodextrin-bonded silica as the stationary phase with a variety of different solvents.12 A synthesis of arizonine (8) has been achieved from the phenol (6) by Fries rearrangement of the 0-acetyl ester to the keto-nitrile (7) followed by reductive cy~1ization.l~ (-)-(S)-Carnegine (I1) has been synthesized by desulfurization of the sulfoxide (1 0),prepared by cyclization of the olefin (9) according to previously reported 1lleth0ds.I~ (9) M MeOe o q N Me 127 NATURAL PRODUCT REPORTS 1996 (19) from which the rotamers michellamine B (20) and 3 Na phthyl isoquino1ines michellamine C (2 1) were prepared by thermal equilibration.l* The new alkaloids korupensamine A (12a) korupensamine B Michellamines A and B have been isolated from Ancistrocludus (13) korupensamine C (12b) and korupensamine D (14) have korupensis but michellamine C has not so far been identified in been isolated from Ancistrocladus korupensis,15 and 5'-O-natural material.lg A similar preparation of the michellamines demethyl-8-O-methyl-7-epi-dioncophylline A (15) also a new has been achieved from the chiral tetrahydroisoquinoline (23) alkaloid together with its previously known rotamer has been prepared in optically pure form from the chiral 1-isolated from Triphyophyllum peltatum.16 The structures of the phenylethylimine (22) by a previously reported route.korupensamines were deduced from detailed studies of their Demethylation of (23) followed by N,O-benzylation and NMR spectra and that of korupensamine A was confirmed by an X-ray crystallographic examination of its p-bromo-Me OH benzenesulfonyl ester.'j In addition a mixture of the rotamers #I korupensamines A and B has been synthesized by the reductive coupling of the naphthalene (1 6) and the tetrahydroisoquinoline (17) in the presence of a palladium(r1) catalyst." Me OH Me-OR OMe OH OMe OMe OH \ 0 Me Me Me "WHMe 6~ tie OH Me (19) (12a)R= H (13) (12b)R=Me OH OMe Me OH c)$ Mew HowN Me0 OMe OH \ 0 Me OH Me HO (14) "OWHMe OH OMe OH Me (20) Me HNkJ& N-Formyl-O,O-diacetylkorupensamine A on oxidation with silver oxide in a mixture of triethylamine and chloroform has been converted into the dimerized quinone (ISa) and this on OH reduction with sodium borohydride and hydrolytic removal of the N-formyl and O-acetyl groups afforded michellamine A Me% OMe OH \ / Me OR2 (21) Me% OMe 0 \ 0 Me R20yJ-J:e Meoy-qyeH MeowHMe I I' OR^ he (18a)R' = CHO; R~ = AC OMe PhyMe OMe Me (lab)R' = R2 = CH2Ph (22) (23) NATURAL PRODUCT REPORTS 1996K.W. BENTLEY regiospecific iodination with iodine and silver carbonate gave (24a) which was condensed with the naphthylboronic acid (25) to give O-methoxymethyl- O,O,N-tribenzylkorupensamines A and B. Hydrolysis of the methoxymethoxy group and oxidation of the resulting O,O,N-tribenzylkorupensaminesA and B with silver oxide yielded the quinone (18b) reduction of which was accompanied by debenzylation to give a mixture of michell- amines A. B and C.20 Me -0 Me Ph (24a) R= I (24b) R = B(OH) (24c) R = Br An alternative synthesis of michellamines A and B has been accomplished by the construction of the central 2,2'-binaphthyl system and adding the two tetrahydroisoquinoline units.The bromo- 1,4-naphthoquinone (26) on treatment with copper bronze and tetra(triphenylphosphinyl)paIladium followed by reduction with zinc and acetic acid gave the binaphthyl (27a) which was selectively cleaved by diazabicycloundecane to the phenol (27b). Coupling of the di(trifluor0acetate) of this phenol with the boronic acid (24b) [prepared from (24)] with tetra(triphenylphosphiny1)palladium and barium hydroxide then gave O,O,N-tribenzylmichellamines A and B from which the alkaloids were prepared by hydrogenolysis. Michellamine C was not detected in the product of this synthesis.21 Both of these syntheses can be adapted to the preparation of analogues of these alkaloids with different substituents which could be of importance in view of the biological activities of the alkaloids against H IV.?R Me 0 OR (26) (27a)R=Ac (27b) R= H The rotational chirality of michellamines A B and C given in structure (19) (20) and (21) is based on detailed spectroscopic and circular dichroism studies,22 as well as on their relationship to korupensamine A. All three michellamines have been shown to be active against human immunosuppressant viruses (HIV) I and I1 in vitro.15,19. 23 Korupensamine A is inactive against HIV I and HIV 11 but shows activity against Plasmodium falciparum malaria.l5 4 BenzyIisoqu inoIines 1-Benzylisoquinoline alkaloids have been isolated from the following plant species that marked by an asterisk being a new alkaloid Lindera meguphyllalo reticuline Litsea ucuminatd4 juziphine norjuziphine N-methylcoclaurine and reticuline Ocoteu teleiandra25 5,6-demethoxytakatonine*(28) 129 Stephania aculeata26 laudanidine Stephania bancroftii26 laudanidine Stephania macranthaZ7 laudanidine and the novel 2-benzylisoquinoline alkaloids isosendaverine (29) capnosine (30a) and capnosinine (30b) have been isolated from Ceratocupnos heterocarpa.28 Me0 OMe "'OmN, RO QOH OMe (30a)R =H (30b) R=Me The original report of the isolation of (28) is not readily available but if the structure of this alkaloid is correct it is unique in being the only benzylisoquinoline alkaloid with no substituent at either C-6 or C-8.Indeed of the alkaloids derived from tyrosine only one an aporphine has been assigned a structure with only one oxygen substituent in the isoquinoline portion of the molecule (and that at C-6) so structure (28) should be regarded with some suspicion.The isolation of laudanidine from Stephania species represents the first recorded incidence of this alkaloid in the Menispermaceae. (S)-(-)-Noranicanine (32) has been synthesized in high enantiomeric yield from the chiral formamidine (31) by deprotonation with butyllithium treatment of the anion with 3-benzyloxybenzyl bromide and hydrogenolytic cleavage of the Racemic laudanosine has been synthesized by treating the dihydroisoquinolinium salt (33) with the lithium salt (34) of the cyclic thio-acetal of veratric aldehyde followed MeO ';1 Me0 MeomN I Pr' y-Me BdOd H' boH ,-s Li+ (33) (34) by desulfurization of the product (35).30 Good enantiomeric separation of racemic laudanosine has been achieved by HPLC using P-cyclodextrin-bonded silica as the stationary phase and a variety of organic solvents ;increased efficiency was achieved when P-cyclodextrin was added as a chiral selector to the mobile phase.12 Me0 M e O K OMe ' me (35) Papaveraldine and the isoquinoline (36) have been obtained NATURAL PRODUCT REPORTS 1996 A patent has been published covering the preparation of 0-demethylrodiasine (40) and its derivatives and their use as antitumour agents febrifuges virucides contraceptives and pesticide^.^^ OMe k+yL& OH HO The pharmacological properties and physiological effects of berbamine,50.51 of ~epharanthine,~~-~~ of of o~yacanthine,~~ tetrand~ine~~-~~ and of tubocurarine7@'* have been studied.by the oxidation of papaverine with (diacetoxyi~do)benzene,~l and oxidation of the alkaloid with 4-acetoxy-2,2,6,6-6 Cularines tetramethyl-1-0xopiperidine perchlorate has yielded the The highest yielding syntheses of racemic cularine and sarcocapnidine so far recorded have been achieved by the bimolecular salt (37). 32 ~~~~$~~~ cyclization of nitrenium and oxonium ions generated as short- MeOq (30,-lived intermediates. Reduction of the 3'-nitro benzyldi hydro- \ 'N Me0 ,N' ,OMe Me0 / ' 'OMe OH Me0 (36) (37) The pharmacological properties and physiological effects of pa~averine~~-~~etha~erine,~~ laudano~ine,~~ of of of higenamine,33,40 41 and of atracurium 42-44 have been studied.5 Bisbenzylisoqui no1 ines Bisbenzylisoquinoline alkaloids have been isolated from the following plant species the two marked with asterisks being new alkaloids Cocculus tri10bus~~ 1,2-dehydroapateline and neotrilobine* (38) Epinetrum villos~m~~ coscoline cosculine cosculine N-oxide" (39) cycleanine cycleanine N-oxide and norcycleanine Menispermum dau~icum~~ dauricine and daurisoline Stephania ~epharantha~~ aromoline berbamine cepharanoline cepharanthine cycleanine norcycleanine homoaromoline isotetran- drine and obamegine. Neotrilobine (38) is a new secobisbenzylisoquinoline alkaloid representing a stage of degradation not previously encountered in the group the retained benzyl group bearing no residue of the normal benzyl-benzyl linkage.isoquinoline (41a) gave the amine (41b) which was converted by conventional processes into the azide (41c). Treatment of this with trifluoromethanesulfonic acid in carbon tetrachloride at low temperature generated the nitrenium ion and at the same time liberated the phenol from its benzyl ether with consequent cyclization to the same (42a); this was converted through the diazonium salt (42b) and the phenol (42c) into dehydro- norcularine (42d) and the N-methyl salt of this gave cularine (43a) on reduction with sodium b~rohydride.~~ In an alternative approach the phenol (44a) was converted into the anion by treatment with sodium hydride under anhydrous conditions and the anion on oxidation with (diacetoxyiodo)benzene afforded the oxenium ion which cyclized to (42d).Dehydro- cularine (42d) was obtained by both of these routes in yields around 87 Oh based on the original benzylisoquinolines (44a) and (41a). Racemic cularine obtained in these ways was resolved into its (+) and (-) forms by conversion into the separable quaternary salts with (+)-8-phenylmenthyl chloride followed by reductive cleavage to the tertiary bases. Repetition of the approach through the oxenium ion using the benzyl ether (44b) with final debenzylation gave a mixture of the racemates of the isomeric alkaloids enneaphylline (43b) and sarco-capnidine (45).73 Me0 M e O V Ph-0-Q Q Me0 R Me0 R (41a) R=NOp (41b)R = NH2 (41~)R=N3 (Ma)R = NH2 (42b)R=N2+ (42~)R=OH (42d)R=OMe --MeO??Me Me0\I OR Me0\/OR -% Meo2Me Ho \ / OH (43a)R=Me (44a)R=Me Me0 (39) (43b)R=H (a) R=CH2Ph (45) NATURAL PRODUCT REPORTS 1996-K.W. BENTLEY In a variant of a previously reported sequence clavizepine (52) has been synthesized from the diphenyl ether (46) by cyclization to the hydroxy-ester (47) followed by hydro- genolysis to the ester (48a). This was converted through the N-methyl amide into the amine (49) which was acylated with S-methylthioglycollic acid to the amide (50) the sulfoxide of which yielded the lactam (5 1) on cyclization with trifluoroacetic anhydride. Reductive desulfurization of this lactam yielded clavizepine (52).74 The ester (48b) which was also converted into clavisepine has been prepared by the cyclization of the anion (53).75 Ph Ph OMe OMe (46) (47) Ph Ph OMe (Ma) R=OEt 6Me (48b) R=OMe (49) Ph Ph OMe OMe (50) (51) HOJF& Me Ph OMe OMe OMe OMe (53) (52) Fries rearrangement of the appropriate ester of the phenol (6)to the ketone (54) followed by reduction and cyclization has afforded the cularine precursor norcrassifoline (55).13 The pharmacological properties of sauvagnine have been Me0 M eHO 0-2H OH \/ OMe Me0 OH 7 Pavines and lsopavines Three new isopavine-benzylisoquinoline dimers namely herveline A (56a) herveline B (56b) and herveline C (56c) have been isolated from Hernadia voyronii.Their structures were determined from their spectra particularly by their mass spectral fragmentation to the ions (57a) (57b) and (58). These alkaloids were isolated during an evaluation of the plant material as a potential antimalarial.77 OR2 (%a) f?‘ = H; R2= Me (%b) R’ = Me; R2= ti (56c) R’ = R2 = Me OMe i57bj R2 = Me 8 Berberines and Tetrahydroberberines Alkaloids related to berberine have been isolated from the following plant species the two marked with asterisks being new alkaloids Chelidonum major78 coptisine Copt is ch inensis7 berberine Cop tis deltoide~~~ berberine Copt is gulinensis7 berberine Copt is omeiensis berberine Dactylocarpus torulosal isoapocavidine* (59) cheilanthifoline dimethylcory- daldine 1-methoxyberberine and stepholidine Fissistigma glaucescenssO discretamine Guatteria foliosagl coreximine Menispermum da~ricum~~ dauricoside* (60) Me0 Papaver pinnatiJidurna2 berberine and scoulerine Stephania aculeataZ6 tetrahydropalmatine Stephania bancroftiis3 tetrahydropalmatine Stephania ma~rantha~~ corydalmine palmatine tetrahydropalmatine and stepholidine.A review of the production of alkaloids of this group in Nandina dornestica has been published.a4 Berberine and palmatine have been shown to be converted into their tetrahydro derivatives and tetrahydroberberine has been shown to be converted into N-methyltetrahydroberberinium chloride and the protopine alkaloid muramine in cell cultures of Corydalis ~allida.~~ An enzyme that catalyses the formation of the methylenedioxy group of (S)-canadine (61) from (S)-tetrahydrocolumbamine has been isolated from Thalictrum tuberosurn.a6 The keto-aziridine (63) has been prepared by the photolysis of berberine betaine (62) in the absence of oxygen and has been hydrolysed by aqueous acid to the spiro-compound (64).87,88 A review has been published covering the laboratory conversions of alkaloids of the berberine group into those of the benzop henanthridine group 0 9 -OYXoMe OMe (62) -\ / OMe OMe Methods of estimating berberinegO and tetrahydropalmatine” in plasma have been described.In syntheses within the group mescaline (65) has been condensed with the isomeric isochromoman-3-ones (66a) and (66b) to give the lactams (67a) and (67b) and cyclization of these by the Bischler-Napieralsky process with phosphorus oxychloride followed by reduction with sodium borohydride yielded racemic 0-methylcapauridine (68a) and 0,O-dimethyl- stephabinamine (68b) respectively.92 Radical-induced cyclizations of the enamides (69a) and (69b) by processes previously reported has given 8-oxopalmatine (70a) and 8-oxoberberine (70b) ; reduction of these gave 8-oxotetra-hydropalmatine (71a) and gusanlung B (71 b).93 NATURAL PRODUCT REPORTS 1996 Me0FNH2 Me0 OMe 0 OMe (66a) R’ = H; R2 = OMe (67a) R’ = H; R2 = OMe (66b) R’ = OMe; R2= H (67b) R’ = OMe; R2 = H (68a) R‘ = H;R2 = OMe (69a) R‘ = R2 = Me (68b) R’ = OMe; R2 = H (69b) R1R2= CH2 R’0 R20WNvO boMe OMe (70a) R’ = R2 = Me (7la) R‘ = R2 = Me (7%) R1R2= CH2 (7lb) R’R2= CH2 The pharmacological properties and physiological effects of be~berine~~-~~ 99 berberr~bine,’~ tetrahyd~berberine,~~.~oralyne,’~ discretamine,ao tetrahydropalmatine,loo dehydro- xylopinine (72a) and its isomer (72b),I0* 3,9-0,O-demethyl- stepharanine,” and of 3 10-0,0-demethylcoreximine102 have been studied. MeO R’ R2 OMe (72a) R’=H; R2=OMe (72b) R’=OMe; R2=H 9 Secoberberines Secoberberine alkaloids have been isolated from the following plant species the three marked with asterisks being new alkaloids Hypecoum procumbenslo3 hypecorinine and 8-oxohypecorinine* (73) wo OJ (73) NATURAL PRODUCT REPORTS 1996-K.W. BENTLEY Dactylocarpus torulosa' torulosine* (74a) and torulosinine* (74b). The structures assigned to the isomeric alkaloids egenine (75) and humosine A (76) and to humosine (77) have been supported by spectroscopic studie~.'~~~ lo5 R'O R20%i /+ OH OMe (744 R1R2= CH2 (74b) R' = R2 = Me to give (84a) which is readily converted into the alkaloid hypecumine (84b),lo7 <%o) '0 (84a) R=C02Et (84b)R=Me 10 Protopines Alkaloids of the protopine group have been isolated from the following plant species Dactylocapnos torulosal hunnemanine and protopine Hypecoum procumben~'~~ allocryptopine cryptopine and protopine 0 0 (OXO)Papa ver p inn a t@dum8 ,'o Hd (76) The anions of benzocyclobutenols have been found to react with aromatic aldehydes under anhydrous conditions with ring opening and cycloaddition to give cyclic hemiacetals which are easily oxidized to 3,4-dihydroisocoumarins and in this way peshawarine (83) has been synthesized from hydrastinine (78) by treatment with ethyl chloroformate to give the aldehyde (79) and condensation of this with the anion (81) generated from the benzocyclobutenol (80) and butyl lithium.Methanolysis of the resulting anion gave the mixed acetal(82) from which peshawarine (83) was prepared by reduction of NC0,Et to NMe and oxidation to the lactone.lo6 A similar cycloaddition takes place between the anion (8 1) and nitriles with the loss of methanol to give pyridines and the nitrile obtained by the dehydration of the oxime of (79) adds to (81) J 0' allocryptopine and protopine.Tetrahydroberberine has been found to be converted into muramine in cell cultures of Corydalis pallid^.^^ The effects of protopine on platelet functionslo8 and on experimentally induced cardiac arrhythmiaslog have been studied. 11 Phthalide-isoquinolines The following alkaloids of the phthalide-isoquinoline group those marked with asterisks being new alkaloids have been isolated from Dactylocapnos torulosa adlumidine bicuculline fumaridine a-hydrastine P-hydrastine N-methylhydrasteine chloride* (86) N-methylhydrasteine methyl ester chloride* (86b) N-methylhydrasteine hydroxylactam chloride* (87) (N-methylfumschleischerine chloride) and oxocoryrutine* (85).l OMe ct-<xly& ' OMe OMe (86a) R = H (86b)R=Me cr 0 HN0%OMe OMe 134 with formaldehyde hydroisoquinoline ray crystallographic study.ll" R (88a) R = H (88b) R= Br <% Me0 Et0& reduced to a and threo forms of cordrastine (93a).'12 bicuculline have been studied.'13.114 R2OA -0 "A (92a) R' (92b) R' R2 Ho* NATURAL PRODUCT REPORTS 1996 gler and acid (89) but cyclizatios blocked as tion led to thdium borohydwas further reduced catalytic(91b) the detailed structure Pictet-Spencyclization waMannich reacwhich with so has when n of nornin the bre benzazride gave ally to the of which given the aromepthraw Me ceio­ine e lceas c the novel tetra-position for this compound (88b) mic threo compound ne ethyl ester (88a) (90) reduction of actone (91a) which onfirmed by an X-I2 Spirobenzyl isoqui no1ines Photolysis of berberine betaine (62) in the absence of oxygen has given the aziridine (63) which has been hydrolysed in acid to the spiro-compound (64),*'~*~ with an arrangement of substituents not found naturally.Deprotonation of the tetrahydroisoquinolines (96a) and (96b) at C-1 in the presence of an excess of base ensuring a second deprotonation of the initial product and treatment with either of the isomeric lactone-acetals (97) and (98) has yielded the racemic alkaloids corydaine (99a) and yenhusomidine (99b) and reduction of yenhusomidine prepared in this way has afforded raddeanine ( a " ' " ~ N TBF3-Me R20 OMe OMe (89) (%a) R' R2 = CH2 (96b) R' = R2 = Me (97) (98) Me0 (90) Alkoxy-substitut OMe ed benzyl alcohols hav (91(91b) R=H e b OMe Me0 a) R = Br phthalides een converted into R'O mixh reaand in this way littetrinto cordrastine (93parallel process the bromohydroxylauddianions whicand P-hydroxy tct with chium saltahydoescholamine(9a) and bicuculline (93dihydroisoquinoliniuure of erythro and anosine (95) into which s of P-hydroxy2b) have been b) m thrcarbon arbon dio xi de to give laudanosine (92a) respectively.lll In a salt (94) has been eo isomers of 6'- (99a) R'R2 = CH (99b) R' = R' = Me converted monoxide ted bhas been inserpalladium catalyst in trimeth y treatm ent with ylsilyl chl caroride bo giving the n monoxide and a 13 Rhoeadineserythro cologThe pharma ical prop erties and p hys iological effects of Papaverrubines A C and D have been isolated from Papaver pinnatifidum.82 14 Other Modified Berberines = R2 = = Me CH2 (93a) R' ( 93 b) OR2 = R2 = Me = CH2R' R2 The tetrahydroisoquinoline (101a) has been converted through (101 b) into the base (102) the N-oxide of which when subjected to a Polonovski rearrangement gave the isoxazolidine (103).Reduction of this gave the alcoholic amine (104) and the related N-(6-bromo-2,3-dimethoxybenzoyl)compound on oxidation was converted into the ketone (105a) and then into the a-phenylthio-ketone (105b); elimination of thiophenol from this gave the a$-unsaturated ketone (106) which was cyclized by irradiation to magallanesine (107).'16 15 Emetine and Related Alkaloids (94) OMe 6Me M eMe0 o w Ho?x$ N M e OMe OMe (95) The three new alkaloids isoalangiside (108a) methyl-isoalangiside (108b) and 3-O-demethyl-2-O-methyliso-alangiside (1 08c) have been isolated from Alangium 1amarckii.l" Isoalangiside is epimeric at C-1 of the isoquinoline system with alangiside which has been isolated from the same plant.These alkaloids are clearly derived from deacetylisoipecoside (1 09) which is the known precursor of protoemetiene (110) and the alkaloids derived from it such as emetine and alangimarckine. NATURAL PRODUCT REPORTS 199CK. W. BENTLEY (101a) R=OH (101b) R =CI (108a) R' = Me R2 = H (108b) R' = R2= Me (108c) R' = H; R2 = Me Me0 CHO 16 Benzophenanthridines Alkaloids of the benzophenanthridine group have been isolated from the following plant species that marked with an asterisk being a new alkaloid Chelidonum major78 chelidonine Dactylocarpus torulosal 8-acetonyldihydrosanguinarine,norsanguinarine and 8- oxosanguinarine Fagara pterotalla norchelery thrine Fagara rhoifolia118 norchelerythrine Xan thoxylum ailanthoidesl l9 ailanthoidine* (1 1 1).(105a) R=H (10%) R=SPh Fagaronine has been isolated from cell cultures of Fagara zanthoxyloides.120The structure of ailanthoidine was suggested by its spectra and was confirmed by an X-ray crystallographic It presumably arises from chelerythine in the same way as the other 8-substituted alkaloids of the group by a Mannich reaction with a reactive methylene compound though the origin of 2-ethyl-4-cyanopyridine that would appear to be required in this case is obscure.Cyclization of the nitrile (112) with aqueous hydrofluoric acid (Hoesch reaction) has given the ketone (113) which underwent the Reformatsky reaction with zinc/ethyl bromo- acetate to give the P-hydroxy-ester (114). This was cyclo-dehydrated and oxidized by 75 YOsulfuric acid to the phenolic iminium salt (1 15) and the phenyltetrazolyl ether of this (1 16) was catalytically reduced and N-methylated to O-ethyl-fagaronine (1 17a) from which the ethyl group was removed by concentrated sulfuric acid to give fagaronine (1 17b) in 14 YO overall yield from (1 12).121 OEt Me0 Me0 OEt Me0 OMe Me0 Me0 (115) Me0 OMe MeO (117a) R=Me (117b) R=H 136 Condensation of the keto-ester (118) with beuylamine followed by treatment of the products with acetyl chloride afforded a mixture of the simple enamide (1 19) and the cyclized product (120); and both of these gave (121) on cyclization with phosphorus oxychloride.122 Me03 Me OMe OMe Me Ph Me0 OMe Me0 OMe Me0 Me Ph Me bh (120) (121) A review of laboratory conversions of alkaloids of the berberine group into benzophenanthridines has been published.89 17 Aporphinoid Alkaloids 17.1 Proaporphines Stephanine has been isolated from Anona ~acans,~~~ Stephania bancroftiis3 and Stephania ~epharantha.~~ A review of methods of synthesis of proaporphines has been p~b1ished.l~~ 17.2 Aporphines Aporphine alkaloids have been isolated from the following plant species the six marked with asterisks being new alkaloids Annona ~acansl~~ assimilobine and michelalbine Aristolochia brevipe~l~~ N-formylnornantenine and N-formyldehydronornan-tenine* (122) Guatteria foliosus' elmerillicine isoguattouregidine 3-hydroxynuciferine 3-methoxyguattescidine* (123) 3-methoxyputerine" (124) norguattevaline* (125) and norstephalgine OMe Me0 FCHO<F OH \ ' Me Me0 / / 0 L-0 OH NATURAL PRODUCT REPORTS 1996 Hypecoum procumbenslo3 isocorydine Lindera megaphyllalO dicentrine N-methylhernovine N-methylnandigerine and 0-methylbulbocapnine Lindera myrrha126 oduocine* (126) Litsea ac~rninata~~ actinodaphnine boldine isoboldine norisoboldine norisocorydine laurolitsine laurotetanine and lind-carpine Ocotea holdrigeianu127 isocorydine 0,O-dimethylcorytuberine 3-hydroxynuci-ferine and 3-methoxynuciferine Ocotea teleiandra25 hernovine laetamine laetine nandigerine and ovigerine Papaver pinnati$dums2 corytuberine isoboldine and isocorydine Papaver spicatum 28 N-methylglaucine chloride and N-methylroemerine chloride Piptostigma fugaxl 29 nornuciferine and N-formylnornuciferidine Stephania abys~inical~~ corydine crebanine dicentrine N-methyllaurotetanine roemerine stephalgine and stephanine Stephania bancroftii 83 ayuthiamine crebanine sebiferine and stephanine Stephania rnacrantha2? corydine isocorydine and corytuberine Stephania venosal kamaline* (127).The structures of the new alkaloids were determined principally by spectroscopic methods and kamaline was hydrolysed to assimilobine and D-glucose.Methylation of boldine (128a) with a restricted amount of diazomethane has afforded N-methyllaurotetanine (128b) and predicentrine (128c) both of which were further methylated by an excess of the reagent to glaucine (128d).132The solvolysis of boldine with aqueous ammonium acetate has given a high yield of the phenanthrene secoboldine (129).133 OH Meo9H Me0 -H (128a)R' = R2= H (128b)R' =Me; R2= H OH (128c)R1= H; R2=Me (125) (128d)R' = R2 = Me NATURAL PRODUCT REPORTS 1996-K. W. BENTLEY Deprotonation of the tetrahydroisoquinolinium salt (96b) with butyllithium and condensation of the resulting C-1 anion with o-bromobenzaldehyde afforded (130) from which racemic nuciferidine (13 1) was obtained by photolysis and removal of the b0r0n.l~~ Condensation of the enamide (132) with 3,5- dimethoxybenzyne generated in situ has given the 7-methyl- dehydroaporphine t 133) which was oxidized by molecular oxygen in aqueous alkali with concomitant hydrolysis to give racemic guaicoline (134).135 Me0 BF3 0 Me0 Me I I OMe OMe (133) (1 34) Among aporphines that do not occur naturally 3-methoxyapomorphine (1 35) has been prepared by the rearrangement of thebaine in methanesulfonic acid in the presence of ~ethi0nine.l~~ 10-Deoxyapomorphine (1 36),13' N- propyl-1O-deoxynorapomorphine (136b),13* 1O-methyl- 10- deoxyapomorphine (136~)'~' and 10-0-methylapomorphine (1 36d)13' have been prepared from apomorphine (1 36e).(136a) R' = H; R2 = Me (136b) R' = H; R2 = Pr (136c) R' = R2 = Me (136d) R' = OMe; R2=Me (136e) R' = OH; R2= Me A review of the chemistry of aporphines has been pub1i~hed.I~~ The pharmacological properties and the physiological effects of apom~rphine,l~~-'~~ of di~entrine,~~~, of b~ldine,l~~ 154 of g1aucinels5of thalip~rphinel~~ and of (S)-(+ )-aporphines in have been studied and a method of estimating apomorphine in body fluids has been described.158 17.3 Aporphine-Benzylisoaquinoline Dimers Thalifaracine thalifaramine thalifarazine thalifaronine and the new alkaloid thalifaberidine (1 37) have been isolated from Thalictrum faberi.Thalifaberidine has been shown to have antimalarial activity and to be cytotoxic to several human cancer cell lines. Its structure was determined from its NMR Meo@NMe "H Me0 ''H Me0 HoqNMe Me0 17.4 Dimeric Aporphines The 7,7'-dimeric aporphines urabaine N-methylurabaine N,N- dimethylurabaine trivalvone heteropsine and the new alkaloid N-methylheteropsine (138) have been isolated from Piptostigma f~gax.'~~ 17.5 Phenanthrenes Argentinine has been isolated from Guatteria foliosa.*l Secoboldine (129) has been prepared by the solvolysis of boldine (128a) with aqueous ammonium A patent covering the preparation of seco-aporphines and their use as antiarrhythmic agents has been published.160 17.6 Oxoaporphines Oxoaporphines have been isolated from the following plant species the three marked with asterisks being new alkaloids Alphonsea mo11is161 mollisine* (139) Annona ~acans'~~ liriodenine Fissis t igm a gla ucescensl liriodenine Guatteria foliosa" atherospermidine and 3-O-methyloxoputerine* (140) Lindera megaphyl1alo dicentrinone Lindera myrrha126 oxoducine* (141) Pip to stigma fugaxl 29 liriodenine lysicamine and 0-methylmoschatoline Step han ia abyssin ical O dicentrinone.The antimuscarinic action of liriodenine has been studied.162 OMe OMe 17.7 Dioxoaporphines Tuberosinone N-P-D-glucoside has been isolated from Aristolochia ~innabarina.'~~ Pontevedrine (143) has been synthesized by a radical-induced cyclization of the 6'-bromo-benzylisoquinolin-3-one (142) followed by oxidation and N-methy1ati0n.l~~The same synthesis using a photo-induced cyclization was previously reported in 1978.17.8 Aristolochic Acids and Aristolactams Aristolochic acids and aristolactams have been isolated from the following plant species the four marked with asterisks being new alkaloids Annona ~acans~~~ aristolacams A11 and BII Aristolochia cinnarb~rinal~~, 165 16' aristolochic acids A A11 and AIII aristolochic acid AIIIa 6-P-~-glucoside*(144) aristolactam aristolactam N-P-d-glucoside* (145a) cepharanone A N-p-D-glU-coside* (145b) and 2-hydroxy-8-methoxycepharanone A* (146) Aristolochia ~ontortal~~ 7-hydroxyaristolochic acid A 7-methoxyaristolochic acid A aristolochic acid C and aristolactam N-p-D-glucoside Piper puberulum168 'piperolactam S' which is the previously known saurisolactam .":* Jy HO OH 0 (145a) R=OMe (145b) R=H 17.9 Oxoisoaporphines The oxoisoaporphine alkaloids dauriporpine menisporphine (147a) and 6-O-demethylmenisporphine (147b) have been isolated from Menispermum dauricum.The last of these is a new NATURAL PRODUCT REPORTS 1996 alkaloid the structure of which was determined from its spectra and from its conversion into meni~porphine.~~ MeO OMe (147a) R = Me (147b) R=H 17.10 Azafluoranthenes and Related Alkaloids Grandirubrine (148a) and pareirubrine A (148b) have been isolated from Abuta ~oncolor.~~~ O-Methylation of these has given O-methylgradirubrine (imerubrine) (148c) and O-methylpareirubrine A (148d) respectively together with the isomeric bases isoimerubrine (149a) and O-methyl-isopareirubrine A ( 149b).169Nucleophilic substitution of OMe by SMe in imerubrine and isoimerubrine has given the thio-analogues (150) and (1 51).169 OMe Me0 %R2 M e 0 9 -\ I Me0 0N OR1 / \ R2 0 (148a) R' = R2 = H Y OR o (148b) R' = H R2 = OMe .I (148c) R' =Me; R2= H (149a) R' = Me; R2 = H (148d) R' = Me; R2 = OMe (149b) R' = Me; R2 = OMe OMe OMe A synthesis of the azafluoranthene alkaloid imelutine (156) has been achieved by condensation of the bromo compound (152) with the boronic acid (1 53) to give the biphenylaldehyde (154) base-catalysed condensation of this with nitromethane OMe !(OH) MeO@CHO @CONPi2 Me0 OMe NATURAL PRODUCT REPORTS 1996-K.W. BENTLEY and reduction of the resulting nitrostyrene to the biphenyl- Me0 ethylamine (1 59 followed by Bischler-Napieralsky cyclization and dehydrogenation of the product.17* rearranged to grandirubrine (148a).17' (160) (161a) R' = H; R2 = C02Me (161b) R' = R2 = Me (161c) R' = Me; R2 = C02Me ?Me OMe Ye charge to give (162). In the absence of a suitable nucleophile as under anhydrous conditions or in the presence of the Me0rH2Me0 CONPri2 Me0 - Me0 sterically restrictive tert-butanol the intermediate reverts to (160). In support of this mechanism it was found that 5- A first synthesis of a tropolone alkaloid of this group has been achieved. The keto-ketal(157) on heating with trifluoro- acetic acid was converted into imerubrine (148c) and the diketone resulting from the hydrolysis of (1 57) spontaneously Meov \ / OMe \ / OMe Me0 OMe OMe OMe 18 Alkaloids of the Morphine Group Alkaloids of the morphine-morphinandieneone group have been isolated from the following plant species the two marked with asterisks being new alkaloids Litsea a~urninata~~ pallidine Papa ver pin nutifidum oripavine and thebaine Stephania aculeata26 amurine Step han ia cep haran tha4' cephamonine* (1 58) cephamunine* (1 59) and sino- menine OMe OMe (158) (159) The structures of the new alkaloids were determined by comparison of their spectra with those of ~inomenine.~' A review of the variation of the production of morphine in a variety of strains of Papaver somniferum over a period of thirty-seven years has been published.172 The enzyme codeine reductase which catalyses the reduction of (-)-codeinone and (-)-morphinone into (-)-codeine and ( -)-morphine has been isolated from Papaver somniferum.This enzyme also catalyses the reduction of dihydrocodeinone dihydomorphinone naloxone and naltrexone stereospecifically to the 6a-hydroxy compounds but does not catalyse the reduction of neopinone or of ~a1utaridine.l'~ N-methoxycarbonylnorcodeinone(160) has been found to be stable to irradiation in dry benzene but in the presence of water methanol or ethanol it is photolysed to the ketones (162a) (162b) or (162c) though photolysis in the presence of the more bulky tert-butanol was unsuccessful.The reduced compound N-methoxycarbonylnordihydrocodeinone was stable under all conditions. These transformations have been explained as involving production of the intermediate spirodienone (161a) which suffers opening of the cyclopropane ring by nucleophilic attack by RH at the carbon atom most able to bear a positive methylcodeinone (1 63a) is photolysed under all conditions even in the absence of a nuleophile to the cyclic ether (165a) whereas the N-methoxycarbonyl analogue (1 63 b) gives a mixture of the dienone (164b) and the cyclic ether (165b) and of these two the former was converted into the latter in triethylamine. The collapse of (1 61 b) and (161c) to (1 64a) and (I 64b) and the cyclization of (1 64) to (1 65) is easy to understand.Similar products were obtained by the photolysis of 5-methylmorphinone and 5-methyl-1 4-hydro~ycodeinone."~ Me0 NCOfle 0- 0 (162a) R = OH (163a) R=Me (162b) R = OMe (163b) R = C02Me (162~)R = OEt (162d) R = OAC (164a) R=Me (165a) R=Me (164b) R = C02Me (16%) R = C02Me When (160) is photolysed in the presence of acetic acid rather than alcohols the formation of (162d) is accompanied by the formation of the enamide (166) in one chiral twist form only and this is the sole product of photolysis in tetrahydrofuran plus oxalic acid. Catalytic reduction of the enamide and reduction of the N-C0,Me group of (166) with lithium aluminium hydride gave the tertiary base (167).174 HO Prolonged irradiation of (1 60) in aqueous tetrahydrofuran gave both diastereoisomers of the tetrahydrofuranyl-ketone (168) as well as the alcohol (162a) and the dihydrocodeinone derivative (169) which is stable to rearrangement was a minor product in some experiments in tetrahydrofuran plus oxalic acid.174 ’j’H Irradiation of (I 60) and of (1 63b) in the presence of methanol with increasing amounts of triethylamine resulted in the production of (1 62b) and (1 65b) together with increasing amounts of N-methoxy-carbonylnorthebainone(1 70a) and its 5-methyl analogue (1 70b) in yields rising to 60 YOwhen methanol was e~c1uded.l~~ [In the original paper these bases are referred to as derivatives of a-thebainone which is a misnomer.They are derivatives of thebainone which has the C-14 hydrogen on the p-face of the molecule in conventional representations and is the C-14 epimer of /3-thebainone which has the same hydrogen on the a-face.The name a-thebainone was given175 to a ketone of unknown structure obtained by the hydrolysis of ‘phenolic dihydrothebine’ and later176 shown to have the structure (171).] In these processes small amounts of the 7,8- dihydro-ketones (172a) and (172b) were also obtained. These transformations clearly represent reductions with opening of the 4,5-oxygen bridge of (160) or of the cyclopropane ring of (161) or the saturation of the 7,s-double bond the hydrogen atoms being supplied by the transfer of protons or hydrogen atoms from the radical cation of trieth~1amine.l~~ (170a) R=H (17%) R=Me (172a) R=H (17%) R=Me The structures of the compounds obtained in these photolyses are based on detailed spectroscopic studies on X-ray crystallo- graphic studies of the enarnide (166) and the ketone (173) NATURAL PRODUCT REPORTS 1996 resulting from the reduction of (162b) and on the comparison of (1 70a) with authentic derivatives of thebainone and p-thebain~ne.’~~ The photolysis of codeine in the presence of oxygen has afforded N-formyl norcodeine and codeinone.177 /3-Chlorocodide (1 74a) and bromocodide (1 74b) have been shown to react with lithium cyanoalkyl- and cyanoaryl-cuprates by allylic substitution with and without inversion to give bases of general structure (175a) (both isomers) and the isomeric codeine and isocodeine 6-O-methanesulfonates (1 75b) react with the same reagents without allylic rearrangement to give the same Treatment of P-chlorocodide (1 74a) with tetra (triphenylphosphinyl) palladium has given 6-demethoxy- thebaine the n-palladium complex of which gave (175c) and (175d) on treatment with methyl- and phenylzinc halides.179 (174a) R = CI (175a) R = alkyl aryl (174b) R=Br (17%) R = OSQMe (17%) R= Me (175d) R=Ph When 3-O-benzylnaltrexol (1 76) was treated with large halides such as 2-bromomethylnaphthalene and 9-chloromethylanthracene potassium hydroxide and tetra-butylammonium bromide under phase-transfer conditions the novel 6,14-cyclic ether (177) was formed.lsO fPh fPh The indolocodeinone ketal (178) when heated with chloro- acetic acid gave the diene (179) and the ester (18O).ls1 The quaternary salt of (1 78) rearranged on hydrogenation to give (181) and its 9,14-unsaturated isomer.182 Meo-H 0 oMej) ~ ~ M e (1 73) NATURAL PRODUCT REPORTS 1996-K.W. BENTLEY Aerial oxidation of thebaine in the presence of tetra-phenylporphyrin yielded the keto-aldehyde (1 82) believed to be formed from the peroxide (183) which could not be isolated although its N-methyl salt could be prepared by the oxidation of thebaine methiodide and was hydrolysed to 14-hydroxycodeinone methiodide. Collapse of the peroxide (1 83) to the iminium salt and oxidation of the enamine derived from this could account for the production of (182).183 Diels-Alder reactions of thebaine have been achieved with dienophiles of general type (184) generated in situ from Mannich bases derived from cyclobutanone cyclopentanone cyclohexanone indan-1-one and the isomeric a-and p-tetralones to give adducts such as (185) (186) and (187) with both configurations at the asymmetric carbon atom so created.The addition of indenone afforded both (188) and (189).18* The adducts (190) have been prepared from P-dihydrothebaine and the appropriately substituted quinones (191).lS5 0 Me0'*? Me0 Me0 0 Me Me0 \/ Meom (189) (190) R' = NHAc SCH&H2C02H SCH2CH2OH; R2 = H Me 141 Details have been given of the purification of codeine prepared by the methylation of morphine,ls6 and of preparations of the following 3-0-(2-hydroxyethyl)- and 3-0-(morpholinoethyl) normorphine and their N-alkyl substituted analogues ;le7 6-0-p-guanidinophenylmorphine ;Ie8 l-bromo-and 1-chloro-nor-morphine and their N-substituted derivatives;lSS 6-0-alkylnormorphines;1so6P-amino- 14p- hydroxydeo~ymorphine~~~ and its 7,8-dihydro derivative;lS2 7-phenyldihydrocodinone ;lS3 phosphate esters of naloxone and of naltrexone;lS4 ethers of naltrexone oximelg5 and of naltrexol ;lgSnalbuphine ;lo'N-cyclopropylmethyl-5-methyl-14-methoxydihydronormorphinone;lS87-spiroindanodihydronor-morphinone and its N-substituted derivatives;ls9 the azines (192a) (192b) and (192~);~~~ the pyrrole (193);201 the indole (194a) and related the indole (195) ;204 the derivatives of the benzofuran (1 94b) ;205 7,7'-methylenebis-dihydrocodeinone and the pyridine (196) derived therefrom ;206 the bases (197)207 and (198);208northebaine (by microbiological 03-i NMe HNWMe (192a) R' = R2 = H (193) (192b) R' =H; R2=OH (192~)R' = R2 = OH HO Me0 X Me Me '2''8 z (194a) X=NMe (1 95) (194b) x=o 0 R2vo0 A' (191) R' = NHAc SCH~CH~COZH SCH2CHflH; R2 = H Me NATURAL PRODUCT REPORTS.1996 N-demethylation of thebaine) ;20s Diels-Alder adducts of n~radrenalin,~~~.rnet-enke~halin,~~~ 324 and luteinizing 6-thebaine and of northebaine with methyl vinyl ketone;210*211 hormone;326on liver lipids;327 on the conversion of dynorphins 0-demethyletorphine2l2 and tritium-labelled b~prenorphine.~~~ into enkephalins;328 on the activity ofpro-enkephalin messenger Details have also been given of the conversion of morphine into RNA;329 on the formation of super~xide;~~~ on oxidative 10-0-methylapomorphine and 1O-deoxyap~morphine,~~~ metaboli~m;~~' 333 and on of the on the neurotoxicity of gl~tamate;~~~, Hofmann degradation of the base (199)214and of a crystallo- the effects of brad~kinin,~~~ diazepam335 and isofl~orane.~~~ graphic study of b~prenorphine.~'~ Recent pharmacological studies of morphine have been reviewed.337 The morphine-antagonist properties of naloxone have been as have the effects of this compound on Meon behaviour ;251.341-344 on the cardiovascular on the gastro-intestinal tract;351 on bone marrow cells;352 on the aggregation of platelets ;353 on adenosine receptors ;354 on on retinal i~chaemia;~~~ cerebral i~chaemia;~~~ on the con-sumption of oxygen ;3573 358 on oxidative on post-asphyxia cerebral pathology;35s on fever induced by Methods of estimating morphine,216 normorphine,216 co- 21s+ deine,216-218 and the glucuronides of these,216* 220 and nalbulphine221 in body fluids have been described.T,he phenolic hexahydroisoquinoline (200) suitably protected has been oxidized with chromic acid to the (protected) ketone (201a) which was converted by the Wittig reaction into the diene (20 1b). Cyclization of this phenol with di(trifluoroacetoxy)di(triphenylphosphinyl)palladium then afforded (202) which was oxidized successively with osmium tetroxide and periodic acid to give N-methoxycarbonyl- dihydronorcodeinone (203a).Since this is easily converted into dihydronorcodeinone (203b) which was an intermediate in the first recorded synthesis of morphine this approach constitutes a formal synthesis of the alkaloid.222 MeoQ MeoQ HO HO 0 xfikC02Me (201a) X=O (200) (201b) X=CH2 NC02Me (203a) R = C02Me (203b) R=Me lipopolysaccharides ;360 on levels of insulin32o and glucose ;320 on and the uptake of 2-deoxyglu~ose;~~~ on the effects of amphetamine.362 The pharmacological properties and physiological effects of the following have also been studied morphine 3-0-glu~uronide;~~~. 366 364 morphine 6-0-gl~curonide;~"~ 3,643-diacetylmorphine ;367 dihydromorphine ;368 dihydromorphine 6-0-glucuronide ;368 codeine;218.36s-371 codeine 0-glucuronide ;368 di hydrocodeine ;3 72 3-0-ethylmorphine ;37 N-propyl-14-hydroxynordihydr~morphinone;~~~ dihydrocodeinone hy-drazone and xim me;^'^ 14-hydro~ydihydrocodeinone;~~~ nal-oxone benzylh~drazone;~~~ 3-0-methylnaloxone xim me;^^^ naltrexone ;377-385 naltrexone methiodide;386 3-0-methyl- nalmefene:3s1* naltrexone ;387-389 nalb~phine;~'~ 3s2 p-funal-trexamine ;3s3 naltrindole ;394-3s6 N-benzylnaltrindole ;3s7 401 norbinaltorphimine ;3s8 oripavine ;3ss ~inomenine;~~*-etor-phine ;2s7. 402. 403 dihydroetorphine ;404-407 diprenorphine ;408-410 and bupren~rphine.~~~-~~~ 19 Phenethylisoquinolines The structures of isoautumnaline (204) and dysoxylin (205) have been confirmed by syntheses of their racemates by the Bischler-Napieralsky route.41s H Me0 e Me0 o yHe*M e Treatment of the N-oxide of 0-methylandrocymbine (206a) with acetic anhydride gave principally N-acetyl-0-A review of the recent chemistry of the alkaloids of this methylnorandrocymbine (206b) in chloroform but in triethyl- group has been amine the main product was the enamine (207) which was The analgesic propertie~~~~-~~~ of and pharmac~kinetics~~~-'~~ morphine have been studied as have the effects of the alkaloid on behaviour ;253-271 on immune responses ;272-27s on neur-ones ;280-286 on the gastro-intestinal tract ;287 on locomotor OMe OMe activity ;288.28s on respiration ;2s0 on mem~ry;~~~-~~~ on taste perception;2s4 on the reproductive ~y~tem;~~~.~~~ on the heart MeO on the tra~haea;~~~on lymphocytes ;2ss-300 on mitochondria1 activity ;301 on metastasis induced by surgery ;302 on inflammati~n;~~~,~~~ on the synthesis of proteins;305 on the thalamus ;306 on messenger RNA ;307.308 on adrenergic recep- MeOM@> 0 R tor~;~~~on the activity of protein kinase310 and metallo- proteinase ;311 on levels of a~etylcholine,~'~ d~pamine,~'~?315 serotonin,316-317 cat echo la mine^,^^^. 31s gl~cagon,~~Osomatostatin,320 insulin,32o. 321 growth (206a) R=Me (206b)R = AC NATURAL PRODUCT REPORTS 1996-K. W. BENTLEY converted by N-bromosuccinimide in water plus ethylene glycol into the bromo-lactam (208).420 Enzymatic resolution of racemic O-acetylhomoaporphines with deacetylation has been achieved in reasonably good yield by immobilized lipase in organic OMe Me0 Me 20 Colchicine and Related Alkaloids Colchicine 2-O-demethylcolcicine 3-O-demethylcolchicine N-formyl-N-deacetylcolchcine,colchifoline demecolcine and 2-O-demethyldemecolcine have been isolated from Colchicum megaph y lla.42 9-O-Methylisocolchicide (209a) on heating with methyl mercaptan in methanol or dimethyl sulfoxide has been converted into the isomeric methylthio-compounds (209b) and (209~).~~~ N-Acetoacetyl-N-deacetylthiocolchicinehas been prepared for biological Patents covering the prep- aration of derivatives of (2 and (2 1 1)426 and their possible use as pharmaceuticals have been published. Me0 e O q M R2 R1 0 (209a) R' =OMe; R2= H (20%) R' =SMe; R2= H (20%) R' = H; R2 = SMe The effects of colchicine on leukaemic cells;427 on lung fibrosis;428 on the production of inter leu kin^;^^^ on multi-drug resistance;430 on the metabolism of carbohydrates ;431 on smooth muscle cells;432 and on the control of blood pressure433 have been studied as have the pharmacological prbperties of thiocolchicine.434 21 Erythrina and Related Alkaloids 21.1 Erythrina Alkaloids Alkaloids of this group have been isolated from the following Erythrina:berter~ana~~~ alkaloids plant species the two marked with asterisks being new erythratine N-oxide" (2 12) Erythrina caflra436 erysodine erythraline erythratine erythrinine (2 13a) and epierythrinine* (213b) 143 0 0 OH MeO' (2 1 2) (213a) R' =OH; R2= H (213b) R'=H; R2=OH (213~)R' = OAC; R2 = H (213d) R' =OMe; R2 = H The structure assigned to erythratine N-oxide was confirmed by its preparation by the oxidation of erythratine.Diels-Alder addition of 1-methoxy-3-trimethylsilyloxy-butadiene to the keto-enamide (214) gave a mixture of epimers of the tetracyclic compound (21 5). Protection of one of the keto groups as the cyclic ketal followed by reduction of the other hydrolysis of the ketal and elimination of methanol then gave the keto-ester (2 16a). This was selectively hydrolysed and decarboxylated to (216b) the methanesulfonyl ester of which on heating with calcium chloride in dimethyl sulfoxide gave the dienone (217). Reduction of this with sodium borohydride then gave the dienol (218a) together with its epimer and O-methylation of (21 8a) gave racemic erysotramidine (21 8b) which was reduced to erysotrine (219).437 The oxidation of suitable intermediates in this synthesis with ceric ammonium nitrate in acetic acid and in methanol has afforded syntheses of racemic O-acetylerythrinine (2 13c) and erythristenine (21 3d).438 Condensation of (220) prepared from L-DOPA with oxalyl chloride followed by cyclization with boron trifluoride gave a mixture of diastereoisomers of the keto-ester (221) one MeoqMe Me0 0 0 C02Me Me02C 0 OMe (216a) R = C02Me (216b) R = H MeO Me0 RO'.MeO'. (2184 R = H (218b) R = Me C02Et Me0 CGEt ~::Tco~E~ MeOvit 0 u 0P (220) (221) of which was converted through the alcohol (222) into (-)-3- deoxyerythratidinone (223) by conventional processes.43g Me0 Me0 OH 21.2 Cephalotaxine and Related Alkaloids Two new syntheses of cephalotaxine have been reported.The known iodopiperonyl-ethanol (224) was protected as the tert-butyldimethylsilyl ether and converted into the ortho-lithium salt and formylated to give the aldehyde (225) which on treatment with 1,2-bis(trimethylsilyloxy)cyclobutaneand boron trifluoride followed by acid-catalysed pinacol-pinacolone transformation gave the enol ether (226). Reaction of this with the Grignard reagent (227) gave the acetal (228) which was converted into the 0-methanesulfonate ;this was hydrolysed to the aldehyde which was reductively aminated to the amine (229). Cyclization of this amine gave (230a) which was debenzylated and converted into the N-tert-butyloxycarbonyl derivative (230b).This was oxidized by [(-)-camphor-10-sulfonyl]oxaziridine to the ketol (23 1) and further oxidized by dimethyl sulfoxide to the enedione (232). Removal of the butyloxycarbonyl group from (23 1) was accompanied by cyclization to racemic demethylcephalotaxinone (233) from which cephalotaxine (234) was prepared earlier. OMes 0 (230a) R = CH2Ph (230b) R = CO~BU' 0 (232) NATURAL PRODUCT REPORTS 1996 A stereospecific synthesis of (-)-cephalotaxine has been achieved from the D-proline derivative (235). This was converted through (236a) (236b) and the ester (237) into the ester (238a). Conversion of this into the aldehyde (238b) followed by cyclization with tributyltrimethylsilyltin gave the alcohol (239) and cyclization of this with polyphosphoric acid gave the tratracyclic base (240a) which was converted through (240b) into (240c).Oxidation of this with osmium tetroxide gave the diol(241) oxidation of which yielded the dione (242). Treatment of the dione with ethyl orthofonnate and toluenesulfonic acid gave the ketal (243) and elimination of methanol from this followed by reduction of the resulting enone with sodium borohydride then gave (-)-~ephalotaxine.~~l to Me0 Me0 (235) (236a) R = SiMe (236b) R=I (238a) R = C02Me (239) (238b) R = CHO (240a) R' = R2 = Me (24Ob) R' = R2 = H (240~)R' R2 = CH2 0 (242) (243) Esters of cephalotaxine with amino acids have been prepared as potential antileukaemic agents.442 22 Other lsoquinoline Alkaloids The new alkaloid tamynine (244) of uncertain biogenetic origin has been isolated from Murruyu paniculat~.~~~ 23 References 1 G.Ruecker E. Breitmeier G. L. Zhang and R. Mayer Phyto-ij OMe chemistry 1994 36 519. (233) (234) 2 X. Jin and K. R. Cui Yaoxue Xuebao 1994 29 122. NATURAL PRODUCT REPORTS 1996-K. W. BENTLEY 3 S. D. Fazylov A. M. Gazaliev R. Z. Kasenov and M. Zh. Zhurinov Zh Obshch. Khim. 1994 64 874. 4 K. M. Turdybekov S. D. Fazylov R. Z. Kasenov A. M. Gazaliev and Yu. T. 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ISSN:0265-0568    

DOI:10.1039/NP9961300127

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Triterpenoids Joseph D. Connolly and Robert A. Hill Department of Chemistry Glasgow University Glasgow G 12 8QQ,UK Reviewing the literature published during 1994 (Continuing the coverage of literature in Natural Product Reports 1995,Vol. 12 p. 609) 1 Introduction 2 The Squalene Group 3 The Fusidane-Lanostane Group 4 The Dammarane-Euphane Group 4.1 4.2 Tetranortriterpenoids Quassinoids 5 6 7 The Lupane Group The Oleanane Group The Ursane Group 8 9 10 The Hopane Group Miscellaneous Compounds References I Introduction This article follows the pattern of the previous report. A review of the 13C NMR data of 396 pentacyclic triterpenoids has been published.’ The reaction of triterpene carboxylic acids and acetobromo-sugars under phase transfer conditions is reported to give the corresponding p-D-glycosyl esters in good yield.2 2 The Squalene Group A switching of the modes of cyclization of squalene-2,3-oxide has been observed when cultures of Tubernaemontana divaricata are treated with elicitors.The enzyme squalene-2,3-oxide amyrin cyclase was induced whereas squalene-2,3-oxide cycloartenol cyclase was inhibited.3 The cyclization of 2,3-dihydrosqualene and squalene-2,3-oxide by squalene cyclase has been ~tudied.~ 3 The Fusidane-Lanostane Group Several new protostanes have been isolated from Alisma orientale including 1 1-deoxyalisol A (I) 25-0-methylalisol A (2) 16-oxoalisol A (3) 1 l-deoxy-l3P 17P-epoxyalisol A (4) 13/3,17/?-epoxyalisol A (5) 25-anhydroalisol A (6) 11-deoxyalisol B (7) and the corresponding 23-acetate (8) 11-deoxy- 13P 17P-epoxyalisol B 23-acetate (9) 13p 17P- epoxyalisol B (10) and the corresponding 23-acetate (1 I) 16P,23-epoxyalisol B (1 2) alisol C (1 3) and 1I-deoxyalisol C 23-acetate (14).5 The structures of 13~,17~-epoxyalisol B 23-acetate (1 1) and the already known alisol D were confirmed by X-ray analysis.OH 1 (1) R’ =H; R2=H,H; R3=H (2)R’ =OH; R2= H,H; R3=Me (3) R’ =OH; R2=0; R3= H (4) R’ = H; R2 = H,H; R3 = H; 13p,l-Ip-epoxide (5) R’ = OH; R2 = H,H; R3 = H; 13P,l-Ip-epoxide OH (7) R’ = R2= H; R3 = H,H (8) R’ = H; R2=Ac; R3= H,H (9) R’ = H; R2 = Ac; R3 = H,H; 13P,17f+epoxide (10) R’ =OH; R2 = H; R3 = H,H; 13p,17&epoxide (1 1) R’ = OH; R2 = Ac; R3 = H,H; 13p,17&epoxide (13) R’ =OH; R*=H; R~=O (14) R’ = H; R2=Ac; R3=0 The ring-contracted lanostanes natalic acid (15) and albertic acid (16) have been isolated from Phellinus torulosus together 0 151 NATURAL PRODUCT REPORTS 1996 with the pentanorlanostane torulosic acid (17)? The pentanor- 24-methylenelanost-8-en-3-one (24) 24-ethylidenelanost-8-en-lanostane posietogenin (18) is the genin of cucumarioside G 3/3-01 (25) and the corresponding 3-ketone (26) from Neolitsea from Eupentacta fraudutrix.' Pistacigerrimone E (19) is a 13,14- sericea;I2 24-ethylidenelanost-9(1 l)-en-3/3-01 (27) from Pisum secolanostane from Pistaciu integerrima where it is found with 0\ \ 3-oxolanosta- 1,5,8,24-tetraen-26-oic acid (20) which is named pistacigerrimone D.* 3O-Norlanost-8-en-3,8-01 (2 1) has been isolated from Pseudoceratina crassas and the 24-methyl-30- norlanostane derivative (22) is the genin of uloside A from a OH 1 HO COOH (22) sponge of the Ulosa species.l0 Several other new 24-alkyllanostanes have been reported including the 29-norlanostane obtusifolione (23) from Euphorbia piscatoria;ll (24) R' = 0;R2= H (25)R' = P-OH,H; R2= Me (26) R' =O;R2= Me sutivus ;13 15a-hydroxy-24-rnethylenelanosta-7,9( 1 1)-dien-3- one (28) from Desmos longiJtorus,l4and the hemiacetal(29) from Pisolithus tinctori~s.'~ Other new lanostanes include schisanol NATURAL PRODUCT REPORTS 1996-5.D.CONNOLLY AND R. A. HILL Reagents i MeAICI,; ii AcCI DMAP Scheme 1 (30) from Schisandra sphenanthera16 and applanoxidic acids E (31) F (32) G (33) and H (34) from Ganoderma applanatum.” Eryloside E is a saponin from the sponge Erylus gofsrilleri with the 24,25-dimethyllanostane (35) as genin.18 Other new saponins include formoside from Erylus formos~s~~ and saponins from Scilla peruviana Eucomis bicolor and Chiondoxa luciliae.2Q A carbocation-olefin cyclization route to the lanosterol series has been reported (see Scheme l).zl OnCrnH (31) R = P-OH,H (32) R=O (33) R’ = R2 = 0; R3= P-OH,H (34) R‘ = P-OH,H; R2 = a-OH,H; R3 = 0 \PH (35) The norcycloartanes 1 la-hydroxybuxatenone (36) and buxahejrine (37) have been isolated from Buxus papillosa.22 0@ (36) MeOOC@ Foetidinol (38) from the Chinese crude drug shengma (from Cimicifuga foetida) has an unusual 16,24-cycl0-25,26,27-trinor ~tructure.~~ Foetidinol (38) also occurs as its 3-0-/3-~-xylopyranoside cimicifugoside H-4 in Cimicifuga simplex together with cimicifugosides H-1 (39) H-3 (40)24 and the 7p- hydroxyshengmanol derivative (41).25The spiroacetal (42) has 5 HO HO OH HO (37) NATURAL PRODUCT REPORTS 1996 been found in Abies marocana together with the lactones (43) and (44).26 The sulfate esters (45)-(47) are constituents of Tydemania e~peditionis.~' Other new cycloartanes include OH 5 (43) (44) 24,25-didehydro 05 (53) (45) R=H,OH (46) R=O (47) R = 0;24,25didehydro O cycloartan-29-01 (48) and cycloartane-3/3,29-diol (49) from )c*H '.-OH (54) Mangifera indica,28 (23Z)-cycloart-23-ene-3/3,25-diol (50)from Juncus e#u~us,~~ 1) from 24-hydroperoxycycloart-25-en-3/3-ol(5 IH (48) R = H (49) R = OH 0 (55) CycloalpigeninA (56)is found in Astrogalus alopecurus together with its 3-O-/3-~-xylopyranoside,cycloalpiosideA.34Juncoside I from Juncus efusus has the new genin (57)35 and the 22- configuration of the known genin (58) of co-occurring OH OH OOH Euphorbia cypari~sias,~~ (24Z)-24-ethylidenecycloartanol (52) from the oil of the sea buckthorn (Hippophae rharnnoide~),~~ 24,25-dihydroxycycloartan-3-one(53) as a mixture of isomers from Artocarpus heterophyllu~,~~ 28-hydroxymangiferic acid (54) from Mangifera indi~a,~~ and 3,11,23-trioxocycloarta-1,7,16,24-tetraen-26-oic acid (55) from Pistacia integerrima.' NATURAL PRODUCT REPORTS 1996J.D. CONNOLLY AND R. A. HILL juncosides 11-V has been established as S.36 Other new HO cycloartane saponins include agroastragalosides I and I1 %.LR from Astragalus membranace~s,~~ alexandroside I from Astra-galus alexandrin~s,~~ cimisides C and D from Cimicifuga GlcOPH-OH dah~rica,~~ mussaendosides 0 P and Q from Mussaenda pubes~ens,~~’ 41 thalictosides I11 and IV from Thalictrum s~p.,~~ and saponins from HO ‘ tomentoside from Astragalus tomento~us~~ 7 Cimicifuga dahur i~a,~~ Cimicifuga foet ida,45 Cimicifuga sim- 6 ple~~~ and Heinsia ~rinata.~~ The structure of cucurbitacin Q from Cucumis spp.has been revised to cucurbitacin F 25-acetate (59)48and detailed NMR study of 23,24-dihydrocucurbitacinF (60) from Hemsleya amabilis has revealed errors in previous assignment^.^^ New cucurbitacins include rosacea acids A (61) and B (62) from (65) R =k& Russula ro~acea~~ and 3P-hydroxycucurbita-5,24-dien-7-one (63) from Trichosanthes kirilowii.,l 0 (66) R = \woAc ; 6,7-didehydm (67) R =kh (68) R = k h (59) R=Ac (60)R = H;23,24-dihydro (69) R=\* (70) R = ; 6,7-didehydro \% 0 (72) R = \*m ; 6,7-didehydro (73) R=\%~H OH HO” (74) R = ; 6,7-didehydro (61) R=OH (62) R=H HO /\ The group of ring-A-aromatic norcucurbitacins continues to expand with several duplication of names (see Nat.Prod. Rep. 1995 12 614). Cayaponia tayuya has been reported5’v5’ to contain cayaponosides A (=the known fevicordin B glu-coside) A (64),A (65),A (66) A (67) B (known) B (68) B (69) B4( 5the known andirobin A glucoside) B (70) C ( = the known fevicordin D glucoside) C (= the known andirobin B glucoside) C (71),C, ( = the known fevicordin C glucoside) C, (72) D (known) D (73) and D (74). OH Cabenosides A (75)and B (76) have been found in Caputo nigra \*w together with cabenoside C which has also been called (75)R’ = R2 = Glc; R3 = caraponoside C and andirobin B glu~oside.,~ Andirobin A OH gentiobioside (77) and andirobin C gentiobioside (78) have Full details of the (76) R’ = Glc(l42)Glc; R2 = H; R3 = been isolated from Fevillea tril~bata.~ OH structures of cayaponosides A BBa B6b C, D and Dabfrom Cayaponia tayuya (see Nat.Prod. Rep. 1995 12 615) have (77) R’ = Glc(l+6)Glc; R2 = H; R3 = been p~blished.,~ OH (78) R’ = Glc(l46)Glc; R2 = H; R3 = \* 4 The Dammarane-Euphane Group Dymalol(79) is a ring-A cleaved dammarane from Dysoxylurn malabaric~m~~ whereas ring D is cleaved in the rearranged genin (80) of mabioside C which is found in Colubrina elliptica together with mabiosides D and E whose genins are (81) and (82) respe~tively.~~ The unusual 25-ethyl-24-methyldammarane derivatives (83) and (84) have been isolated from Pilocarpus NATURAL PRODUCT REPORTS 1996 Panax vietnamensis include the new genins (87)-(90).61 Other new dammarane saponins include bacoside A from Bacopa monniera,62 vinaginsenosides R3-R9 from F'anax vietnah-en~is,~~ and zizyphoisides C-E from alphitonia zi~yphoides.~* The 3D structure of ginsenoside Rb has been studied using 2D NMR.65 (88) R =OH (89) R=H +OH HO Eupha-7,24-diene-3,8,1Ip,16a-trio1 (91) has been isolated from Garuga pinnataG6 and the tirucallane derivative lipo-3- episapelin A (92) from Trichilia c~nnaroides.~~ Delevoyin A (93) is a secotirucallane from Entandrophragma delevoyP and Aglaia leucophylla is the source of the related derivatives (94) and (95).69 The glabretal derivative 3-oxoskimmiarepin (96) has HO #-OH ,. (92) n= 10,12,14,16 R1om*A - R (93) R' = H; R2 = Me (94)R' = H; R2 = COOH (83)R = P-OAC,H (84) R = 0 (85) R=a-OH,H (86) R=O (95) R' =Me; R2 = COOH pic at us^^ and dammar-24-ene-301,ll a,22<-triol (85) and the 0 corresponding 3-ketone (86) have been found in Astrotrichilia asterotricha.60The structure of (84) was confirmed by X-ray crystal structure analysis.59 Vinaginsenosides RlO-R14 from NATURAL PRODUCT REPORTS 1996J.D. CONNOLLY AND R. A. HILL Two related com-1995 12 618) has been found in A. indi~a.~~ been found in Zanthoxylum peti~lare.~~ The Meliacarpin pounds dysoxylic acids A (97) and B (98) have been reported derivative (1 07) has been isolated from Melia a~edarach~~ Brucea javanica is the source together with azedarachin A (108) and the corresponding 2- from Dysoxylumpettigrewian~m.~’ of the apotirucallanes bruceajavanin A (99) dihydro-acetate (109) 12-acetylazedarachin B (1 12-acetyltrichilin bruceajavanin A (100) and bruceajavanin B (101).72 COOH R’ *‘OR2 (97) R’ = a-OAc,H; R2 = H (98) R’ =a; R2 = AC H ,.O ROW 0 ‘OAc (99) R =Ac (100) R = Ac; 1,2-dihydro (101) R=Me 4.1 Tetranortriterpenoids Brownins C (102) F (103) G (104) and H (105) are highly rearranged tetranortriterpenoids from Harrisonia bro~nii.~~.74 0 0 (105) Azadirachtin has been used for the automatic analysis of ‘H and 13C NMR correlation data using the Logic for structure determination (Lsd) ~rogramme.’~ The crystal structure analy- sis of azadiractin A from Azadirachta indica has been reported.76 The biosynthetic studies on nimocinol and nimocinolide from A.indica have revealed the expected biosynthetic path~ay.‘~ The 11-epimer (106) of azadirachtin H (see Nat. Prod. Rep. B (1 1 l) 1,12-diacetyltrichilin B (1 12) and trichilin H (1 13).81 Trichilins I (1 14) and J (1 15) have been found in Melia COOMe R’TcOO-H (108) R’ = Me; R2 = R3 = H; R4 = OH (109) R’ = Me; R2 = R3 = H; R4 = OAc (110) R‘ = R2 = R3 = H; R4 = OAC (111) R’=Me; R2=R4=OAc; R3=H (112) R’=Me; R2=R4=OAc; R3=Ac (113) R’ = R3 = H; R2 = R4 = OAC (114) R’ =Me; R2 =OH; R3= H; R4 =OAc (115) R’ =Me; R2 =OH; R3 = R4 = H toosendan.82 Trichila rubra is the source of rubrins A (1 16) B (1 17) C ( = the known hispidin A) D (1 18) E ( = the known nymania l) F (119) and G (120)s3 whereas 6-0-acetyl-2- hydroxy-3-0-tigloylswietenolide(121) is found in Trichilia R’ (116) R’ = P-OH,H; R2= om& (117) R‘ = @OH,H; R2 = OOGA (118) R’ = P-OH,H; R2 = OOCEt (119) R‘ =O; R2=OAc (120) R‘ = P-OH,H; R2 = OAC 0 MeOOC ‘OH ~onnaroides.~’Full details of the structure elucidation of carapolides C D E and F from Carapa grand$ora together with the new carapolides G (122) H (1 23) and I (124) have been “OAc (123) 14(3,15(3-epoxide (1 24) The structures of cedrelanolide I (125) from Cedrela salvad~rensis,~~ utilin C (1 26) from Entandrophragma utile,86 and cycloepiatalantin (1 27) from A talantia zeylanicaS7 were es- tablished by X-ray analysis.Atalantia zeylanica has also been found to contain cycloatalantin (1 28) dehydrocycloatalantin (129) and isocycloatalantin 17-P-~-glucopyranoside (1 30).87 MeOOG OAc (126) Q ! $.ZH (127) R =u-OH,H OH (128) R =P-OH,H (129) R=O Boronialatenolide (1 3 1) from Boronia alata is a pentanor-triterpenoid.s8 Other new limonoids include delevoyin B (1 32) HOa0 NATURAL PRODUCT REPORTS 1996 from Entandrophragma delevoyi,68 turraflorins A (1 33) B (1 34) and C (135) from Turraea fl~ribunda,~~ and the butanolides (1 36) and (1 37) from Chisocheton microcarpu~.~~ 0 (133) R=Ac (134) R=H AcO Q b ! AcO..0p 0 (135) (136) R =Ac (137) R =H 4.2 Quassinoids The structures of neosergeolide (138) from Picrolernma pseudo- cofseagl and peninsularinone (1 39) from Castela peninsularisg2 OH -..I 0 and the absolute configuration of brucein Hg3were confirmed by X-ray analysis. Other new quassinoids include indaquassins C (140) D (141) E (142) and F (143) from Quassia indicag4 and OH (141) R= H (142) R=OH 0 0 0 0 OAc NATURAL PRODUCT REPORTS 1996-J. D. CONNOLLY AND R. A. HILL ailanquassins A (144) and B (145) from Ailanthus malabari~a.'~ acid (1 5 1) from Betula pubescens.lo3 The X-ray analysis of Analysis of the NMR spectra of neoquassin from Quassia monogynal A has been reported.lo2 Cirenosides E-H are amara showed that both C-16 epimers are pre~ent.'~ The total saponins from Oplopanax elatus including the new genin 3a,23- synthesis of samaderin B has been rep~rted.~' dihydroxylup-20(29)-en-28-oicacid (1 52).lo4 Other new lupane saponins have been isolated from Oplopanax elatuslo5 and OH OH Scheflera lucan tha.lo6 5 The Lupane Group The 28-norlupane (146) has been isolated from the decaying bark of Betulaplatyphylla var.jap~nica.'~ The norlupane (146) is thought to be a biodegradation product of betulin. Holarrhenol from Holarrhena antidysenterica is lupa- 18,20(29)-dien-3P-o1 (147).99 Other new lupanes include lup-20(29)-ene-3a,27-diol (148) from Diospyros peregrina,loO 17-epi-lupenyl acetate (149) HO R' from Ixeris chinensis,'O' the p-coumaroyl ester of monogynol A (150) and the corresponding Z-isomer from Salvia montbretii,lo2 and the 3-caffeoyl ester of 3P,23-dihydroxylup-20(29)-en-28-oic (152) R &-OH 6 The Oleanane Group Villosagenins I (1 53) and 11 (1 54)Io7 and auriculatone (155)'"* are 28-noroleananes from Silene villosa and Aster auriculatus (153) R=CHO (155) R=Me respectively.The structure of auriculatone (1 55) was confirmed by X-ray analysis as was the structure of 13P,28-epoxyolean- 1 1 -en-3P-ol (1 56) from Minquartia guianensis.loS 3,4- Secooleana-4(23) 18-dien-3-oic acid (1 57) has been found in Euphorbia chamaesycel'O and the 17,22-~ecooleanane (158) in Hydrocotyle ranunculoides together with 1501,16a,2 1/?,22a- tetrahydroxyoleana- 1,12-dien-3-0ne (159) and the corre-sponding 1,2-dihydro derivative (160).11' 0 (159) (1 60) 1 ,Z-dihydro Thomandertriol from Thomandersia laurifolia is olean- 12- ene-2a,3a 19a-trio1 (1 6 1)lI2 and icacinic acid from Poraquciba guaianensis is 2a,3a 19a,23,24-pentahydroxyolean-12-en-28-oic acid (162) 113 Dillenic acids A (163) B (164) and C (165) and 3-oxooleana- 1,12-dien-3O-oic acid (1 66) have been isolated ....A HO..HO-*W R' R ' (161) R' = R2 = Me (1 62) R' = CH20H; R2 = COOH (163) R' = 0; R2= a-OH,H; R3 = H (164) R' = P-OH,H; R2 = 0; R3 = H (165) R' = 0; R2= H2; R3 = OH (166) R' = 0; R2= H2; R3 = H; 1,2-didehydro from Dillenia papuar~a.~~* Glypallidifloric acid from Glycyrrhiza pallidzj7ora has been identified as 3P-hydroxyoleana- 11,13( 18)- dien-30-oic acid (1 67).l15 Other new oleananes include 3p 19a,23,24-tetrahydroxyolean-12-en-28-oic acid (1 68) from HO HO Alibertia edulis,116 olean-12-ene-3P,1la,2la-triol (169) from Salvia nemo~osa,~~' 1la-hydroxyolean- 12-en-3-one (1 70) from Sabia schumanniana,lls 11a-hydroperoxyhederagenin (171) ..R2 R' (169) R' = P-OH,H; R2 =OH (170) R' = 0; R2 = H NATURAL PRODUCT REPORTS 1996 from Serjania triquetra,'lg atriplexinol (1 72) from Atriplex stocksii,"' 23-hydroxygermanicone (1 73) from Salvia pornifera and 1a,2a,3P,24-tetrahydroxyolean-12-en-28-oic OH (172) (1 73) acid (1 74) from Gentiana tibetica.'22 Rhoipteleic acid acids A (175) and B (176) from Rhoptelea chiliantha have a lignan portion esterified with 3P,27-dihydroxyolean-12-en-28-oic acid.123A biomimetic synthesis of rhoipteleic acid acids A (175) and B (176) has been achieved from 27-caffeoyloxy-3P-HO..x HOQ OH (175) R' = a-H; R2 = P-H (176) R' = P-H; R2= CL-H hydroxyolean- 12-en-28-oic acid (177) by oxidation with ferric chloride.The 3-caffeoyl ester of 3P723-dihydroxyolean- 12-en- 28-0ic acid (178) and the corresponding 23-caffeoyl ester have been found in Betula pubes~ens.''~ cooy HO (178) NATURAL PRODUCT REPORTS 1996-J. D. CONNOLLY AND R. A. HILL TFA __t Scheme 2 Yunganosides G 1 G2 H 1 H2,11,12 J 1,52 K 1 K2 L 1 and foleosides B-F include the new genin 2a,3p-dihydroxy-23- L2 are new sapogenins from Glycyrrhiza yunnanensis including oxoolean- 12-en-28-oic acid (1 85).12* the sapogenins yunganogen H (179) I ( = the known glyun- nansapogenin G) J (180) and K ( = the known melilo-tigenin).124Two oleanane saponins have been isolated from Myrsiize australis with the new genin 13p,28-epoxyoleanane- 3p,16cc,28&triol (18 1),125 and ardisicrenosides A and B from Ardisia crenata have the new genin 13/3,28-epoxyoleanane- 3p 16cc.30-triol (1 82).lZ6 Sitakisosides VI-X from Stephanotis HO (183) R=H2 (184) R=O A biomimetic polyene pentacyclization route has been used in the total synthesis of sophoradiol (olean- 12-ene-3P,22p- dioI).lz9 The key cyclization step is shown in Scheme 2.Efficient syntheses of glycyrrhetic acid gly~osidesl~~ and assignment of (179) R = CH20H (181) R’=OH; R2=H the 13C NMR data of maslinic acid131 have been reported. (180) R=CCQH (182) R’ = H; R2 = OH Two oleanolic acid saponins from the roots of Beta vulgaris contain the unusual feature of a 3,4-secoglycopyranosyl lutchuensis var.japonica include the new genins sitakisogenin moiety.132 Saponins given trivial names and with known genins (183) and the corresponding 22-ketone (1 84),127 and schef- are listed in Table 1. Table 1 New oleanane saponins Compound(s) Source Ref. Compound(s) Source Ref. Anagdllosaponins I-V Anagallosaponins VI-IX Aralosides H and J Ardisicrenosides C and D Anagallis arvensis Anagallis arvensis Alalia spinifolia Ardisia crenata 133 134 135 136 Escins Ia Ib Iia lib and Heteropappussaponin IIIa 2 Aesculus hippocrastanum Heteropappus biennis 162 163 Ardisicrenosides E and F Asperosaponins F and H Ardisia crenata Dipsacus asperoides 137 138 Heteropappussaponins 5 7 and 8 Hereropappus biennis 164 Asterbatanosides B and C Asterbdtanosides F and G Aster batangensis Aster batangensis 139 140 Inflasaponins I-V Glycyrrh iza injla t a 165 166 Astersaponin G Aster tataricus 141 167 Asteryunnanosides A and B Asteryunnanosides F and G Asteryunnanoside H Aster yunnanensis Aster yunnanensis Aster yunnanensis 142 143 144 Lonicerosides A and B Lupinosides PA,-PA Lonicera japonica Lupinus polyphyllus x L.arboreus 168 169 Barringtosides A-C Bellidioside A Barringtonia acutangula Bellum bellidioides 145 146 Malonylbuddlejasaponin IV Masonosides A-C Bupleurum fruticosum Crocosmia masoniorum 170 171 Besysaponins C, and C, Butyrosides C and D Calliandra saponins B C D Bellis sylvestris Madhuca butyracea Calliandra anomala 147 148 149 Medicago saponins P and P Ranuncosides I-VI Rubicunoside A Medicago polymorpha Hydrocotyle ranunculoides Silene rubicunda 172 173 174 Camelliasaponins B, B, C, Castaralesides F-H Cephalaria saponin A Chromosaponin I Clinoposaponins IX-XI and F and C Camellia japonica Castanospermum australe Cephalaria transsylvanicu Pisum sativus Clinopodium chinense var 150 151 152 153 154 Sideroxyloside A Sitakisosides I-V Solidagosaponins XXI-XXIX Songarosaponin D Soyasaponin aa Stachyssaponins I-VIII Tarasaponins 1-111 Siberoxylon cubense Stephenotis lutch uensis Solidago virga-aurea Verbascum songaricum Phaseolus coccineus Stachys riederi Aralia elata 175 176 177 178 179 180 181 Desacylmasonosides 4 and 5 parv gorum Crocosma masoniorum 155 Tarasaponins III-VII Thalicoside D Aralia elata Thalictrum minus 182 183 Dianchinenosides C and D Dianchinenosides E-H Dotorioside I Dulcin Eclalbasaponins I-VI Dianthus chinensis Dianthus chinensis Quercus acutissima Pithecellohium duke Eclipta alba 156 157 158 159 160 Thalictosides VI-VIII Transsylvanoside A Transsylvanoside B Yunnanglysaponins A and B Yuzhizioside IV Thalictrum spp.Cephalaria transsylvanica Cephalaria transsylvanica Glycyrrhiza yunnanesis Akebia trifoliata var. australis 42 184 185 186 187 Elatosides E and F Aralia elata 161 The following plant sources have been reported to contain unnamed saponins of known oleanane genins Alalia decaisnenana,ls8 Camellia sinensis var. sinensis,lsg Clematis koreana. var . um b rosa Fagonia cret ica Gypsophila capil- la~is,”~ Melanthera scandens,lg3 Myrsine pell~cida,’~~ Nothopanax da vidii 95 Oplopanax elatus ’O5 Phy tolacca dode- candra,Is6 Potentilla tormentilla,lg7 Ruta g~aveolens,’~~ Sapindus saponari~,’~~ SchejYera lucantha,lo6 Symphytum oficinaIe200 and Ximenia americana.201 The maprounic acid derivatives (186) and (187) have been found in Maprounea africana.202 Trichosanthes kirilowii is the R’. .. (187)R’ =H; R2=OH source of three new multifloranes 3-epikaounidiol (1 88) 3-epibryonol(l89) and 3a,29-dihydroxymultiflor-9(1l)-en-7-one (190).203 The 2-methylbutanoyl ester of glut-5-en-3a-01 (191) has been found in Euphorbia cyparis~ias.~~ XOH HO” Carthagenol from Cuphea carthagensis is friedel-7-en-3/3-01 (192).204 The structure of 11/3-hydroxyfriedel-l-en-3-one (193) from Phyllanthus flexuosus has been confirmed by X-ray NATURAL PRODUCT REPORTS 1996 analysis.2o5 Holoptelins A (194) and B (195) are fatty acid esters of friedelan-3P-01 from Holoptelea integrifolia.*06 Acan- thothamnus aphylus has been shown to contain 2m-hydroxypolpulnonic acid (196) friedela-2,4(23)-dien-29-oic (194) n=14 (195)#=16 acid (1 97) and the 29-norfriedelane (198).207 Magellanin (199) is a norfriedelane dimer from Maytenus magellanica.208 0 NATURAL PRODUCT REPORTS 1996-5.D.CONNOLLY AND R. A. HILL The norfriedelane 6-oxotingenol(200) has been isolated from rubra is urs- 12-ene-3P,30-diol (207).215Other new ursanes in- Maytenus ilicifolia and the corresponding methyl ether (201) clude 2a,3a,24-trihydroxyurs- 1 l-en-28,13P-olide (208) and the from M. chuchuhuasca together with the 22P,23-dihydroxy (E)-coumaroyl ester of 2a,3a,24-trihydroxyurs- 12-en-28-oic derivative (202)and 6-oxopristimerol (203).209 The structure of 3-0-methyl-6-oxotingenol (201) was confirmed by X-ray (OH structure analysis.Salaciquinone (204) is a dinorfriedelane \j\ HO@ R' 0 R2 0 (200) R' = R3=H; R2=Me (201) R' = R2 = Me; R3 = H (202)R' = Me; R2 = CH20H; R3 = OH acid (209) from Actinidiapolygama callus tissue,216 la,2a,3P,24- xmMe tetrahydroxyurs-12-en-28-oicacid (210) from Gentiunu tibe- tical2*and the esters (2 11)-(214) of 2a,3P-dihydroxyurs-l2-en-HO HO@ II '0 (203) from Sulacia reticuluta.210 Assignment of the 13C NMR of salaspermic acid and revision of the assignments for celastro1,211 dispermoquinone and isoguesterin210 have been reported.Further details of the synthesis of rhoxburghonic acid from putranjivadione have been published.212 7 The Ursane Group The 28-norursane (205) has been found in Shorea rob~sta.~~~ The unusually named pleuchioside from Pleuchea lunceolutu is ursane-3a 19~,20P-triol (206)*14 and rubrinol from Plumeria AcO@ HO.. R'OY (214) R' = H; R2 = OMe 28-0ic acid from Leptospermum scoporium.*17 The structures of the known euscaphic218 and rob~ric~~~ have been acids confirmed by X-ray analyses. Pinfaensic acid (215) is the genin of pinfaensin from Rubus pinfaensis.220 Gonganosides A-G are ursane saponins from Bhesa paniculata.221. 222 Gonganoside G has the new genin 27-oxoursolic acid (21 6). Scheffursosides B-F from Scheflera octophylla include the new genin 2a,3p- dihydroxy-23-oxours- 12-en-28-oic acid (2 1 ,).I2' Other new ursane saponins include dotorioside I1 from Quercus acut- and i.~sima,'~*one from Mimusops he~andra,~~~ two from Potentilla t~rrnentilla.~~' Rhoiptelenol (2 18) is a friedoursane from Ficus thunbergii.224 8 The Hopane Group Four new 3P-methylhopanoids (2 19)-(222) have been isolated from Acetobacter europeus.225 Incorporation studies with (219) R = OH (220) R=Me (221) R = Me; 11,12-dihydro (222) R = Me; extra Me in ring A [methyl-2H3]methionine indicated that the 3 1-methyl group of the hopanoids retained all three deuterium atoms.Trinor- hopane (223) has been identified in Dryopteris crassirhizoma and Gleichenia japonica.226 Other new hopanes include 17a,29- epoxyhopane (224) and hopan-29,17a-olide (225) from Cyathea ~pinulosa~~' and methyl 22-hydroxyhopan-29-oate (226) hop- 20(29)-en-20-01(227) and hop-20(30)-en-29-oic acid (228) from (224) R = H2 (225)R =O (226) (227) R' = Me; R2= OH (228) R'=COOH; R2=H NATURAL PRODUCT REPORTS 1996 the liverwort Fossombronica alaskana. 28 3a-H yd roxymore t- 22(29)-en-24-oic acid (229) is a constituent of Ficus th~nbergii.~*~ HO'* ; COOH The norhopane 19a-hydroxyadiantone (230) and fern-9( 1 1)-en-25-oic acid (231) have been isolated from Adiantum edgworthii2" and 4(23)-filicen-3a-o1 (232) and 3-filicen-2-one (233) from Cyathea spinulosa. 227 Rubiarbonone B from Rubia yunnanensis is 7p 19a,28-trihydroxyarbor-9(1l)-en-3-one (234).230 &--( @-..{ 0 OH 0 OH Treatment of hop- 17(21)-ene or hop-22(29)-ene with mont- morillonite clay produced the rearranged hopane (235) together with its As and isomers and a small quantity of fernenes.The rearranged hopanes have also been found in recent The lH and I3CNMR data of a series of hopanes and migrated hopanes have been published.232* 233 ,aH -H (235) NATURAL PRODUCT REPORTS 1996-5.D. CONNOLLY AND R. A. HILL 165 9 Miscellaneous Compounds Full details of the isolation of sodwanones A-C from Axinella weltneri together with the new sodwanones D (236) E (237) and F (238) have been Eight raspacionin ; HO ‘* OH (248)R = OC(CH2)7CH=CH(CH2)3CH3 (24)R = OC(CH2)1&H3 (250)R = OC(CH2)&H=CH(CH2)3CH3 (251)R = oC(CH&CH=CHCH&H=CH(CH2)4CH3 (252)R = OC(CH2)14CH3 (253)R = OC(CH2)gCH=CH(CH2)5CH (254)R = OC(CH2)11CH=CH(CH2)&H3 (255)R = OC(CH2)1&H3 0 derivatives (239)-(246) have been found in Raspaciuna acu- leata.235Stellettin A (247) is an isomalabaricane from Stelletta ten~is.~~~ Iris tectorum is the source of a range of esters OMe (2%) Bacchar-12,24-dien-3p-o1(257) has been isolated from Glycine max.239 Hosenkosides A-E,240 F-K241 and L-0242are go$ baccharane saponins from Impatiens balsamina including the new genins hosenkols C (258) and D (259).** OAc .I (239) (241)R’ = R3 = Ac; R3 = H HOfi (257) HOqljJ3-X . *’ OAc (242)R’ = H; R2 = AC OR’ (243)R‘ = R2 = H (245)R’ = Ac; R2 = H ‘-OH (244)R’ =Ac; R2=H (246)R‘ = H; R2 = AC (258) R=OH (259)R=H Gamrnacerane-3&,2 Ip-diol (260) and the corresponding 2 1-0 ketone (261) and 3,21-diketone*(262) have been found in Abies rnarie~ii.~~~ Picea jezoensis is the source of 2 lp-hydroxyserrat- 14-en-3-one (263)244 and its 21-methyl ether (264) and 21a- methoxyserrat- 13-en-3-one (265).245 I 0 (247) &R2 o&R \ R’ iristectorenes A (248) B (249) C (250) D (251) E (252) F (253) G (254)237 and H (255) together with a related series of (260)R‘ = a-0HJ-k R2 = B-OH,H (263)R=P-OH esters the iristectorenones A-H such as iristectorenone A (261)R‘ = a-OH,H; R2 = 0 (264)R=B-OMe (256),that are Diels-Alder adducts with belam~andaquinone.~~~ (262)R’ = R2 = 0 (265)R = a-OMe;AI3 166 10 References 1 S.B. 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Zhang and B. Yao J. Chin. Pharm. Sci. 1994 3 1 (Chem. Abstr. 1995 122 76495~). 187 S. C. Ma D. C. Chen and S. J. Zhao Yaoxue Xuebao 1994 29 285 (Chem. Abstr. 1994 121 175 1632). 188 X. Zeng Y. Zhou and Z. Fang Zhongguo Zhongyao Zashi 1994 19 550 (Chem. Abstr. 1995 122 101 556d). 189 Y. M. Sagesaka T. Uemura N. Watanabe K. Sakata and J. Uzawa Biosci. Biotech. Biochem. 1994 58 2036. 190 W.-K. Whang Arch. Pharmacol. Res. 1994 17 5. 191 F. R. Melek S. M. Abdel-Khalik T. Miyase and M. Y. Haggag Fitoterapia 1994 65 363. 192 M. H. A. Elgamal H. S. M. Soliman M. S. Karawya and H. Duddeck Nut. Prod. Lett. 1994 4 217. 193 A. Penders and C. Delaude Phytochemistry 1994 37 821. 194 C. Lavaud G. Massiot J.B. Barrera C. Moretti and L. Le Men- Olivier Phytochemistry 1994 37 1671. 195 S.-S. Yu Z.-Y. Xiao P. Cai T.-Y. Jiang and J. K. Snyder Tetrahedron 1994 50 11 601. 196 S. T. Thiilborg S. B. Christensen C. Cornett C. E. Olsen and E. Lemmich Phytochemistry 1994 36 753. 197 A. R. Bilia E. Palme S. Catalano G. Flamini and I. Morelli J. Nat. Prod. 1994 57 333. 198 S. K. Srivastava and S. D. Srivastava Fitoterapia 1994 65 301. 199 T. L. G. Lemos M. P. Sousa A. L. Mendes and R. Braz-Filho Fitoterapia 1994 65 557. 200 M. Noorwala F. V. Mohammad V. U. Ahmad and B. Sener Phytochemistry 1994 36 439. NATURAL PRODUCT REPORTS 1996 201 M. D’Agostino G. Biagi F. de Simone and C. Pizza Fitoterapia, 1994 65 59. 202 T. Pengsuparp L. Cai H. H.S. Fong A. D. Kinghorn J. M. Pezzuto M. C. Wani and M. E. Wall J. Nut. Prod. 1994 57 415. 203 T. Akihisa K. Yasukawa Y. Kimura M. Takido W. C. M. C. Kokke and T. Twamura Chem. Pharm. Bull. 1994,42 1101. 204 A. G. Gonzalez E. Valencia T. S. Exposito J. B. Barrera and M. P. Gupta Planta Med. 1994 60,592. 205 R. Tanaka Y. In T. Ishida and S. Matsunaga J. Nut. Prod. 1994 57 1523. 206 D. N. Mondal B. R. Barik A. K. Dey A. Patra and A. B. Kundu Indian Drugs 1994 31 69 (Chem. Abstr. 1994 121 5164h). 207 R. Estrada J. Cardenas B. Esquivel and L. Rodriguez-Hahn Phytochemistry 1994 36,747. 208 A. G. Gonzalez A. Crespo A. G. Ravelo and 0.M. Munoz Nar. Prod. Lett. 1994 4 165. 209 0. Shirota H. Morita K. Takeya H. Itokawa and Y. Iitka J. Nut.Prod. 1994 57 1657. 210 Y. Tezuka T. Kikuchi B. Dhanabalasingham V. Karunaratne and A. A. L. Gunatilaka J. Nut. Prod. 1994 57 270. 211 0. Ngassapa D. D. Soejarto J. M. Pezzuto and N. R. Farnsworth J. Nut. Prod. 1994 57 1. 212 S. K. Ghosh S. K. Datta and S. Das Indian J. Chem. Sect. B 1994 33 370. 213 R. K. Hota and M. Bapuji Phytochemistry 1994 35 1073. 214 M. S. Alam N. Chopra M. Ali M. Niwa and T. Sakae Phytochemistry 1994 37 521. 215 N. Akhtar A. Malik S. N. Ali and S. U. Kazmi Fitoterapia 1994 65 162. 216 Y. Sashida K. Ogawa T. Yamanouchi H. Tanaka Y. Shoyama and I. Nishioka Phytochernistry 1994 35 377. 217 H. Haberlein and K.-P. Tschiersch Phytochemistry 1994 35 765. 218 P. J. Cox D. G. Durham X. Liu and R. M. E. Richards J.Chem. Res. (S).,1994 122. 219 T. T. Jong and C.-T. 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Tanaka R. Tsuboi and S. Matsunaga Phytochemistry 1994 Arihara Chem. Pharm. Bull. 1994 42 1422. 37 209. 242 N. Shoji A. Umeyama K. Yoshikawa M.Nagai and S. Arihara 245 R. Tanaka C. Mun Y. Usami and S. Matsunaga Phytochemistry Phytochemistry 1994 37 1437. 1994 35 1517.

ISSN:0265-0568    

DOI:10.1039/NP9961300151

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Amaryllidaceae and Sceletiurn Alkaloids John R. Lewis Department of Chemistry University of Aberdeen Meston Walk Aberdeen AB9 2UE UK Reviewing the literature published in 1994 (Continuing the coverage of literature in Natural Product Reports 1995 Vol. 12 p. 339) 1 Introduction R3 R4 2 Occurrence and Structural Studies 1 3 Synthetic Studies 4 References 1 Introduction In this annual review five new alkaloids have been reported as (-)-galanthamine R' = lone pair; R2 = R5 = Me; R3 = OH; R4 = H well as known alkaloids that have been found in new sources. (-)-N(chloromethy1)galanthaminium chloride R' = R5 = Me; R2 = CH2CI; Table 1 lists those alkaloids that are reported upon in this R3=OH; R4=H review. Galanathamine (1) has been prominent in the popular (-)-galanthamine N-oxide R' = 0; R2 = R5 = Me; R3 = OH; R4 = H and general scientific press because of its purported usefulness lycoramine R' = lone pair; R2 = R5 = Me R3 = OH; R4 = H; ab sat.in healing Alzheimer's disease presumably due to its anti- sanguinine R' = lone pair; R2 = Me; R3 = OH; R4= R5 = H cholinesterase and muscarinic activity.' It has also been OdemethyllycorarnineR' = lone pair; R2 = Me; R3 = OH;R4= R5= H; patented for use in the treatment of nicotine dependence. If ab sat. it is extracted with methylene chloride or crystallised from epinorgalanthamine R' = lone pair; R2 = R3 = H; R4 = OH; R5 = Me norgalanthamine R' = lone pair R2 = R4= H; R3 = OH; R5 = Me the same solvent it forms a quaternary salt. The structure and absolute configuration of (-)-N-(chloromethy1)-epinorlycoramine R' = lone pair; R2 = R3 = H; R4 = OH R5 = Me; galanthaminium chloride (2) which is formed has been ab sat.This study emphasises nOrtyCOramine R' = lone pair; R2 = R4 = H; R3 = OH; R5 = Me; ab st. determined by X-ray ~rystallography.~ the care that needs to be taken when choosing a solvent to extract plant material. ether/water system modified by addition of trimethylamine A zone refining partition coefficient technique4 has been (5-10mM) to the organic phase and hydrochloric acid developed to separate alkaloids present in a crude extract of (5-10mM) to the aqueous phase it was possible to separate Crinurn rnoorei. Using an equilibrated methyl tert-butyl crinine (3) powelline (4)and crinamidine (5) in a 3 g extract. Table 1 The isolation of Amaryllidaceae and Sceletium alkaloids Species Alkaloid (Structure) Ref.Species Alkaloid (Structure) Ref. Brunsvigia josephinae 3-O-Acetylhamayne (6) 6 Sanguinine (29) Hamayne (7) Lycorine (13) Ambelline (8) Crinamine (9) O-Demethyllycoramine (30) 1 -Palmitoyl-2-lineoyl- Crinum asiaticum var. sinicum (bulbs) Sternbergine (10) Josephinine (1 1)* Crinisin (12)* Lycorine (1 3) 7 phosphatidyl-ethanolamine (31) 1-Palmitoyl-2-lineoyl-phosphatidyl- Crinum moorei Haemanthus albijlos Hippeastrum hybrids (bulbs) (bulbs) Lycoris incarnata (flowers) Powelline (4) Crinine (3) Crinine (3) Powelline (4) Crinamidine (5) Albiflomanthine (14)* 1l-Hydroxyvittatine (15) Vittatine (16) Montanine (17) Pancracine (1 8) Lycorine (1 3) Tazet tine (19) Haemanthamine (20) Hippeastrine (21) Incartine (22) Galanthine (23) Narcissidine (24) Galanthamine (1) Unigiminorine (25) Unigiminorine N-oxide (26) Galanthamine N-oxide (27) Lycoramine (28) 4 8 9 10 Narcissus leonensis (fresh whole plant) Narcissus prim igen ius Narcissus tazetta (whole plant) Sternbergia clusiani (bulbs) * New alkaloids methanol sodium salt (32) Epinorgalanthamine (39)* Norgalan t hamine (40) Epinorlycoramine (4 1)* Norlycoramine (42) Lycorine (13) Homolycorine (33) 8- O-Demethyl- homolycorine (34) Haemanthamine (20) 8-O-Demethyl-maritidine (35) 9-O-Demethyl-homolycorine (36) Galanthamine (1) Haemanthamine (20) Haemanthidine (37) 1l-Hydroxyvittatine (15) Crinine (3) Isotazettine (3 8) Lycorine (1 3) 14 11 12 13 (3) crinine R' = R2 = R3 = R4 = H (4) powelline R' = Me; R2 = R4 = H; R3 = OMe (5) crinamidine R' = R2 = R4 = H; R3 = OMe; ab = j3-epoxide (9) ambelline R' = Me; R2 = a-OH; R3 = R4 = H (37) haemanthidine R' = Me; R2 = a-OH; R3 = H; R4= OH The antiviral activity found in an extract of the bulbs of Haemanthus albiflos has been reinvestigated and it is confirmed that the extract does inhibit viral DNA synthe~is.~ 2 Occurrence and Structural Studies The bulbs of Brunsvigia josephinae contain six alkaloids,6 3-0-acetylhamayne (6) hamayne (7) crinamine (8) ambelline (9) sternbergine (10) and a new alkaloid josephinine (1 1).Crinsin (12) is a new alkaloid found in the bulbs of Crinium asiaticum var. sinicum;' it is accompanied by lycorine (13) powelline (4) and crinine (3).3-Qacetylhamayne R' = a-OCOMe; R2 = R3 = H hamayne R' = a-OH; R2 = R3 = H crinamine R' = a-OMe; R2 = OH; R3 = H albiflomanthine R' = p-OMe; R2 = R3 = OH 11 -hydroxyvittatine R' = POH; R2 = OH; R3 = H vittatine R' = P-OH; R2 = R3 = H haemanthamine R' = B-OMe; R2 = OH; R3 = H 0133 sternbergine R' = Me; R2 = H; R3 = COMe lycorine R'R2 = CH2; R3 = H galanthine R' = R2 = R3 = Me OCOMe (11) josephinine ?" *'OH Ho-9 I OMe (12) crinisin NATURAL PRODUCT REPORTS. 1996 As reported (loc. cit.) the total alkaloidal extract of this plant possesses antiviral a~tivity.~ Bulbs of Hippeastrum hybridsg have been shown to contain 1 1-hydroxyvittatine (1 5). Hitherto this alkaloid had only been found in plants belonging to the genus Sternbergi~.'~In addition vittatine (16) montanine (17) pancracine (18) lycorine (1 3) tazettine (19) haemanthamine (20) and hippe- astrine (21) were isolated.A comprehensive NMR study of these alkaloids involving 2D techniques such as HOHAHA ROESY and HMBC for lH and 13C assignments enabled structural elucidation to be facilitated. ,OR (17) montanine R = Me (18) pancracine R = H OMe I A' (19) tazettine R' = H; R2 = OH (38) isotazettine (pretazettine) R' = OH; R2 = H Rlo$..oH R20 0 hippeastrine R'R2 = CH2 homolycorine R' = R2 = Me 8-Odemethylhomolyconne R' = H; R2 = Me 9-Qdemethylhomolyconne R' = Me; R2 = H Incartine (22) a supposed biosynthetic intermediate between galanthine (23) and narcissidine (24) has been obtained from the flowers of Lycoris incarnata.1° Also present were galan- thamine (I) ungiminorine (25) ungiminorine N-oxide (26) galanthamine N-oxide (27) lycoramine (28) sanguinine (29) (22) incartine OMe HO..A..OH A new crinan alkaloid called albiflomanthine has been (24) narcissidine R' = lone pair; R2 = R3 = Me isolated from the bulbs of Haemanthus albzjlos.8It possesses the (25) ungiminorine R' = lone pair; R2R3 = CHz unusual feature of having an oxygen substituent at C-4 (14).(26) ungiminorine Noxide R' = 0; R2R3 = CH2 NATURAL PRODUCT REPORTS 1996-J. R. LEWIS I73 CH2-O-CO(CH2)1 6Me lycorine (13) 0-demethyllycoramine (30) as well as l-palmitoyl- F;H-0-CO(CH2)7CH= CHCH2CH =CH(CH2)7Me 2-linoleoylphosphatidylethanolamine(31) and 1-palmitoyl-2-lineoylphosphatidylmethanol sodium salt (32).CH2- O-P0&H2CH2he3 Narcissus primigenius which is a new taxon belonging to the (31) 1-palmitoyl-2-linoleoylphosphatdylethanolamine Pseudonarcissus DC section contains four alkaloids,ll namely homolycorine (33) 8-0-demethylhomolycorine (34) haem- anthamine (20) and 8-0-demethylmaritidine (35). F;H~-O-CO(CH~)I6Me Narcissus tazetta grown in Egypt contains 9-0-demethyl- CH-0-C0(CH2),CH=CHCH2CH=CH(CH2)+e homolycorine (36). l2 CH2-0-PO(0Me)ONa The bulbs of Sternbergia clusiani contain seven alkaloids,13 including galanthamine (I) haemanthamine (20) haem-(32) 1-palmitoyl-2-lineoylphosphatidylmethanoI sodium salt anthidine (37) 11-hydroxyvittatine (15) crinine (3) and iso- tazettine (38) while the most abundant alkaloid present was lycorine (13).,OMe Narcissus leonensis fresh whole plants contain the new alkaloid epinorgalanthamine (39) accompanied by norgalanth- amine (40) epinorlycoramine (41) lycorine (13) and b9. norlycoramine (42). All these compounds were characterised by 6ontPoR ' -* N NMR (43) coccinine R = H (44) Oacetylcoccinine R = Ac 3 Synthetic Studies A review of the total synthesis of montanine type alkaloids -OH namely ( _+)-montanine (17) ( ))-coccinine (43) ( &)-O-acetyl-coccinine (44) ( f)-pancracine (1 8) and ( f)-brunsvigine (45) includes techniques such as hydroboration-oxidation of the exo-methylene group cyclisation of tosylamide alcohols with 'Vitrimide ' and steroselective selenation of 01efins.l~ (45) Brungsvigine (-)-Mesembranol (62) the alkaloid found in Sceletium species has been synthesised (Scheme 1).16 Starting from D-Ph..RO" "me MOMO" "OMe OR OMOM OMOM OMOM Me0 OMe I' HO 0 HO.. viii vi 4- MOMO'. OMOM OMOM OMOM OMe OMe OMe \ / OMe 6"' R-8xv %iR $OM. xii __t __t OMOM OMOM A Me OMOM (56) R = CHO CO2Et (61) R=MOM MOMO'. 8.RO'. Q-xiii c(58) R = xi C xvi C (55) (57) R = H (59) R = CHO (62) (-)-mesembranol R = H xiv (60) R = CH2NHMe Reagents i chloromethyl methyl ether PraNEt CH,Cl, reflux 18 h; ii NBS BaCO, CCI, 1,1,2,2-tetrachloroethane,reflux 20 h; iii DBU toluene 75 "C 20 h; iv Hg (OCOCF,) (0.5 mol%) acetone/H,O (2:l) rt 72 h; v MsC1 Et,N CH,Cl, rt 30 min; vi 3,4- dimethoxyphenyllithium Et,O -78 "C then MeONa-MeOH ; vii H, Pd(OH), EtOAc; viii 1,l'-thiocarbonyldiimidazole,acetone reflux 48 h; ix P(OMe), reflu 72 h ;x and xi 30 % aq.HCO,H 30 "C 72 h then K,CO, MeOH rt ;xii triethyl orthoacetate 2 % propionic acid v/v molecular sieves 3 A 135 OC 48 h; xiii DIBAL toluene -78 "C; xiv MeNH (30% MeOH/H,O) NaBH,CN MeOH rt 24 h; xv Hg (OAc), THF rt then NaBH, THF aq. NaOH rt; xvi 6 mol dm- HCl/THF (1 :2 v/v) rt Scheme 1 NATURAL PRODUCT REPORTS 1996 Me0 \ Me0 OMe (66) (67) (68)vasconine (69) assoanine R=2H (70) oxoassoanine R = 0 OMe OMe (65) Reagents i Indoline (63) N,N,N',N'-tetramethylethylenediamine N, Et,O -40 "C then Bu'Li cyclohexane -40 to -50 "C then CuI-P(OEt) complex stir -45 "C 30 min then aldimine (64) warm to rt 1 h;ii 1 M HCl THF reflux 30 min; iii HCl (g) CHCl, rt 15 min; ivy EtOH NaBH, rt 30 min; v H,O N, NaOH KMnO, CH,Cl, 20 "C stir Scheme 2 glucose the established Ferrier rearrangement produced methyl-[4.6.0]-benzylidene-ol-~-altopyranoside (46) which was protected as its bismethoxymethyl ether (47) before being transformed into bromo-ether (48) by treatment with NBS in carbon tetrachloride containing BaCO,.Dehydrobrqmination gave exomethylene (49) which upon Ferrier carbocyclisation produced cyclohexanone (50). This without purification was converted into enone (5 1). Reaction with 3,4-dimethoxy-phenyllithium at -78 "C gave enol (52) which was reduced catalytically to (53) prior to being converted with the thiocarbonate (54) ; elimination then giving alkene (55).After several attempts formic acid treatment and deprotection gave a number of products all of which were hydrolysed and separated to give mostly alcohol (57). Claisen rearrangement of (57) with triethyl orthoacetaote acidified with a trace of propionic acid in the presence of 3A molecular sieves gave ester (58) which was converted into N-methylamine derivative (60). Intramolecular cyclisation with mercuric acetate gave the saturated protected mesembranol (6 1) which upon depro- tection gave the natural product (-)-mesembranol (62). See Scheme 1.16 Pyrrolophenanthridine alkaloids vasconine (68) assoanine (69) and oxoassoanine (70) have been concisely synthesised using the Ullmann reaction under Ziegler conditions (room temperature) as shown in Scheme 2.Thus N-Boc-indoline (63) reacted with sec-butyllithium followed by the CuI-P(OE) complex to give copper complex (64). This condensed with iodobenzaldimine (65) to give aldimine (66) which upon hydrolysis gave its aldehyde (67). Intramolecular cyclisation was achieved by removal of the pyrrolidine Boc protecting group creating the quaternary salt vasconine (68). Sodium borohydride reduction gave assoanine (69). Alternatively oxidation of (68) with alkaline permanganate gave oxo-assoanine (70). See Scheme 2.l' A synthesis of the 1,3-dioxolo[4.5-j]phenanthridin-6-[5H]-one ring system by a convergent route involves first a Suzuki OH w 6+NH RO (71) narciclasine R = OH (73) lycoriicidine R =ti Y -I II OH 0 (72) pancratistatin coupling reaction followed by a Bischler-Napieralski cyclisation.As yields in these two reactions are excellent the method (Scheme 3) has potential use in making important members of this group such as narciclasine (71) pancratistatin (72) and lycoricidine (73). (74) Br Q $JH C02Me (75) 0 (79) Nmethylcrinasiadine R = Me (80) trisphaeridine R = H Pd 0 CaMe (76) ii t R (77) R=CI (78) crinasiadine R = H iii Reagents i Pd(PPh,), EtOH bz Na,CO, N, reflux 8 h; ii POCI, sealed tube 155 "C 12 h; iii 6 M HCl THF rt 7 d; iv Me,O+ BF, CH,Cl, reflux 12 h then NaOH (2 M) rt 18 h; v KOH (2 mole) 10% PdC toluene/MeOH (6 I) H, 18 "C 24 h Scheme 3 In this paper crinasiadine (78) N-methylcrinasiadine (79) and trisphaeridine (80) are synthesised (Scheme ,).la Firstly the boronic acid (74) was condensed with bromocarbonate (75) in the presence of the PdO reagent to give biaryl (76) in high yield (90 YO).This carbamate (76) underwent cyclisation with POCI at 160 "C to give the chlorophenanthridine (77) which upon hydrolysis gave ( f)-crinasiadine (78). N-Methylation to (79) could be achieved using the chlorophenanthridine (77) which with methyloxonium tetrafluoroborate followed by in situ hydrolysis gave ( & )-N-methylcrinasiadine (79). Reduction of the chloroimine (77) gave ( )-trisphaeridine (80).NATURAL PRODUCT REPORTS 1996-5. R. LEWIS The same group have further developed the method to synthesise both enantiomeric forms of this tricyclic skeleton (Scheme 4).19 Racemic isocyanate (82) prepared from the dibromocarbene adduct (81) and silver isocyanate gave a mixture of R-and S-enantiomers (83) which on Suzuki coupling gave the aryl L-menthyl carbamates (84) and (85) separated by crystallisation and chromatography. Both compounds under- went cyclisation to the respective isoquinoltones (86) and (87) respectively. Chirality was confirmed by X-ray measurements on one of the carbamate~.'~ 0 (82) (83)R' = L-menthyl iii B(oH)2 I t fi (Ofl HNK 0 .OR' (O@ 0 0 0 (86)R-isomer (85) Sisomer ~ (OG 0 0 (87) S-isomer Reagents :i AgNO (1.2 eq.) 1 ,Cdioxane 100 "C 4 h; ii (-)-Menthol (5 eq.) 1,4-dioxane 100 "C 24 h; iii Pd(PPh,) (3 mol'h) 2 mol dm- aq.Na CO, EtOH 80 "C,12 h; iv POCl, 80 "C (sealed tube) 7 h then 0.2 mol dm- HCl in THF/H,O (10.1) 18 "C,30 min Scheme 4 0 (911 A further application of this synthetic procedure20 has been to synthesise the natural product 5,6-dihydrobicolorine (88). The synthetic product obtained differed considerably (spectro- scopic properties) from that reported for the natural product. Further studies on the synthetic material indicated its in- stability; heating in the presence of air produced a ketone (79) i.e. N-methylcrinasiadine. On this evidence it is suggested that naturally occurring 5,6-dihydrobicolorine has the same structure as ismine (88).0 Characteristic of all galanthamine alkaloids e.g. narwedine (90) are their quaternary carbon centres the focal point to any synthetic scheme. Narwedine was originally created in 1962 by phenol oxidation in a 'biomimetic synthesis' albeit in 1.4% yield from norbelladine (89). A substantial improvement occurred in 1988 with a radical cyclisation process being achieved through the use of a palladium complex (91) which generated racemic narwedine (90) in 5 1YOyield.,' Reduction of (+)-narwedine (90) gave a mixture of (+)-galanthamine (1) and (+)-epigalanthamine (92) (Scheme 5). Since (-)-galanthamine (1) is the alkaloid with substantive pharmacological properties (anti-cholinesterase muscarinic and anti-nicotinic activity) its stereospecific synthesis is now a prime objective.To this end (+)-narwedine (90) has now been found to be asymmetrically transformed via a 'total resolution process ' into predominately one enantiomer by a crystallising procedure as shown in Scheme 6.22A saturated solution of (-t)-narwedine (90) in a solvent mixture (95% ethanol/5% triethylamine) at 80 "C was cooled to 68 "C and this super- saturated solution when seeded with either (-)-narwedine or (+)-narwedine gave a crystalline deposit of an enriched enantiomer (-84 %). The reason for this spontaneous res- olution can be explained by retro-Michael ring opening followed by ring closure at the quaternary centre. If this spontaneous resolution process was initiated by ( +)-galanthamine then (-)-narwedine was obtained; two cycles produce 9.02 g of (1) (?)-galanthamine (92) @)-epigalanthamine Reagents i MeSCH,Cl HMPA N, Na salt of (89) rt 0.5 h; ii lithium tetrachloropalladate MeOH PrkNH -78 "C; iii thallic trifluoroacetate (2 eq.) CH,Cl,/TFA (2 l) -10 "C 1.5 h; iv LiAlH, THF 0 OC then reflux 12 h Scheme 5 NATURAL PRODUCT REPORTS 1996 0 0 0 (+)-na wed ine 85% - (-)-galanthamine75% NMe Me0 (-)-narwedineI L-sebctricie (90) (+)-riawedine (+)-narwedine OH '@NMe o@NMe Me0 (1) (-)-galanthamine (+)-galant hamine Scheme 6 optically pure (-)-narwedine from 10 g of the racemate and from this can be produced optically pure (-)-galanthamine (1) (Scheme 6).22 4 References A.B. Kosmacher I. M. Kosmacheva M. B. Yankhotova and V. I. Kuleshov Eksp. Klin. Farmakol. 1994 57 6; (Chem. Abstr. 1994 121 49906). J. A. Moormann PCT Int. Appl. WO 9416 708; (Chem. Abstr. 1994 121 172911). R. Matusch M. Kreh and U. Muller Helv. Chim. Acta 1994,77 161 1. Y. Ma Y. Ito E. Sokolsky and H. M. Fales J. Chromatogr. 1994 685 259. G. P. Husson P. H. Vilagines B. Sarretto and R. Vilagines Ann. Pharm. Fr. 1994 52 311; (Chem. Abstr. 1995 122 23285). F. Vildomat J. Bastida C. Codina W. E. Campbell and S. Mathee Phytochemistry 1994 35 809. R. J. Tang N. J. Bi and G. E. Ma Chim. Chem. Lett. 1994 5 855; (Chem. Abstr. 1995 122 128545). G. Bandouin F. Tillequin and M. Koch Heterocycles 1994 38 965; (Chem. Abstr. 1994 121 78324).C. Muegge B. Schablinski K. Obst and W. Dopke Pharmazie 1994 49 444 (Chem. Abstr. 1994 121 117459). 10 M. Kihara L. Xu K. Konishi K. Kida Y. Nagao S. Kobayashi and T. Shingu Chem. Pharm. Bull. 1994 42 289. 11 J. Bastida S. Bergonon F. Viladomat and C. Codina Planta Med. 1994 60 95; (Chem. Abstr. 1994 120 294172). 12 A. Evidente R. Lanzelta A. H. Abon-Donia M. E. Amer. F. F. Kassem and F. M. Harraz Arch. Pharmacol. 1994 327 595; (Chem. Abstr. 1994 121 200918). 13 S. Abdalla M. A. Zarga and S. Sabri Fitoterapia 1993 64 518 (Chem. Abstr. 1994 121 73379). 14 J. Bastida F. Viladomat S. Bergonon J. M. Fernandez C. Codina M. Rubiralta and J. C. Quiron Phytochemistry 1993 34 1656. 15 0.Hoshino and M. Ishizaki Yuki Gosei Kagaku Kyokaishi 1994 52 207; (Chem.Abstr. 1994 120 299027). 16 N. Chida. K. Sugihara and S. Ogawa J. Chem. SOC. Chem. Cornmun. 1994 901. 17 J. S. Parnes D. S. Carter L. J. Kurz and L. A. Flippin J. Org. Chem. 1994 59 3497. 18 M. G. Banwell and C. J. Cowden Aust. J. Chem. 1994,47,2235. 19 M. G. Banwell C. J. Cowden and M. F. MacKay J. Chem. Soc. Chem. Commun. 1994 61. 20 C. J. Cowden M. G. Banwell and I. C. S. Ho J. Nat. Prod. 1994 57 1746. 21 R. A. Holton M. P. Sibi and W. S. Murphy J. Am. Chem. Soc. 1988 110 314. 22 W.-C. Shieh and J. A. Carlson J. Org. Chem. 1994 59 5463.

ISSN:0265-0568    

DOI:10.1039/NP9961300171

出版商:RSC    

年代:1996

数据来源: RSC

摘要:

Hot off the Press Robert A. Hill' and Andrew R. Pitt2 'Department of Chemistry Glasgow University Glasgo w G 72 800,UK. E-mail bobh@chem.gla.ac.uk Department of Pure and Applied Chemistry Strathclyde University Thomas Graham Building 295 Cathedral Street Glasgow G 7 IXL UK. E-mail a.r.pitt@strath.ac.uk ~~ ~~ ~ -Reviewing the recent literature on natural products and bioorganic chemistry Nostocyclamide (1) is an interesting metabolite isolated from the dinitrogen-fixing cyanobacterium Nostoc 3 1 (F. Jiittner et al. J. Org. Chem. 1995 60 7891). Nostocylamide is apparently derived from a cyclic hexapeptide. However extensive modifications have occurred to produce two thiazoles and an oxazole as structural features. Dreschel has found the siderophore yersiniabactin (2) which contains two thiazoline rings and one thiazolidine ring in cultures of Yersinia enterocolitica (Liebigs Ann.Chem. 1995 1727). OA NH A new sesterterpenoid skeletal class has been found in suberitenone A (3) from the Antarctic sponge Suberites sp. (J. Shin et al. J. Org. Chem. 1995 60 7582). The authors have 0 (3) ?H HO2 named the new skeleton suberitane and postulate that cyclisa- tion to form ring C involves an exomethylene rather than the normal trisubstituted double bond in related skeletal classes. The structure of isoeudistomin U has been revised from (4) to (5) on the basis of a total synthesis using the Pictet-Spengler condensation of indole-3-carboxaldehyde with tryptamine followed by partial oxidation with DDQ (G.Massiot et al. J. Nat. Prod. 1995 58 1636). The novel thienocyclopentapyran xanthienopyran (6) has been found in the fruits of Xanthium pungens (Tetrahedron Lett. 1995 35 8985). Glabrescol(7) is a remarkable squalene-derived constituent of Spathelia glab- rescens that contains five tetrahydrofuran rings and probably arises from a meso-hexa-epoxide of squalene by a cascade of cyclisation steps (Reynolds et al. Tetrahedron Lett. 1995 36 9 137). The group of Singh has reported the isolation structure determination chemistry and biology of the actinoplanic acids A and B potent inhibitors of the ras farnesyl protein transferase a protein which is modified in many forms of cancer. Based on a C, polyketide the most potent form is actinoplanic acid B (8) (S.B. Singh et al. J. Org. Chem. 1995,60 7896). A new series of bicyclic lactones the plakortones (9) have been isolated C02H H R = Me Et (4) (9) ... 111 from the marine sponge Plakortis halichondrioides. The iso- lation was achieved using a bioassay for the activation of the cardiac SR-Ca' pumping ATPase which detects (9) at micromolar concentrations (A. D. Patil et al. Tetrahedron 1996 52 377). A brief but informative introduction to the importance of the carotenoids by J. A. Olsen and N. I. Krinsky appeared as a leader for a series of articles on the carotenoids (FASEB J. 1995 9 1547). The subsequent paper (G. Britton ibid. 1551) outlines the structure and properties of the carotenoids in relation to their function.The variability and instability of plant cell suspension cultures create major problems for the efficient production of secondary metabolites. Schripsema and Verpoorte (J. Nat. Prod. 1995 58 1305) have developed techniques for growth character- isation of these cultures which should help in improved yields of metabolite production. An endophytic fungus (Taxomyces andreanae) has been isolated from the inner bark of Taxus brevifolia. This fungus has been shown to produce TaxoP de novo (Stierle et al. J. Nat. Prod. 1995,58 1315) which opens up the possibility of microbial taxol biosynthesis and production. A study of the biosynthesis of clerodanes by cultured cells of Heteroscyphys planus (liverwort) using 13Clabelled mevalonic acid has demonstrated that the diterpene and sesquiterpene sections of the clerodane are labelled to a different extent suggesting that as in higher plants the biosynthesis of the diterpene and sesquiterpene sections occurs at separate sites within the cell.The study also confirmed that a methyl migration is involved in the formation of the trans-clerodanes NATURAL PRODUCT REPORTS 1996 challenged the accepted mechanism for the concerted cyclisation of 2,3-oxidosqualene to lanosterol by lanosterol synthase from yeast. When 20-oxa-2,3-oxidosqualene(13) is treated with yeast lanosterol synthase a minor (3.4 "/o) tetracyclic product (14) is produced together with the expected cyclisation product (15). Corey argues that this is evidence for the intermediacy of discrete cations such as (16) in the cyclisation of 2,3-oxidosqualene.Hoshino has shown that the 10,15-diethyl analogue of 2,3-oxidosqualene forms monocyclic compounds such as (1 7) when treated with oxidosqualene-lanosterol cyclase (J. Chem. Soc. Chem. Commun. 1995 2401). The authors suggest that the ethyl groups prevent the squalene analogue from adopting the correct conformation on the cyclase. Interestingly achilleol A (18) from Artemisia odorata is probably formed by a defective oxidosqualene-lanosterol cyclase enzyme. *Y (K. Nabeta T. Ishikawa and H. Okuyama J. Chem. SOC. Perkin Trans. I 1995 3111). Nabeta has also studied the biosynthesis of the phytyl side-chain of chlorophyll a (10) in liverwort using labelled mevalonate and found that there is more label in the portion derived from farnesyl diphosphate (FPP) than in the terminal prenyl unit.However when labelled glycine is used the labelling in the phytyl side-chain is uniform (J. Chem. SOC.,Chem. Commun. 1995,2529). It is known that labelled glycine is converted into endogenous labelled mev- alonate within the chloroplasts. Hence the authors suggest that the phytyl unit is biosynthesised in two separate stages. Hao and Yeoman have shown that tobacco cell suspension cultures convert nicotine (1 1) into nornicotine (12) without racemisation (Phytochemistry 1996 41 477). This result suggests that demethylation of nicotine does not involve ring opening of the pyrollidine ring as has been proposed earlier.HO (17) R = Me (18) R = H RO11 FPP Portion (11) R=Me (12) R= H An outline of the problems and strategies for oligosaccharide synthesis has been published by Boons (Tetrahedron 1996,52 1095). This paper again shows the broad scope of chemistry needed in this area. Two 2-deo~y-2~2-difluoro glucosides (19) have been designed and synthesised by S. Withers and co- workers as mechanism based inhibitors of yeast a-glucosidase and human pancreatic a-amylase (J. Biol. Chem. 1995 270 26778). They trap the enzyme by the accumulation of a stable difluoroglycosyl-enzyme intermediate. /OH A second cma gene from Mycobacterium tuberculosis has been isolated and cloned whose product cyclopropanates a double bond in the mycolic acid membrane component of this pathogenic mycobacterium.It is postulated by the authors that the cyclopropanation may help to maintain the structural integrity of the cell wall complex in the hostile environment in which they exist (K. M. George et al. J. Biol.Chem. 1995,270 27 292). E. J. Corey et al. (J. Am. Chem. SOC.,1995,117 11 819) have NATURAL PRODUCT REPORTS 1996-HOT OFF THE PRESS (2R,3S)- or (2S,3R)-2-benzyl-3,4-epoxybutanoic acid is a purpose designed efficient fast acting pseudomechanism based inhibitor of carboxypeptidase A (Scheme 1). The activated zinc chelated epoxide is attacked by the carboxylate anion of Glu- 270 (S. S. Lee et al. J. Chem. SOC.,Perkin Trans. I 1995,2877). Amazingly high regioselectivity has been demonstrated in the hydrolysis of the diacetate of 2-alkylbut-2-ene- 1,4-diols using lipase AL (Meito) in the work of Itoh and co-workers (Tetrahedron Lett.1996 37 91). The acetate at C-1 is preferentially hydrolysed (Scheme 2). Scheme 1 1 AcOYOAC lipase w HOToAC R . R Scheme 2 The stereochemistry of the reversible conversion of iso- butyryl-CoA into n-butyryl-CoA catalysed by the B, dependent isobutyryl-CoA mutase has been studied using isobutyryl-CoA labelled with 13C in the prochiral methyl groups (J. A. Robinson et al. J. Am. Chem. SOC.,1995 117 11285) (Scheme 3). Gradient enhanced inverse-detected hetero- nuclear 'H-'"C NMR spectroscopy was used to monitor the turnover of the labelled isobutyryl-CoA directly in the NMR tube.The results show that there is a stereochemical preference for the carbonyl thioester to migrate to the pro-S methyl group of isobutyryl-CoA. However a migration also occurs at a slower rate to the pro-R methyl group. Golding and co-workers have proposed a new hypothesis for the mechanism of a number of B,,dependent mutases including the glutamate mutase from Clostridium cochlarium. ESR studies suggest the involvement of a transient fragmentation process and not the formation of an intermediate cyclopropyl species. The fragmentation of the radical generated by hydrogen abstraction from the substrate generates acrylate and another radical which can then recombine to give the mutated product (B. Beatrix et al. Angew. Chem. Int.Ed. Engl. 1995 34 2398). Me 0 Me*-4fscoA 0 Scheme 3 trans-2-tert-Butoxy-3-phenylcyclopro~ylmethane (20) is a useful hypersensitive radical probe that has been utilised by the group of Newcomb to study the mechanism of cytochrome P-450 hydroxylations (J. Am. Chem. SOC.,1995 117 12085). These studies have indicated that the reaction is a non-synchronous concerted process with the major product deriving from an unexpected cationic pathway as well as minor products from the radical pathway. The estimated radical lifetime is less than lOOfs which would mean that the radical is not a true intermediate but part of a transition state complex. Jones and co-workers (J. Am. Chem. SOC.,1995,117 12281) have shown that 15N NMR of 15N labelled oligodeoxy- nucleotides can be successfully used to probe the Hoogsteen hydrogen bonding in duplex and triplex structures.The development of a high yield route to doubly 15N labelled bases should help increase the information available by this technique (Jones J. Am. Chem. SOC.,1995 117 11669). Mueller and Pardi (J. Am. Chern. SOC.,1995,117 11 043) have used 2D 15N correlated NOESY experiments to obtain distance information for amino protons in nucleic acids. Three-dimensional solid state 15NNMR of uniformly 15N labelled proteins as reported by S. J. Opella and co-workers (J. Am. Chem. SOC.,1995 117 12348) promises to be an important technique in protein structure determination. Direct observation of an amino-acrylate-enzyme intermediate in the tryptophan synthase reaction (21) has been achieved using ~-[3-~~C]serine as the substrate and solid state NMR.The formation of the aminoacrylate can be directly observed on addition of the serine and a redistribution of the equilibrium towards the methyl ketoamine tautomer is observed on the addition of indolepropan-3-01 phosphate an inhibitor that binds directly to the a-subunit (L. M. McDowell et al. J. Am. Chem. SOC. 1995 117 12352). H,' 3CYc02H H The crystal structure of an aldehyde oxoreductase from Desulfuribrio gigas which appears to be a member of the xanthene oxidase class has been determined by the group of Huber. The enzyme is a homodimer and contains the molybdopterin cofactor and two Fe,S centres. This is the first time that the molybdopterin cofactor has been seen in atomic detail and is the first look at an enzyme of the xanthene oxidase class.(M. J. Ron50 et al. Science 1995,270 1170). An atomic model of the T4 endonuclease V (which catalyses the first step in pyrimidine dimer specific base excision) complexed to modified DNA containing a thymineodimer has been determined from the crystal structure to 2.75 A resolution. The DNA is uniquely kinked with a 60" inclination at the centre of the thymine dimer and the complementary adenine flipped out of the DNA into a pocket on the enzyme (Cell 1995 83 773). C. B. Post and W. J. Ray have re-examined the mathematical model of induced fit theory for two substrates where the chemical step is rate limiting. They have developed a new model which contrary to the original which suggests there should be NATURAL PRODUCT REPORTS 1996 no specificity indicates that if the conformational changes cyt c peroxidase H202 + 2 H+ e-]kqt (Ox') x (red.) persist in the transition state specificity can be observed (Biochemistry 1995 34 15881).This opens up the possibility that in evolutionary terms there may be a direct link between cyt c (red.) cyi c peroxidase 2H20 enzyme specificity and induced conformational changes. (ox.) By using direct electrochemical coupling of two components Scheme 4 of the biological electron transport chain cytochrome c peroxidase in solution and cytochrome c attached to a modified surface (Scheme 4) it is possible to directly monitor electron the electrospray ionisation mass spectrometry of oligo-transfer between the two proteins and hence study the molecular saccharides can be obtained by derivatisation with 4-amino- recognition between the enzymes (L. Jiang et al. Angew. benzoic acid 2-diethylaminoethyl ester (K. Yoshimoto et al. Chem. Int. Ed. Engl. 1995 34 2409). Improved sensitivity in Anal. Chem. 1995 67,4028).

ISSN:0265-0568    

DOI:10.1039/NP996130iiib

出版商:RSC    

年代:1996

数据来源: RSC