摘要:

Cyclopeptide alkaloids Dimitris C. Gournelif Gregory G. Laskarisb and Robert Verpoorte*9b "Aristotelian University of Thessaloniki Department of Pharmacy Laboratory of Pharmacognosy Thessaloniki 540 06 Greece 'Biotechnology Deyt Leiden Projectgroup Plant Cell Biotechnology Center for Bio-Pharmaceutical Sciences Division of Pharmacognosy Gorlaeus Laboratories 2300 RA Leiden The Netherlands Covering January 1985 to December 1995 Previous review The AZkaZoids ed. A. Brossi Academic Press New York 1985 vol. 26 pp. 299-306 1 Introduction 2 Classification 3 Structures of new compounds 4 Sources 5 Structure elucidation stereochemistry 6 Synthesis 7 Biological activity 7.1 Sedative activity 7.2 Antibacterial activity 7.3 Antifungal activity 8 Biosynthesis tissue culture 9 Conclusions 10 References 1 Introduction Cyclopeptide alkaloids are defined as basic compounds embodying an ansa structure in which a 10- or 12-membered peptide-type bridge spans the 1,3 or 1,4 positions of a benzene ring.' They are widely distributed among plants of the Rham- naceae family but their occurrence has also been confirmed in representatives of Asteraceae Celastraceae Euphorbiaceae Menispermaceae Pandaceae Rubiaceae Sterculiaceae and Urticaceae.The general structure of cyclopeptide alkaloids is designated in Fig. 1. 'N-R5 '& A '*-..--___.___--R4 -,'' A = basic terminal (end) amino acid B = P-hydroxy amino acid C = ring-bound amino acid D = hydroxystyrylamine unit Sometimes between the A and B unit an additional (intermediary) amino acid is present and is designated as E.Fig. 1 General structure of cyclopeptide alkaloids Although several reviews have been published covering 110 cyclopeptide alkaloids,'-' there are no recent reviews. In the present work we summarize this field for the period from Gournelis. Laskaris and Vemoorte CvcloDeDtide alkaloids 11 1985. Where appropriate data for compounds that were identified before 1985 but were not mentioned in the above reviews are included. Thus we will deal with 50 cyclopeptide alkaloids which include genuine cyclopeptide alkaloids (sensu stricto) some linear (open) peptide alkaloids as well as neutral compounds that do not present basic properties and are not considered to be alkaloids.Linear peptides and neutral compounds are closely related structurally (and biogenetically) with genuine cyclopeptide alkaloids and have been isolated from the same sources as cyclopeptide alkaloids. A striking exception are the celenamides that have been isolated from sponge^.^^'^ The linear peptides are considered to be the biogenetic precursors of the cyclic structures. 2 Classification Different methods of classification have been proposed in previous review articles. 1,2,4-6 In this review the compounds are presented in a way that copes with the plethora of structures that have been isolated. It was originally proposed by Joullie and Nutt6 and it comprises three gradings. (i) The cyclopeptide alkaloids sensu stricto (47 new compounds out of 15 1 in total) the linear peptide alkaloids (1 new compound out of 6 in total) and neutral compounds (2 new compounds out of 3 in total).(ii) The cyclopeptide alkaloids semu stricto are classified according to the size of the macrocycle 13- 14- or 15-membered rings. The 14-membered ring class has the most representatives. (iii) The 13- 14- or 15-membered ring com- pounds are further divided according to the number of their units 4 (having A B C and D units) and 5 (with A B C D and E units). Consequently the cyclopeptide alkaloids sensu stricto are subdivided in groups with the following annota- tions 4(13) 5(13) 4(14) 5(14) and 4(15). The 4(14) and 5(14) alkaloids are further subdivided according to the nature of the p-OH amino acid (B unit).The 4(13) 5 (13) and 4(15) alkaloids are uniform groups. The nomenclature is shown in Table I however there are some exceptions. In 4(14) com- pounds there is the group of pandamine type compounds (8 compounds in total) that contain a 2-alkoxy-2-(p-hydroxypheny1)ethylamine D unit instead of styrylamine. In 5(14) compounds hymenocardine contains valine as a B unit and a 2-alkoxy-2-(p-hydroxyphenyl)ethylamineD unit instead of styrylamine. The nomenclature of every group e.g. frangulanine type is based on the first representative that was isolated and has been kept unaltered in this review by using the trivial names. This kind of classification allows easy correlation or references to known compounds.In this sense the prefixes N-and 0-desmethyl- or N-and 0-methyl- were used. We would like to stress that several cyclopeptide alkaloids have been recoqded as separate compounds without mention or reference to previously isolated compounds possessing identical chemical structures. Some of the newly isolated cyclopeptide alkaloids must be identical with the older ones or be a stereoisomer. Therefore daechuine-S10 12 is 75 Table 1 Nomenclature of cyclopeptide alkaloids (the nature of the P-OH amino acid is in parentheses) Size of the macrocycle Number of units 13 atoms 14 atoms 15 atoms 4(13)-compounds 4( 14)-compounds 4( 15)-compounds Nature of P-OH amino acid (unit B) Nummularine-C type Frangulanine Integerine Amphibine-F Mucronine-A type (Pro) tY Pe type type 5( 13)-compounds 5( 14)-compounds Zizyphine-A type Scutianine-A Amphibine-B -(Pro) type type (Leu or Phe) (Pro> Table 2 4( 13)-NummuIarine-C-type cyclopeptide alkaloids bearing proline as ring bound amino acid R,"N-f R* R' Compound R1 R2 R3 Mr 1 Subfraction III9 CH3 H H 428 2 Subfraction 119 CH2C6H5 CH3 CH3 532 Table 3 4( 13)-Nummularine-C-type cyclopeptide alkaloids bearing ring bound amino acid other than proline Compound R' R2 R3 R4 R5 Mr 3 4 5 6 7 8 Daechuine-S7 Compound 220 Saltivanine-K Nummularine-S Tscheschamine Lotusine-F CH,CH(CH,),CH(CH3)CH2CH CH(CH,)CH,CH CH2C6H5 CH2C6H5 CH(CH3)CH,CH 514 514 514 520 520 520 9 10 11 12 13 Daechucyclopeptide-I (=Daechuine-S26) Daechuine-S6 Nummularine-R Daechuine-S 10 Rugosanine-B CH(CH,)CH,CH CH(CH,)CH,CH CH(CH,)CH,CH3 CH2CH6H5 CH(CH,)CH,CH 548 587 587 621 76 Natural Product Reports Table 4 5( 13)-Zizyphine-A-type cyclopeptide alkaloids R1 R4 Compound R' R2 R3 R4 R5 M - 14 Sativanine-H CH CH 557 15 Nummuiarine-P H CH 557 16 17 Rugosanine-A Nummularine-T CHO CHO CH CH 585 619 18 Daechuine-S8-1 CH CH 613 19 Daechuine-S3 CH CH 627 20 Lotusine-E CH H 64 7 21 Paliurine-B H CH 647 22 0-Desmethylmucronine-D CH H 647 23 Nummularine-0 (=N-desmethyljubanine-B) H CH Table 5 4( 14)-Frangulanine-type cyclopeptide alkaloids Compound R' R2 R3 Mr 24 Daechuine-S5 CH,CH(CH,) 486 25 N-Desmethy lmyriantine-C CH(CH,) 472 26 Discarine-F ( =N-desmethyladouetine-X) CH(CH,( CH2CH 27 Melofoline CH2CH 488 28 Discarine-E CH(CH,)CH,CH 500 29 Sanjoinine-B ( =N-desmethylfrangufoline) CH2CH(CH3)2 30 Lotusanine-A CH(CH,)CH,CH 518 31 Sanjoinine-F CH(OH)CH(CH,) 550 32 Discarine-X CH2CH(CH,)2 573 33 Scutianine-J CH(OH)C,H 600 identical with nummularine-R 11 daechuine-S5 24 with 4 Sources melonovine-A52 or p~bescine-A,~~ lotusanine-A 30 with The plant sources of the new compounds isolated can be seen adouetine-Y' ( =myrianthine-B),38~40~45~s656 discarine-X 32 in Table 12.with n~mmularine-K,~' discarine-D 35 with crenatine-A5' and AM-2 36 with ara1i0nine-B.~~ Only for AM-2 36 the relationship with aralionine-B although unresolved has been 5 Structure elucidation and stereochemistry menti~ned.~~ SanJoinine-G2 48 has also been prepared from frangufoline.4 ' The main tools for structure elucidation nowadays are mass spectroscopy (MS) and NMR spectroscopy.MS is extensively used since the various groups of cyclopeptide alkaloids frag- ment in a predictable and well documented way. Without 3 Structures of new compounds avoiding the danger of oversimplification we can claim that The structures of the new compounds isolated can be seen in there is a constant basic pattern of fragmentation in all Tables 2-1 1. cyclopeptide alkaloid groups except 4(15)-compounds. The Gournelis Laskaris and Verpoorte Cyclopeptide alkaloids 77 Table 6 4( 14)-Integerrine-type cyclopeptide alkaloids Table 9 5( 14)-Amphibine-B-type cyclopeptide alkaloids Q-$$$Y N H ko R2 R1-( N-Me R3 Compound R' R2 R3 M ~ 34 Discarine-C CH2CH(CH3) CH,CH(CH,) CH 534 Compound R R' R2 4 35 Discarine-D CH2CH(CH,) CH2C6H CH 568 -36 AM-2 CH2C6H5 CH(CH,)CH,CH H 554 Table 7 4( 14)-Amphibine-F-type cyclopeptide alkaloids -( "H* 37 Spinanine-A (M,= 440) 38 Lotusine-D (= Kdesmethyl-lotusine-A)R = H (M,= 504) 39 Lotusine-A R = Me (M,= 518) Table 8 4( 14)-Pandamine-type cyclopeptide alkaloids 46 Lotusine-C CH(CH,) H CH 617 47 Lotusine-B CH,CH(CH,) CH H 631 - reader is referred to the excellent description made by Tschesche and Kaussmann2 and to the latest review article of Gournelis et al.(in press Prog. Chem. Org. Nut. Prod.). We quote below a few fragments that are representative of the nature of the amino acid substituents of the 4(14)-type cyclopeptide alkaloids (Table 13).The base peak corresponds to fragment a. 'H NMR spectra have proved valuable for the identification and overall structure determination of these alkaloids and for decifering the relative configuration of the (3-OH amino acid. In the case of the erythro form Ju,pca. 8 Hz whereas for threo compounds Ju,pca. 2 Hz.l2-I4 l3 C NMR spectroscopy is used for the elucidation of the absolute configuration of the b-OH amino acid in case of D-erythro configuration the C-p reso-nates at 87 ppm while in L-erythro it is at 81.5 ppm and C-a resonates at 53.8 ppm for the D-erythro form and at 55 ppm for the L-erythro form (Table 14).'5,'6I3CNMR spectroscopy can be used to distinguish between cis and trans conformations when the P-OH amino acid is proline.The rule is C-Y-Pro; trans=21.2-21.6 ppm and cis=23.8-24.1 ppm (Table 15).'6,'7 Broadbent and Paul presented I3C NMR spectra of a series of alkaloids including 12 cyclopeptides.' Based on these general rules developed in recent years the stereochemistry of some cyclopeptide alkaloids has been determined. In addition Compound 40 Discarine-H 41 Discarine-L 42 Discarine-K 43 Discarine-G 44 Sanjoinine-GI 45 Sanjoinine-D (=0-methylsanjoinine-G1) 78 Natural Product Reports N-Me /Me R' R2 R3 Mr CH2CH(CH3)2 CH2CH(CH3)2 H 518 CH(CH,)CH,CH CH2CH(CH3)2 H 518 CH(CH,)CH,CH CH2C8H6N H 59 1 CH2C6H5 CH2C6H5 CH2C6H5 CH(CH,)CH2CH CH2CH(CH3)2 CH,CH(CH,)2 H H CH 552 552 566 Table 10 Linear (open) peptide alkaloids 48 Sanjoinine-G2 (= frangufoline-amido aldehyde) (M,= 538) Table 11 Neutral compounds related to cyclopeptide alkaloids w 49 Sanjoinenine (M,= 489) /\ Lo* 50 Lotusanine-B (M,= 620) we provide here some further stereochemical assignments (Table 16).6 Synthesis There have been many attempts at the total synthesis of cyclopeptide alkaloids and such efforts are still in progress and usually result in the formation of dihydro-analogues (saturated D unit). This work is well reviewed in refs. 1 5 and 6 later efforts presented in refs. 60-70. The general approach in the synthesis of cyclopeptide alka- loids is first to synthesize the open macrocycle or its dihydro- derivative and then depending on the nature of the ends of the macrocycle close the ring either by forming a peptide bond between units B and C or between units C and D (the ends are an activated carboxy group and a protected amino group that react under conditions that favour an intramolecular process) or by forming the ether linkage between units D (the end can be a phenol function) and B (the end can be a dehydro-amino acid residue).The formation of the P-aryloxyamino acid Gournelis Laskaris and Verpoorte Cyclopeptide alkaloids which was one of the most difficult problems has been successfully ove~come.~~’~~ 7 Biological activity Almost nothing is known about the physiological role of cyclopeptide alkaloids in plants. The restricted natural avail- ability of these compounds (0.0002-1%) and the lack of practical synthetic methods do not allow systematic studies on their biological properties.Antibacterial and antifungal activi- ties of some representatives of this group have already been reported in reviews. 1,2,576 In addition the following pharmaco- logical properties should be mentioned. 7.1 Sedative activity Adouetine-Z was reported to possess discrete central seda- tive activity possibly of central sympatholytic origin.71 Frangufoline showed strong sedative activity at a dose of 3 mg kg -(effect monitored by measuring the prolongation of hexobarbital induced sleeping time of mice). Additivity was observed between frangufoline and nuciferine (an aporphine alkaloid also obtained from the seeds of Zizyphus vulgaris var.spinosus).21 Sanjoinine-Ah1 the heat induced artifact of sanjoinine-A (=frangufoline) showed higher activity at the same doses as sanjoinine-A verifying the classical record on the heat treatment of sanjoin (seeds of Zizyphus vulgaris var. spinosus) appearing in Old Chinese Materia Medica (in Chinese) which described that the roasting of sanjoin makes hypnotic activity more potent. Based on the descriptions found in the Old Chinese Materia Medica sanjoin has been fre- quently used as an important and reliable hypnotic or sedative agent for the treatment of insomnia. Oriental herbal medicine doctors customarily use the drug after it has been roasted on a hot plate at high temperature.*’ 7.2 Antibacterial activity Scutianine-A -B -C and -E (as the hydrochloride salts) showed some antibacterial activity against the Gram-positive Bacillus subtilis.Scutianine-C completely inhibits develop- ment of B. subtilis at a concentration of 200 pg ml- Mauritine-A -B and -D (hydrochloride salts) showed weak antibacterial activity against B. s~btilis.~~ Rugosanine-A -B nummularine-B -R -S and amphibine-H (all 13-membered cyclopeptide alkaloids) showed antibacterial activity against Gram-negative bacteria Klebsiella pneumoniae and Escherichia ~oli.~~ The 14-membered cyclopeptide alkaloids frangufoline and nummularine-K exhibited significant anti- bacterial activity against Gram-negative bacteria K. pneumo-niae E. coli and a Gram-positive bacterium Staphylococcus a~reus.~~ Of all the compounds in this study amphibine-H (1 3-membered) showed the highest antibacterial activity against E.coli. Mucronine-F -G and -H (as the hydro- chloride salts) exhibited antibacterial activity against B. subtilis and E. ~oli.~~ 7.3 Antifungal activity Scutianine-A -B -C -D -E (hydrochloride mauritin A B C D E (hydrochloride salts)73 and mucronine-F -G -H (hydrochloride salts)74 inhibited development of Pyth ium debaryanum. Pubescine-A and abyssinine-C showed a fungicidal effect against P. debaryanum and Trichoderma ~iride.~~,~~ Frangufoline amphibine-H rugosanine-A -B and nummularine-B -K -R -S showed significant activity Table 12 Plant source index Compound Sources Family Plant part References 1 Spaeranthus indicus Asteraceae flowers 19 2 Spaeranthus indicus Asteraceae flowers 19 3 Zizyphus jujuba var.inermis Rhamnaceae stem bark 21 4 Zizyphus mucronata Rhamnaceae roots 20 5 Zizyphus sativa Rhamnaceae stem bark 22 6 Zizyphus nummularia Rhamnaceae stem bark 23,24 7 Zizyphus sativa R hamnaceae stem bark 25 8 Zizyphus lotus Rhamnaceae root bark 26 9 Zizyphus jujuba var. inermis Rhamnaceae fruits stem bark 21 10 Zizyphus jujuba var. inermis Rhamnaceae stem bark 21 11 Zizyphus nummularia Rhamnaceae stem bark 27 12 Zizyphus jujuba var. inermis R hamnaceae stem bark 21 13 Zizyphus rugosa Rhamnaceae stem bark 24,28 14 Zizyphus sativa R hamnaceae stem bark 29 15 Zizyphus nummularia Rhamnaceae stem bark 28,30 16 Zizyphus rugosa Rhamnaceae stem bark 24,3 1 17 Zizyphus nummularia Rhamnaceae stem bark 32 18 Zizyphus jujuba var.inermis Rhamnaceae stem bark 21 19 Zizyphus jujuba var. inermis Rhamnaceae stem bark 21 20 Zizyphus lotus R hamnaceae root bark 26 21 Paliurus ramosissimus Rhamnaceae roots stems 33 22 Zizyphus mucronata Rhamnaceae roots 20 23 Zizyphus nummularia Rhamnaceae stem bark 34 24 Zizyphus jujuba var. inermis Rhamn aceae stem bark 21 25 Plectronia odorata Rubiaceae aerial parts 35,36 26 Discaria febrifuga Rhamnaceae root bark 37 27 Melochia corchorlfolia Sterculiaceae aerial parts 38 28 Discaria febrifuga Rhamnaceae stem bark 39 Discaria longispina Rhamnaceae root bark 40 29 Zizyphus vulgaris var. spinosus Rhamnaceae seeds 21,41 30 Zizyphus lotus Rhamnaceae aerial parts 42 31 Zizyphus lotus R hamnaceae aerial parts 41 Zizyphus vulgaris var.spinosus R hamnaceae seeds 21,41 32 Discaria longispina R hamnaceae root bark 40 33 Scutia buxlfolia Rhamnaceae stem bark 43 34 Discaria febrifuga Rhamnaceae stem bark 44 35 Discaria febrifuga Rhamnaceae stem bark 44 36 Antidesma montana Euphorbiaceae leaves terminal branches 45 37 Zizyphus spina-christi R hamnaceae stem bark 46 38 Zizyphus lotus Rhamnaceae root bark 47 39 Zizyphus lotus Rhamnaceae root bark 47 40 Discaria febrijiuga R hamnaceae root bark 48 41 Discar ia feb r ijiuga Rhamnaceae root bark 49 42 Discaria febrijiuga Rhamnaceae roots 50 43 Discaria febrijiuga Rhamnaceae root bark 51 44 Zizyphus vulgaris var. spinosus Rhamnaceae seeds 21 45 Zizyphus vulgaris var.spinosus Rhamnaceae seeds 21,41 46 Zizyphus lotus Rhamnaceae root bark 26 47 Zizyphus lotus Rhamnaceae root bark 26 48 Zizyphus vulgaris var. spinosus R hamnaceae seeds 21,41 49 Zizyphus lotus Rhamnaceae aerial parts 42 Zizyphus vulgaris var. spinosus R hamnaceae seeds 21,41 50 Zizyphus lotus Rhamnaceae aerial parts 42 against Aspergillus niger but no activity against Cundidu tyrosine. No tetrapeptides were formed in suspension cultures albi~uns.~~ or calli that were not fed with appropriate amino acids. Interestingly field grown plants or plantlets regenerated in vitro did not produce tetrapeptides. No radiolabelling experiments were performed. It should be noted that ceanothamine-8 Biosynthesis and tissue culture E mentioned in ref.75 corresponds to ceanothamine-A There is only one paper dealing with tissue cultures and (frangulanine). biosynthesis of cyclopeptide alkaloid^.^^ According to this The biosynthetic origin of the styrylamine unit in 4( 14)- and paper calli of Ceonathus americanus did not accumulate alka- 5( 14)-type cyclopeptide alkaloids is obvious (tyrosine). Only in loids but after feeding with appropriate amino acids tetrapep- the 4( 13)- and 5( 13)-type cyclopeptide alkaloids where the tides were formed whose structures perfectly accorded with existence of a ~-(2-alkoxy-5-hydroxy)styrylamine unit can not those of the cyclopeptide alkaloids produced by the roots be attributed to a tyrosine. Studies on the biosynthetic origin of the plant. As expected the styrylamine unit arose from of the styrylamine unit would be of interest.80 Natural Product Reports Table 13 Diagnostic fragments for the identification of the amino acid moieties Position of amino acid Designation of fragment (m/z) R’ Basic terminal 7NtR5 R4 a (57+ R’ + R4 + R5) p-Hydroxy R4 c (152+ R2 + R4 + R5) d (124+ R2 + R4+ R5) + Ring-bound R3 h (217+R3) P-Hydroxy + ring-bound R3 R3 e (203+R2+R3) k (l10+R2+R3) Table 14 Assignments of the configuration of the 0-OH amino acid by NMR spectroscopy N-R4 R5 C-a shiftlppm C-/3 shiftlppm J,.,(’H-NMR)IHz D-erythro 53.8 87 8 L-erythro 55 81.5 8 threo -2 9 Conclusions With the exception of isolation and structure elucidation the field of cyclopeptide alkaloids is ‘terra incognita’.Their seda- tive and antimicrobial activities their alleged ionophore role across cell membranes and their structural complexity have mobilized research interest. Due to the poor yields from plant material or from chemical synthesis cell cultures seem an interesting method for further study of the regulation of biosynthesis of the cyclopeptide alkaloids. Such studies may lead to strategies to improve the production in plant or plant cell cultures. Gournelis Laskaris and Veruoorte Cvcloueutide alkaloids Table 15 Assignments of cis or trans conformation of proline by NMR spectroscopy C-y shift/ppm trans 2 1.2-2 1.6 cis 23.8-24.1 Table 16 Cyclopeptide alkaloids for which the stereochemistry has been determined by means of NMR spectroscopy either by the original authors (denoted ‘1’) or from the reported data by us (denoted ‘2’) Compound Configuration Assignment Reference 4 trans- P-OH-Proline 1 22 trans-P-OH-Proline 1 25 erythro- P-OH-Leucine 1 26 erythro-P-OH-Leucine 1 30 L-erythro-P-OH-Leucine 1 31 L-erythro-P-OH-Leucine 2 36 N-Me-~-Phenylalanine 1 erythro-P-OH-Phenylalanine 2 L-Isoleucine 1 49 trans-Cinnamic acid 1 threo-P-OH-Leucine 2 erythro- P-OH-Leucine 2 50 trans-Cinnamic acid 1 L-erythro-P-OH-Leucine 1 10 References 1 U.Schmidt A. Lieberknecht and E. Haslinger in The Alkuloids ed. A. Brossi Academic Press New York vol. 26 1985 pp. 299-306. 2 R. Tschesche and E. U. Kaussmann in The Alkaloids ed. R. H. F. Manske Academic Press New York vol.15 1975 pp. 165-205. 3 R. Tschesche Heterocycles 1976 4 107. 4 A. H. Shah and V. B. Pandey J. Chem. SOC. Pak. 1985 7 363. 5 K. L. Bhat and M. M. Joullie J. Chem. Educ. 1987 64 21. 6 M. M. Joullie and R. F. Nutt in Alkaloids Chemical and Biological Perspectives ed. S. W. Pelletier Wiley New York vol. 3 1984 pp. 113-168. 7 E. W. Warnhoff Fortschr. Chem. Org. Naturst. 1970 28 162. 8 T. A. Broadbent and E. G. Paul Heterocycles 1983 20 939. 9 R. J. Stonard and R. J. Andersen J. Org. Chem. 1980 45 3687. 10 R. J. Stonard and R. J. Andersen Can. J. Chem. 1980 58 2121. 11 J. C. Lagarias D. Goff F. K. Klein and H. Rapoport J. Nut. Prod. 1979 42 220 12 M. Gonzalez Sierra 0. A. Mascaretti F. J. Diaz and E. A. Ruveda J.Chem. SOC., Chem. Commun. 1972 915. 13 J. Marchand M. Pais and F.-X. Jarreau. Bull. SOC.Chim. Fr. 1971 10 3742. 14 J. Marchand F. Rocchiccioli M. Pais and F.-X. Jarreau Bull. SOC. Chim. Fr. 1972 12 4699. 15 A. F. Morel R. V. F. Bravo F. A. M. Reis and E. A. Ruveda Phytochemistry 1979 18 473. 16 M. Pais F.-X. Jarreau M. Gonzalez Sierra 0. A. Mascaretti E. A. Ruveda C.-J. Chang E. W. Hagaman and E. Wenkert Phytochemistry 1979 18 1869. 17 E. Medina and G. Spiteller Liebigs Ann. Chem. 1981 538. 18 J. C. Lagarias D. Goff and H. Rapoport J. Nat. Prod. 1979 42 220. 20 20 35 37 43 41,42 45 45 45 41,42 42 41 42 42 19 M. I. D. Chugtai I. Khokhar and A. Ahmad Sci. Int. Lahore 1992 4 151. 20 L. Barboni P.Gariboldi E. Torregiani and L. Verotta Phyto-chemistry 1994 35 1579. 21 B. H. Han M. H. Park and J. H. Park Pure Appl Chem. 1989,61 443. 22 A. H. Shah M. A. Al-Yahya S. Devi and V. B. Pandey Phyto-chemistry 1987 26 1230. 23 A. H. Shah R. M. A. Khan S. K. Maurya and V. P. Singh Phytochemistry 1989 28 305. 24 V. B. Pandey and S. Devi Planta Med. 1990 56 649. 25 A. H. Shah V. B. Pandey G. Eckhardt and G. A. Miana Heterocycles 1988 27 2777. 26 K. Ghedira R. Chemli C. Caron J.-M. Nuzillard M. Zeches and L. Le Men-Olivier Phytochemistry 1995 38 767. 27 S. Devi V. B. Pandey J. P. Singh and A. H. Shah Phytochemistry 1987 26 3374. 28 Y. C. Tripathi S. K. Maurya V. P. Singh and V. B. Pandey Phytochemistry 1989 28 1563. 29 A. H.Shah G. A. Miana S. Devi and V. B. Pandey Planta Med. 1986 52 500. 30 S. P. D. Dwivedi V. B. Pandey A. H. Shah and G. Eckhardt J. Nut. Prod. 1987 50 235. 31 V. B. Pandey Y. C. Tripathi S. Devi J. P. Singh and A. H. Shah Phytochemistry 1988 27 1915. 32 B. Singh and V. B. Pandey Phytochemistry 1995 38 271. 33 C. Yu Y.-Y. Tseng and S.-S. Lee Biochim. Biophys. Acta 1993 1156 334. 34 V. B. Pandey S. P. D. Dwivedi A. H. Shah and G. Eckhardt Phytochemistry 1986 25 2690. 35 D. Gournelis PhD Thesis Universitk Rene Descartes 1988 pp. 62-67 and 127-128. 36 D. Gournelis A.-L. Skaltsounis F. Tillequin M. Koch J. Pusset and S. Labarre J. Nut. Prod. 1989 52 306. 37 A. F. Morel R. Herzog J. Biermann and W. Voelter Z. Nutur-forsch. Anorg. Chem.Org. Chem. B 1984 39 1825. 38 R. S. Bhakuni Y. N. Shukla and R. S. Thakur Phytochemistry 1987 26 324. 39 A. F. Morel R. Herzog and W. Voelter Chimiu 1985 39 98. 40 E. C. Machado A. A. Filho A. F. Morel and F. Delle Monache J. Nut. Prod. 1995 58 548. 41 B. H. Han M. H. Park and Y. N. Han Phytochemistry 1990 29 3315. 42 M. Abu-Zarga S. Sabri A. Al-Aboudi M. Saleh Ajaz N. Sultana and Atta-ur-Rahman J. Nut. Prod. 1995 58 504. 43 A. S. Menezes M. A. Mostardeiro N. Zanatta and A. F. Morel Phytochemistry 1995 38 783. 44 M. Digel A. F. Morel H. Layer J. Biermann and W. Voelter Hoppe-Seyler’s 2. Physiol. Chem. 1983 364 1641. 45 D. Arbain and W. C. Taylor Phytochemistry 1993 33 1263. 46 F. M. Abdel-Galil and M. A. El-Jissry Phytochemistry 1991 30 1348.47 K. Ghedira R. Chemli B. Richard J.-M. Nuzillard M. Zeches and L. Le Men-Olivier Phytochemistry 1993 32 1591. 48 R. Herzog A. F. Morel J. Biermann and W. Voelter Chem.-Ztg. 1984 108 406. 49 A. F. Morel E. C. Machado and L. A. Wessjohann Phyto-chemistry 1995 39 43 1. 50 W. Voelter A. F. Morel Atta-ur-Rahman and M. M. Qureshi Z. Naturforsch. B Chem. Sci. 1987 42 467. 51 R. Herzog A. F. Morel J. Biermann and W. Voelter Hoppe-Seyler’s 2. Physiol. Chem. 1984 365 1351. 52 G. J. Kapadia Y. N. Shukla J. F. Morton and H. A. Lloyd Phytochemistry 1977 16 1431. 53 R. Tschesche D. Hillebrand and I. R. C. Bick Phytochemistry 1980 19 1000. 54 J. Marchand X. Monseur and M. Pais Ann. Pharm. Fr. 1968,26 771. 55 R. Tschesche and I.Reutel Tetrahedron Lett. 1968 35 3817. 56 V. M. Merkuza M. Gonzalez Sierra 0. A. Mascaretti and E. A. Ruveda Phytochemistry 1974 13 1279. 57 R. Tschesche M. Elgamal and G. Eckhardt Chem. Ber. 1977,110 2649. 58 M. Silva D. S. Bhakuni P. G. Sammes M. Pais and F.-X. Jarreau Phytochemistry 1974 13 861. 59 R. Tschesche L. Frohberg and H.-W. Fehlhaber Chem. Ber. 1970 103 2501. 60 A. H. Shah G. A. Miana and V. B. Pandey J. Chem. SOC. Pak. 1985 7 341. 61 U. Schmidt Pure Appl. Chem. 1986 58 295. 62 B. H. Lipshutz B. Huff K. McCarthy S. M. J. Mukarram and W. Vaccaro Abstr. Pap. Am. Chem. SOC. 1987 193 84. 63 D. M. Flanagan K. L. Bhat and M. M. Joullie J. Prakt. Chem. 1987 329 915. 64 D. M. Flanagan and M. M. Joullie Synth. Commun.1989 19 1. 65 R. J. Heffner and M. M. Joullie Tetrahedron Lett. 1989 30 7021. 66 M. M. Bowers P. Carroll and M. M. Joullie J. Chem. SOC. Perkin Truns. 1 1989 5 857. 67 R. J. Heffner and M. M. Joullie Abstr. Pap. Am. Chem. SOC. 1990 200 175. 68 D. M. Flanagan and M. M. Joullie Synth. Commun. 1990,20,459. 69 B. H. Lipshutz B. E. Huff K. E. McCarthy S. M. J. Mukarram T. J. Siahaan W. D. Vaccaro H. Webb A. M. Falick and T. A. Miller J. Am. Chem. SOC.,1990 112 7032 70 L. Williams Z. Zhang X. Ding and M. M. Joullie Tetrahedron Lett. 1995 36 7031 71 0. Blanpin M. Pais and M. A. Quevauviller Ann. Pharm. Fr. 1963 21 147. 72 R. Tschesche and E. Ammermann Chem. Ber. 1974 107 2274. 73 R. Tschesche H. Wilhelm E. U. Kaussmann and G. Eckhardt Liebigs Ann.Chem. 1974 1694. 74 R. Tschesche S. T. David R. Zerbes M. Von Radloff E. U. Kaussmann and G. Eckhardt Liebigs Ann. Chem. 1974 1915. 75 M. A. Baig D. V. Banthorpe A. A. Coleman M. D. Tampion J. Tampion and J. J. White Phytochemistry 1993 34,171. 82 Natural Product Reports

ISSN:0265-0568    

DOI:10.1039/NP9971400075

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Hot off the press Robert A. Hill" and Andrew R. Pittb aDepartment of Chemistry Glasgow University Glasgow UK G12 8QQ. E-mail bobh@chem.gla. ac. uk bDepartment of Pure and Applied Chemistry Strathclyde University Thomas Graham Building 295 Cathedral Street Glasgow UK GI 1 XL. E-mail a. r.pitt@strath. ac. uk Reviewing the recent literature on natural products and bioorganic chemistry Erinacine E 1 is a metabolite of Hericium erinaceum that stimulates nerve growth factor synthesis in astroglial cells. The structure of erinacine E 1 was determined by X-ray diffraction analysis to be a cyathane linked to a xylopyranose unit via two C-C bonds (H. Kawagishi et al. Tetrahedron Lett. 1996 37 7399). Plukenetione 2 is a natural adamantane derivative from Clusia plukenetii that probably arises biogenetically from a tetraprenylated benzophenone precursor (G.E. Henry et al. Tetrahedron Lett. 1996 37 8663). Other interesting new natural products include the tribenzylbutenolide maculalac- tone 3 from Kyrtuthrix maculans (G. D. Brown and co-workers Phytochemistry 1996 43 1083) benkarlaol 4 from Laurencia larlae (L.-M. Zeng Chin. J. Chem. 1996 14 370) 2,2'-biguaiazulenyl 5 from Calicogorgia granulosa (J. Shin and co-workers J. Nut. Prod. 1996 59 985) and dysidiolide 6 from Dysidea etheria which possesses a new Ph 1 21 3 4 \ I 5 0 bicyclic sesterterpenoid skeleton (S. P. Gunasekera et aZ. J. 7 biological activity has been shown to be due to inhibition of DNApol /?(T. Yoshida et al.Tetrahedron 1996 52 14 487). Cephalotaxidine 8 from Cephalotaxus harringtonia var. drupacea is the first example of dimeric Cephalotaxus alkaloid (I. Takano et al. Tetrahedron Lett. 1996 37 7053). Cephalo- taxidine 8 is not quite symmetrical being composed of a r? 8 homoharringtonine and 27-oxohomoharringtonine. The extra carbonyl group gives a clue to the biogenetic dimerisation mechanism. Infuscatrienol 9 from the liverwort Jungermania infusca may arise biogenetically from ring closure of an acyclic diterpene followed by methyl migration or from ring opening of a halimane intermediate (F.Nagashina et al. Chem. Pharm. Bull. 1996 44 1628). R. Sakai et al. have reported the I 6 \ Am. Chem. SOC. 1996 118 8759). The structures of the pusilatins A to D have been fully elucidated spectroscopically leading to a revision of the structure of pusilatin D 7 and their 9 Hill and Pitt Hot ofl the press ...111 0 0 10 Scheme 1 isolation from Ecteinascidia turbinata of a number of new ecteinascidins potent anti-tumour agents. They suggest that these may be biosynthetic precursors of the previously reported ecteinascidins (J. Am. Chem. SOC.,1996 118 9017). A further metabolite that appears to be formed via an intramolecular Diels-Alder reaction has been reported (Y. Zhao et al. Chem. Comrnun. 1996 2473). Ligulaverin A 10 from Ligularia veitchiania is probably formed as shown in Scheme 1. Dolabriferol 11 is a polypropionate ester from the mollusc Dolabrifera dolabrifera that is suggested to arise from a single polypropionate chain such as 12 by ring cleavage (Scheme 2) (M.Gavagnin and co-workers Tetrahedron Lett. 1996 37 12 831). 8-Amino-2-methyl-7-oxononanoic acid 13 from Streptomyces diastaticus is an inhibitor of leukotriene A hydrolase (D. G. Corley and co-workers J. Nat. Prod. 1996 59 962). It is proposed that 8-amino-2-methyl-7-oxononanoic acid 13 is a precursor of a-methylbiotin in microorganisms. Hippospongic acid A 14 from a Hippospongia sp. is probably derived by the loss of 10 carbons from a carotenoid skeleton rather than being an irregular triterpenoid (S. Ohta et al. Tetrahedron Lett. 1996 37 7765). Labelling studies by S.-W. Yang and G. A. Cordell have shown that the amino sugar moiety of staurosporine 15 from Streptomyces staurosporeus is derived from glucose (J.Nut. Prod. 1996 59 828). Previous studies by this group had established that the remaining skeletal carbons are derived from two units of tryptophan. Isotope-dilution experiments have been used to investigate the conversion of uracil 16 into 2-amino-4-carboxypyrimidine 17 the precursor of lathyrine 18 in Lathyrus tingitanus (E. G. Brown and Y. Turan Phytochem-istry 1996 43 1029). The results demonstrated that carboxy-lation precedes amination as shown in Scheme 3. [1,2-'3C,]Acetate feeding experiments have demonstrated that the ten carbon acyl residues of triopamine 19 from Triopha catalinae are derived from five intact acetate units (E. I. Graziani and R. J. Andersen Chem.Commun. 1996 2377). H. Seto and co-workers have demonstrated that the +& 0 HO 0 12 ! OH 0 HO 0 0 11 A Scheme 2 iv Natural Product Reports +C02H 13 ?co2H 14 15 mevalonate and non-mevalonate pathways for the biosynthesis of isopentenyl diphosphate are in simultaneous operation in Streptomyces aerioufer (Tetrahedron Lett. 1996 37 7979). OH C02H I I 16 I I C02H I 18 17 Extensive labelling studies on the biosynthesis of 3-amino-4-hydroxybenzoic acid 20 in Streptomyces murayanaenosis mutants MC2 and MC3 have suggested that it is synthesised from a four carbon unit from the tricarboxylic acid cycle and a three carbon unit possibly phosphoenol pyruvate (S. J. Gouldetal. J. Am. Chem.SOC.,1996 118,9228). Studies on the biosynthesis of the potent anti-cancer agents the 0 NH2 0 19 Scheme 3 20 \C02Me 21 bryostatins in cell free extracts of Bugula neritina suggest that bruostatin 1 21 is derived solely from acetate (9-adenosylmethionine and glycerol (R. G. Kerr et al. Tetra- hedron Lett. 1996,37 8305). A study of the biosynthesis of the diarrhetic shellfish poisoning (DSP) toxins as well as the storage product DTX4 has recently been reported (J. L. C. Wright and co-workers J. Am. Chem. SOC.,1996 118 8757). The authors suggest that a Beyer-Villiger step and a monooxygenase-initiated Favorskii rearrangement explain the observed labelling pattern and that this could be a common biosynthetic mechanism in all dinoflagellate polyketides.An active cell wall metabolite from Arthrinium phaeosper- mum arthrichitin 22 has been isolated as a new class of chitin synthase inhibitors that may have wide potential as insecticides and herbicides (E. K. S. Vijayakunar et al. J. Org. Chem. 1996 61 6591). J. M. Harris et al. have investigated the interaction of 5-deoxy and 4,5-dideoxy analogues of quinate 23 with type 1 and type 2 dehydroquinases and have shown that the C-4 hydroxy group appears to be important for the key imine formation in type 1 but does not affect type 2 (J. Chem. Soc. Perkin Trans. I 1996 2371). The synthesis and inter- action with porphobilinogen deaminase of a number of ana- logues of porphobilinogen including the potent competitive inhibitors and slow substrates the phosphonate 24 and a-fluorocarboxyl compounds 25 has been reported by F.J. Leeper et al. (J. Chem. SOC.,Perkin Trans. I 1996 2633 and 2643). H 22 23 24 R = CHzPO(0Et) 25 R = CHFC02H Hill and Pitt Hot 08the press X-Ray and inhibitor studies have indicated that the key to the mechanism and enantioselectivity of the class I1 Zn-dependent aldolases is the chelation of the cis-enolate form of dihydroxyacetone phosphate by the Zn2' (W. D. Fessner et al. Angew. Chem. Int. Ed. Engl. 1996 35 2219) (Scheme 4). His I His H Scheme 4 The use of a wide range of flavin analogues has been used to spectrophotometrically probe the role of FMN in chorismate synthase from Escherichia coli (P. Macheroux et al.J. Biol. Chem. 1996 271 25 851). These studies suggest that the transient intermediate observed in the presence of substrate is the protonated reduced flavin consistent with the proposed one electron mechanism. A functionalised enzyme model 26 of the active metal centre of methane monoxygenase (and ribonucleotide reductase) has been prepared by S. Menage et al. (Angew. Chem. Int. Ed. Engl. 1996 35 2353). The p-acetato- and p-0x0-bridged di-iron centre hydroxylates one of the adjacent aromatic rings in the presence of 0 or H202 (Scheme 5). The first report of a non-corrin Co3'-dependent enzyme where the Co resides in a S and a N (or 0)ligand field has been reported for the nitrile hydrolase from Rhodococcus rhodochous J1 (B. A. Brennan et al.J. Am. Chem. SOC.,1996 118 9194). 0 OMe MeO\ 0 II 26 t Me0 OH OMe Scheme 5 The structure of flavin reductase P from Vibrio harveyi has been solved to 1.8 A resolution (J. J. Tanner et al. Biochem- istry 1996 35 13 531). The reductase is a unique interlocking dimer and the selectivity for FMN and stereospecificity of the reaction can be related to the structure. The authors also discuss the possible mode of interaction with bacterial luci- ferase. A method for the direct monitoring of individual amino acids during protein folding using 2D heteronuclear NMR on 15N labelled substrates has been reported from the group of C. Dobson (Science 1996 274 1161). Evaluation of the shape and height of cross-peaks reflects the kinetic time-course of folding events during the acquisition.F. Takusagawa and S. Kamitori have shown that the peptide backbone of (9-adenosylmethionine synthetase contains a ‘real knot’ (J. Am. Chem. SOC.,1996 118 8945). K. Xu and A. M. Klibanov have shown that there appears to be little pH memory effect in cross-linked enzyme crystals in an organic solvent but that the activity can be increased 100 fold by the use of a simple buffer system in the solvent (J.Am. Chem. Sue. 1996 118 9815). It appears that microwave irradiation modestly increases the activity of lipases used in organic solvents by 2-3 fold (M.-C. Parker et al. Tetrahedron Lett. 1996 37 8383). This apparently non-thermal activation does appear to be dependent on the hydration level of the enzyme.George Pettit has reviewed his work on the search for natural productions that have anti-cancer properties (J. Nat. Prod. 1996 59 812). A symposium in print aptly titled (for this article) ‘Highlights in bioorganic chemistry’ has been published in Pure Appl. Chem. 1996 68 2009-2192. This covers a broad range of topics including catalytic antibodies biomimetic chemistry enzymology and synthesis. A short but comprehensive review of the theory and practice of combina-torial chemistry that covers a wide range of issues in the area has been published recently (F. Balkenhohl et al. Angew. Chem. Int. Ed. Engl. 1996 35,2289). vi Natural Product Reports

ISSN:0265-0568    

DOI:10.1039/NP997140iiia

出版商:RSC    

年代:1997

数据来源: RSC