16 Terpenoids and Steroids By B. A. MARPLES Department of Chemistry The University of Technology Loughborough Leicestershire LEI 1 3TU 1 Introduction The third annual volume of the Chemical Society’s Specialist Periodical Report on Terpenoids and Steroids giving comprehensive literature cover from Septem- ber 1971 to August 1972 will be available in 1973.’ Reviews have appeared on natural products derived from marine sources’ and from echinoderms3 In addition some aspects of biogenetic-type synthe~es,~ the synthetic use of chloro-olefin annelation reactions,’ and the chemistry of naturally-occurring plant-growth regulators6 have been reviewed. 2 Monoterpenoids The chemistry of thujane derivatives has been reviewed.’ Selective reduction of the conjugated double bond of unsaturated a/?-enones is achieved using Et,SiH-(Ph,P),RhCl ;thus citral is smoothly reduced to citronellal.* Cyclization of(+)-citronella1 to( +)-neoisopulegol(1) and( -)-isopulegol(2) with( Ph,P),RhCl is rep~rted.~ Remarkably the cis-product (1) is the major product.Treatment ‘Terpenoids and Steroids’ ed. K. H. Overton (Specialist Periodical Reports) The Chemical Society London 1973 vol. 3. ‘ E. Premuzic Fortschr. Chem. org. Naturstoffe 1971 29,417. J. S. Grossert Chem. SOC.Rev. 1972 1 1. D. Goldsmith Fortschr. Chem. org. Naturstoffe 1971 29 363. P. T. Lansbury Accounts Chem. Res. 1972,5 31 1. W. J. Fleming and M. E. H. Howden Pure Appl. Chem. 1972,22 67. D. Whittaker and D. V. Banthorpe Chem. Rev. 1972,37 305. * I. Ojima and T.Kogure Tetrahedron Letters 1972 5085. K. Sakai and 0.Oda Tetrahedron Letters 1972,4375. 509 510 B. A. Marples of compounds of the type (3) with mercuric trifluoroacetate or mercuric nitrate followed by borohydride reduction gives good yields of cyclized products (4).' Solvolysis of linalyl p-nitrobenzoate is accompanied by rearrangement to give cc-terpinyl p-nitrobenzoate suggesting considerable overlap of the isopropylidene (31 (4) group n-electrons with C-1 during ionization.' ' This overlap was detected from a kinetic deuterium isotope effect in the solvolysis of neryl chloride labelled with deuterium at position 6. Geranyl chloride did not show this effect and thus confirmed that the original configuration of these molecules is retained in the ionic species.l2 Nucleophilic substitution of 4-bromoisophorone (5) gives a number of rearranged products.Thus base hydrolysis leads to compounds (6),(7),and (8)(interalia)and gives no 4-hydroxyisophorone as was expected from previous reports.' (5) Further in vitro studies supporting the biogenic link between the chrysanthemyl artemisyl santolinyl and iavandulyl systems are reported by a number of groups. Yomogi alcohol (10) is the major product resulting from the solvolysis of the chrys- anthemyl derivative (9) and is accompanied by a small quantity of santolina alcohol (1l).14 Deuterium labelling establishes that the preferred conformation for reaction is as depicted in (9)." The absolute configuration of santolina alcohol at C-3 is shown to be the same as in chrysanthemyl derivatives as would be expected if the two skeletons are biogenetically linked.I6 Cleavage of the cyclopropane ring in chrysanthemic acid derivatives is dependent upon sub- stituents and can be controlled to give santolinyl artemisyl and lavandulyl skeletons.' Whereas the conversion of chrysanthemyl derivatives into tail-to- lo M. Kurbanov A. V. Semenovsky W. A. Smit L. V. Shmelev and V. F. Kucherov Tetrahedron Letters 1972 2175. I' S. Winstein G. Valkanas and C. F. Wilcox jun. J. Amer. Chem. SOC.,1972,94 2286. C. A. Bunton J. P. Leresche and D. Hachey Tetrahedron Letters 1972 2431. l3 J. N. Marx A. W. Carnick and J. H. Cox J. Org. Chem. 1972 37 2308. l4 C. D. Poulter S. G. Moesinger and W. W. Epstein Tetrahedron Letters 1972 67.l5 C. D. Poulter J. Amer. Chem. SOC.,1972 94 5515. Ih C. D. Poulter R. J. Goodfellow and W. W. Epstein Tetrahedron Letters 1972 71. L. Crombie P. A. Firth R. P. Houghton D. A. Whiting and D. K. Woods J.C.S. Perkin I 1972 642. Terpenoids and Steroids -+ a I PyO ‘cH-/L;,” 51 1 \ t Py =Me-N tail monoterpenoids was achieved previously in extremely low yield,’ the alcohols (13) and (14) are obtained satisfactorily by the solvolysis of the cyclo- propylmethyl-p-nitrobenzoate(12) or the cyclobutyl tosylate (15). 8b,c These transformations parallel those proposed for the conversion of presqualene alcohol into squalene. U The six natural pyrethrins and (+)-allethronyl (+)-trans-chrysanthemate have the 4s absolute configuration.’The natural occurrence of the campholenyl skeleton is reported for the first time ;campholenic aldehyde (16)and the epoxide (17) have been isolated from Juniperus ~omrnunis.~~ Linarioside (18) is the first natural chlorine-containing iridoid glucoside.’ (a) Ann. Reports (B) 1971 68 468; (b)C. D. Poulter 0.J. Muscio C. J. Spillner and R. J. Goodfellow J. Amer. Chem. Sor. 1972 94 5921 ;(c) R.M. Coates and W. H. Robinson ibid. p. 5920. M. J. Begley L. Crombie D. J. Simmonds and D. A. Whiting J.C.S. Chem. Comm. 1972 1276. A. F. Thomas Hefv. Chim. Acta 1972 55 81 5. I. Kitagawa T. Tani K. Akita and I. Yosioka Tetrahedron Letters 1972 419. 512 B. A. Marples 3 Sesquiterpenoids Some aspects of hydroazulene synthesis have been reviewed.’ ’New conventions for representing germacranolide sesquiterpenes are proposed to avoid the present conf~sion.’~The endo-structure for isolongifolene epoxide is supported on the assumption that the steric course of hydrogenation of 9-0x0-isolongifolene is the same as that for ep~xidation.’~ This may not be valid.The co-occurrence in Chamaecyparis nootkatensis of a-alaskene (19) and P-alaskene (20) which are members of enantiomeric series is uniq~e.’~ a-Alaskene (19) is identical with y-acoradiene and P-alaskene (20) is the enantiomer of 6-acoradiene.’ Revised structures are presented for albene (21)26 and futronolide (Z).”Fungal meta- bolism of ( f)-epoxyfarnesol allows the assignment of the R-configuration to the ( +)-form.28 Pseudoclovene a rearrangement product of caryolan-1-01 has the structure (23).29 The S absolute configuration of (+)-abscisic acid (24) has been assigned by correlation with malic acid3’ and by synthetic ~tudies.~’ Blumenols A (25) B (26) and C (27) which have the same configuration as (+)-abscisic acid (24) at the asymmetric ring carbon have been isolated from Podocarpus bl~rnei.~’ 22 J.A. Marshall Synthesis 1972 517. 23 D. Rogers G. P. Moss and S. Neidle J.C.S. Chem. Comm. 1972 142 576. 24 (a) D. V. Banthorpe A. J. Curtis and W. D. Fordham Tetrahedron Letters 1972 3865; (6)CL Ann. Reports (B),1971,68 470. 25 N. H. Andersen and D. D. Syrdal Tetrahedron Letters 1972 899. 26 K. VokaE 2.Samek V. Herout and F. Sorm Tetrahedron Letters 1972 1665.27 T. Kato T. Iida T. Suzuki Y. Kitahara and K. H. Overton Tetrahedron Letters 1972,4257. Y. Suzuki and S. Marumo Tetrahedron Letters 1972 1887. 29 R. I. Crane C. Eck W. Parker A. B. Penrose T. F. W. McKillop D. M.Hawley, and J. M. Robertson J.C.S. Chem. Comm. 1972 385. 30 G. Ryback J.C.S. Chem. Comm. 1972 1190. 31 T. Oritani and K. Yamashita Tetrahedron Letters 1972 31. 32 M. N. Galbraith and D. H. S. Horn J.C.S. Chem. Comm.. 1972 113 576. Terpenoids and Steroids 513 H 0wco2H (25) R' R2 = OH I x IR' (26) R' = H2c~OH ~2 = OH (27) R' = H2C31.0H R2 = H 0 Further synthetic approaches to the C-17 JH,33 C-18 JH,34 and imino- derivatives of the C-18 JH3' are reported. Of particular interest is the stereo- specific preparation of the intermediate (29)by cleavage of the dihydrothiopyran rings of compound (28).34d The formic acid-catalysed cyclization of the cyclopentane (30) surprisingly gave the hydroazulene (31).36 Stereoselective transannular cyclization routes to hydroazulenes are exemplfied by conversion of the cyclododecadienyl-p- nitrobenzoate (32) into the hydroazulene (33).37 &-+&OH 33 (a)R.J. Anderson C. A. Henrick J. B. Siddall and R. Zurfluh J. Amer. Chem. Soc. 1972,94,5379; (6) P. A. Grieco J.C.S. Chem. Comm. 1972,486. 34 (a)C. A. Henrick F. Schaub and J. B. Siddall J. Amer. Chem. SOC.,1972 94 5374 8647; (6) K. Mori M. Ohki A. Sato and M. Matsui Tetrahedron 1972 28 3739; (c) K. Mori ibid. p. 3747; (d) K.Kondo A. Negishi K. Matsui D. Tunemoto and S. Masamune J.C.S. Chem. Comm. 1972 13 1 1 ;(e)J. S. Cochrane and J. R. Hanson J.C.S. Perkin I 1972 361. 35 R. J. Anderson C. A. Henrick and J. B. Siddall J. Org. Chem. 1972 37 1266. 36 K. E. Harding and W. D. Nash Tetrahedron Letters 1972 4973. 3' J. A. Marshall W. F. Huffman and J. A. Ruth J. Amer. Chem. SOC.,1972,94,4691. 514 B. A. Marples PNBO H (33) A synthesis of (+)-junenol utilizes the biogenetic-type cationic cyclization of a farnesol derivative as a key step.38 The previously reported biogenetic-type cyclizations of acetylenic olefin~~’~ are modified in the absence of a good nucleo- ~hile.~’~ Thus compound (34)is converted uia the cations (35) and (36) into the ring-expanded compound (37) in CH,CI,-CF,CO,H.Attempts to cause the 1 eudesmols (38)and (39)to rearrange to eremophilane-type sesquiterpenes failed,40 whereas dihydroalantolactone (40)is converted by reaction with formic acid into compound (41)and its formate ester.41 The conversion of elemol to 01-and P-eudesmois with silver(r) ion is the first cyclization of this type.42 38 M. A. Schwartz J. D. Crowell and J. H. Musser J. Amer. Chem. Sac. 1972,94,4361. 39 (a)Ann. Reports (B) 1971,68 490; (b) W. S. Johnson M. B. Gravestock R. J. Parry and D. A. Okorie J. Amer. Chern. Soc. 1972 94 8604. 40 J. W. Huffman J. Org. Chem. 1972 37 2736. 4‘ I. Kitigawa Y. Yamazoe R. Takeda and Y. Yosioka Tetrahedron Letters 1972,4843. 42 T. C. Jain and J. E. McCloskey Tetrahedron Letters.1972. 5139. Terpenoids and Steroids methyla at ion"^ and a-hydro~ymethylation~~ of y-butyrolactones is reported. The hydroxymethyl compounds44 and the rx-methyl ~ompounds~~,~~ are readily converted into the r-methylene-pbutyrolactones. For a-methyl compounds containing cis-fused cyclohexane and y-butyrolactone rings a bromination-dehydrobromination procedure is used. Thus compound (42) is converted into the compound (44) which gives ( -)-frullanolide (46).4s The corresponding trans-compound (43) is converted into the ester (45),which on pyrolysis gives ( +)-arbusculin-B (47).’6 si,,<-* -$q+ -r-”--L 0 0 0 (42) 6P (44) 6P R = r-Br (46) 6P (43) 6cr (45) 6a R = p-PhC02 (47) 6cr Gymnomitrol (48),which was isolated from Gyrnnomitrion obtusurn has a novel carbon skeleton which could be biogenetically derived from 7-bisabolene uia a trichodiene intermediate.47 Johnston01 (49) a relative of pacifenol occurs in the red alga Laurenciajohnstonii and is identical with a previously reported ‘dibromide’ from L.~karnurai.~* Three chlorinated sesquiterpene lactones have H 0 H c1 43 G. H. Posner and G. L. Loomis J.C.S. Chem. Comm. 1972 892. 44 P. A. Grieco and K. Hiroi J.C.S. Chem. Comm. 1972 1317. 45 A. E. Greene J.-C. Muller and G. Ourisson Tetrahedron Letters 1972 2489. 46 A. E. Greene J.-C. Muller and G. Ourisson Tetrahedron Letters 1972 3375. 47 J. D. Connolly A. E. Harding and I. M. S. Thornton J.C.S.Chem. Comm. 1972 1320. 48 J.J. Sims W. Fenical R. M. Wing and P. Radlick Tetrahedron Letters 1972 195. 516 B. A. Marples been isolated from Centaurea specie^.^' The norsesquiterpenes gyridinal (50)’’ and gyridinone (51)’ have been isolated from gyrinid beetles. 4 Diterpenoids Grandiflorenic acid which is shbwn to be identical with a previously isolated and wrongly identified compound has the structure (52).52Tetrahydrogibberellin A CO H (from Sonneratia apetala) has the structure (53).53Assignment of stereochemistry at C-9 in gibbanes is assisted by a study of the ‘H n.m.r. signals for the 6-H and of the 16-carbonyl group stretching frequencies in the i.r.54 Full structural assign- ments and corrections are reported for the various oxidation products derived HO/lq-JqOH H C0,H 49 (a)A.G. Gonzalez J. Bermejo J. L. Breton and J. Triana Tetrahedron Letters 1972 2017; (b)J. Harley-Mason A. T. Hewson 0. Kennard and R. C. Pettersen J.C.S. Chem. Comm. 1972,460. (a)J. Meinwald K. Opheim and T. Eisner Proc. Nat. Acad. Sci. U.S.A. 1972 69 1208; (b)H. Schildknecht H. Neumaier and B. Tauscher Annalen 1972 756 155. s1 J. W. Wheeler S. K. Oh E. F. Benfield and S. E. Neff J. Amer. Chem. Soc. 1972,94 7589. 52 F. Piozzi S. Passannanti M. L. Marino and V. Sprio Canad. J. Chem. 1972 50 109. s3 P. Gaskin J. MacMillan S. N. Ganguly T. Sanyal P. K. Sircar and S. M. Sircar Chem. and Ind. 1972,424. 54 A. J. Baker A. C. Goudie U. R. Ghatak and R. Dasgupta Tetrahedron Letters 1972 1103. Terpenoids and Steroids from levopimaric acid with KMnO and OSO,.~~ The observation that the aldehyde (54) is rapidly autoxidized in benzene lends further support to the suggestion56b that 4-hydroxy-l9(or 18)-norditerpenoids are artefacts.CHO Selective reduction of the severely hindered 10-carboxyl group in gibberellin A (55)is effected uia the lactone (56),in which the carbonyl group is held in an accessible orientation and leads to a partial synthesis of gibberellin A, (57).5’ The C, antibiotic LL-Zl271a (58)was synthesized from a degradation product of marr~biin.~~ Selective metalation of the diene (59) with Bu”Li-TMEDA followed by reaction with the bromo-compound (60)gave racemic ar-arternisene (61).” Full details of syntheses of steviol and erythroxydiol are now available.60 0 ” W.Hen and R. C. Ligon J. Org. Chem. 1972,37 1401. 56 (a)0.Tanaka S. Mihashi I. Yanagisawa T. Nikaido and S. Shibata Tetrahedron 1972 28 4523 ;(b)cf. Ann. Reporrs (B) 1971 68 478. 57 D. H. Bowen D. M. Harrison and J. MacMillan J.C.S. Chem. Comm. 1972 808. 58 (a)W. Adinolfi L. Mangoni G. Barone and G. Laonigro Tetrahedron Letters 1972 695; (6)cf. Ann. Reporrs (B) 1970 67 412. ’’ R. J. Crawford J. Org. Chem. 1972 37 3543. B. A. Marples Acetolysis of the epimeric alcohols (62) gave (+)-14a-hybyl acetate (64) via the cation (63) which is a proposed biogenetic intermediateq6' The full details are available of the acid-catalysed cyclizations of manool which with formic acid + 'OAc fiFH8 H 163) gives (inter ah) 14a-hybyl formate.62 Treatment of levopimaric acid with concentrated sulphuric acid in dichloromethane leads through the stable cations (65) and (66) to the ring-contracted diene (67).63 Dehydrogenation of dihydro- allogibberic acid methyl ester (68)causes migration of the 7,8-bond and gives the ketone (69).64 Similar reactions in the 7-deoxygibbanes result in the migration I .+ HO,C I +OHz H of the 9,9a-bond. The bromoester (70)undergoesconsecutivedehydrobromination and demethoxycarbonylation by 0-alkyl cleavage to give the enone (71) when treated with DBN in refluxing ~ylene.~~ Decomposition of the diazoketone (72) " (a) K. Mori Y. Nakahara and M. Matsui Tetrahedron 1972 28 3217; (b) cf. Ann. '' Reports (B) 1970,67 414. D. K.M. Duc M. Fetizon and J.-P. Flament J.C.S. Chem. Comm. 1972 886. '' S. F. Hall and A. C. Oehlschlager Tetrahedron 1972 28 3155. h3 G. Mehta N. Pattnaik and S. K. Kapoor Tetrahedron Letters 1972 4947. 64 B. E. Cross and R. E. Markwell J.C.S. Chem. Comm. 1972,442. 65 D. H. Miles and E. J. Parish Tetrahedron Letters 1972 3987. 519 Terpenoids and Steroids ?Me OMe co OC @ & I (73) N ,CH (72) with CuSO gives the ketone (73) by carbene insertion into the benzylic C-10-H bond.66 Functionalization of the A-ring of the hydrofluorene (74) is achieved using the hypoiodite rea~tion,~’ and functionalization of the 4P-methyl group in the rosane (75) is achieved with lead tetra-acetate.68 All-trans-geranylgeraniolis found to be the esterifying alcohol in the bacterio- chlorophyll of the purple photosynthetic bacterium Rhodospirillurn r~brurn.~~ Cyathin A (76)and its 1,2-dehydro-derivative allocyathin B, which have been isolated from Cyathus helenae are members of a new class of diterpenes.” Aphidicolin (77) is a member of a new class of tetracyclic diterpenoids called U.R. Ghatak and S. Chakrabarty J. Amer. Chem. SOC.,1972 94 4756. 67 A. Tahara and T. Nakata Tetrahedron Letters 1972 4507. T. Nakano and A. K. Banerjee Tetrahedron 1972 28 471. 69 J. J. Katz H. H. Strain A. L. Harkness M. H. Studier W. A. Svec. T. R. Janson and B. T. Cope J. Amer. Chem. SOC.,1972,94 7938. ’O A. A. Ayer and H. Taube Tetrahedron Letters 1972 1917. 520 B. A. Marples HO\ CH,OH ,*’ aphidicolanes.’’ Three diterpene triepoxides with the novel 18(4 -+ 3)-abeo-abietane structure have been isolated from Tripterygiurn~ilfordii,’~ and a new quinone methide coleon E (78) is reported from Coleus barb~tus.~~ Neo-cembrene-A (79) is a termite trail pher~mone.’~ H .../o 5 Sesterterpenoids Retigeranic acid (81) is isolated from Lobaria retigera.” Initial cyclization of geranylfarnesyl pyrophosphate in the conformation (80) could give this novel carbon skeleton. Marine sponges have yielded a number of furanoid linear ” K. M. Brundret W. Dalziel B. Hesp J. A. J. Jarvis and S. Neidle J.C.S. Chem. Comm. 1972 1027. 72 S. M. Kupchan W. A. Court R. G. Dailey jun. C. J. Gilmore and R. F. Bryan J. Amer. Chem. SOC.,1972 94 7194. ” P.Ruedi and C. H. Eugster Helv. Chim. Acra 1972 55 1994. l4A. J. Birch W. V. Brown,J. E. T. Dorrie and B. P. Moore J.C.S. Perkin I 1972,2653. l5 M. Kaneda R. Takahashi Y. Itaka and S. Shibata Tetrahedron Letters 1972 4609. Terpenoids and Steroids 521 sesterterpene~~~,~~ and several new and similar C2 compounds which are believed to be partially degraded ~esterterpenes.’~ It is suggested that some of the C, acyclic hydrocarbons detected in African cretaceous shale could be derived from sesterterpenes.’’ 6 Triterpenoids The chemistry of the cucurbitanes has been reviewed.” Revised structures are presented for baccharis oxide (82)8 and macedonic acid.82 Marker’s ‘cr-keto- dihydrolanosteryl acetate’ is identified as 3P-acetoxy-Scr-lanost-9(1l)-en-7-0ne.~~ The tetranortriterpene bussein is shown84 to be a mixture of two compounds designated bussein A (83)and bussein B (84).I ,Me‘ OCOCH \ R (83) R = Et (84) R = Me The view that a common intermediate is involved in the biosynthesis of dammaranes and euphanes is supported by the isolation of the former in a species of Meliacemg5 Phragmalin (85) is a novel meliacin containing a nor- bornane skeleton.86 The isolation and structure determination of datiscoside (86)establishes for the first time the configuration at C-20 in the cucurbita~ins.~~ Further support for the bacterial origin of some triterpenes in sediments and oils 76 G. Cimino S. de Stafano L. Minale and E. Fattorusso Tetrahedron 1972 28 333 2 146. 77 F. Cafieri E.Fattorusso C. Santacroce and L. Minale Tetrahedron 1972 28 1579. 18 (a)G. Cimino S. de Stafano L. Minale and E. Fattorusso Tetrahedron 1972,28,267 2146; (b)CJ Ann. Reports (B) 1971 68,479. 79 C. Spyckerelle P. Arpino and G. Ourisson Tetrahedron 1972 28 5703. 80 D. Lavie and E. Glotter Fortschr. Chem. org. Naturstofle 1971 29 307. 81 (a)F. Mo T. Anthonsen and T. Bruun Acta Chem. Scand. 1972,26 1287; (6)cJ.Ann. Reports (B) 1970 67 423. 82 A. D. Zorina L. G. Matyukhina A. G. Chavva and L. A. Saltikova Tetrahedron Letters 1972 1841. 83 L. H. Briggs J. P. Bartley and P. S. Rutledge J.C.S. Perkin I 1972 581. 84 R. Hanni and Ch. Tamm J.C.S. Chem. Comm. 1972 1253. 85 S. S. Cascon and K. S. Brown Tetrahedron 1972 28 31 5. 86 R. R. Arndt and W.H. Baarchers Tetrahedron 1972 28 2333 cf. ref. 84. 81 S. M. Kupchan C. W. Sigel L. J. Guttman R. J. Restivo and R. F. Bryan J. Amer. Chem. Sor. 1972,94 1353. 522 B. A. Marples 0 HO 0 is provided by the isolation from Messel oil shale of homohopane which could arise by microbiological methylation of the 3-deo~y-triterpene.~~ The degraded limonoids odoratin (87)89 and calodendrolide (88)’’ are reported in natural sources. The latter is the logical precursor of fraxinellone for which a total synthesis is reported.” ..&o H 0 A. Ensminger P. Albrecht G. Ourisson B. J. Kimble J. R. Maxwell and G. Eglinton Tetrahedron Letters 1972 3860. 89 W. R. Chan D. R. Taylor and R. T. Aplin Tetrahedron 1972 28 431. 90 J. M. Cassady and C.4.Liu J.C.S. Chem. Comm. 1972 86. 91 Y. Fukuyama T. Tokoroyama and T. Kubota Tetrahedron Letrers 1972 3401. Terpenoids and Steroids A total synthesis of fusidic acid is rep~rted,’~ and the fusidic acid carbon skeleton is obtained by BF,-catalysed rearrangement of 3P-acetoxy-4/?-demethyl-9,11 a-epo~y-5a-lanostane.’~ The perhydrophenanthrene (89) with the trans-syn-trans-configurationof fusidic acid is prepared by BF,-catalysed rearrangement of the 5,6P-e~oxide.’~ (89) 1-Alkyl substituents in A1(’)-2-octalones and related systems are as important as angular substituents in influencing the stereoselectivity of reductive alkyla- tion.’’ Biogene tic- type total syntheses of te tracyclic’ and pen tacyclic’ ’ triterpenes continue to be studied.This very elegant work is exemplified by the synthesis of isoeuphenol(91) and 23,25-dihydro-A1 3(1 ’)-protosterol (93) from the all-chair epoxide (90) and its chair-boat-chair conformer (92) respectively. Deuterium (92) (93) 92 W. G. Dauben G. Ahlgren,T. J. Leitereg W. C. Schwarzel and M. Yoshioko J. Amer. Chem. SOC.,1972,94,8593. y3 R. Kazlauskas J. T. Pinhey and J. J. H. Simes J.C.S. Perkin I 1972 1243. 94 R. E. Ireland and U. Hengarter J. Amer. Chem. SOC.,1972 94 3652. 9s (a)P. T. Lansbury and G. E. DuBois Tetrahedron Letters 1972 3305; (b) J. W. ApSimon P. Baker J. Buccini J. W. Hooper and S. Macauley Canud. J. Chem. 1972 50 1944. 96 E. E. van Tamelen and R. J. Anderson J. Amer. Chem. Soc. 1972,94 8225. 97 (a) E. E. van Tamelen R. A.Holton R. E. Hopla and W. E. Konz J. Amer. Chern. SOC.,1972 94 8228; (6) E. E. van Tamelen M. P. Seiler and W. Wierenga ibid. p. 8229. 524 B. A. Marples incorporation into isoeuphenyl acetate produced by D +-catalysed backbone rearrangement of euphenyl acetate indicates that a protonation-deprotonation mechanism is largely involved and that protonated cyclopropanes are probable intermediate^.^^ The unusual BF,-catalysed rearrangement of the P-amyrin dienol (94) to the or-amyrin enone (95) is reported.99 The bromine-initiated rearrangement of the tirucall-7-ene (96) to the 7or-bromoapotirucall-14-ene (97) takes place via the 7a,8a-bromonium ion 24,25-dibr0mide.’~~~’O~ The shift of the 13-Me to position 14 is thought to be sterically inhibited by the 7a-bromine.Br AcO . (96) (97) 7 Steroids Two useful volumes on a variety of preparative methods applied to steroid systems have appeared.’” A review on some aspects of biomimetic chemistry has been published.’ O3 The absolute configurations of doisynolic acid (98)’04 and wortmannin (99)loS are reported. The ‘cholestane-3,4,6-trione’of Windaus and Kuhr is now shown to be the 3-ethyl ether of the corresponding dienone 98 Y. Nakatani G. Ponsinet G. Wolff J. L. Zundel and G. Ourisson Tetrahedron 1972 28 4249; c’ ref. 112. 99 R. Leonard and J. B. Thomson J.C.S. Chem. Comm. 1972 1281. loo T. G. Halsall and R. J. Weston J.C.S. Chem. Comm. 1972 1212. lo’ C’ Ann. Reports (B),1970 67 421. O2 ‘Organic Reactions in Steroid Chemistry’ ed.J. Fried and J. A. Edwards Van Nostrand Reinhold New York 1972 vols. 1 and 2. lo’ R. Breslow Chem. SOC.Rev. 1972 1 553. Io4 J. Iriarte and P. Crabbe J.C.S. Chem. Comm. 1972 110. lo5 (a)T. J. Petcher. H.-P. Weber and Z. Kis J.C.S. Chem. Comm. 1972 1061; (6) J. MacMillan T. J. Simpson and S. K. Yeboah ibid.,p. 1063; (c) J. MacMillan A. E. Vanstone and S. K. Yeboah J.C.S. Perkin I 1972 2898. Terpenoids and Steroids diol'06 and inotodiol is shown to have a 22-OH group.'" It is suggested that the ergosterol peroxide which has been reported in a number of fungal extracts is an artefact arising from natural pigment-sensitized photo-oxygenation. '** Phenol to dienone rearrangements in superacid media are reported,"' and the generality of the 'medium effect' in dienone-phenol rearrangements is questioned.' lo The HC1-catalysed rearrangement of the seco-steroid (100) to the tricyclo[5,2,1,03~8]decan-2-one (101) is remarkable.' ' Further studies on backbone rearrangements are reported.Deuterium incorporation into the products of rearrangment of 3a-amino- and 3P-dimethyl- amino-pregn-5-en-20-one in D2S0 indicates that a protonation-deprotonation mechanism is involved and that in the latter case protonated cyclopropane and/or spiro-cation intermediates are involved. ' ' Other rearrangements of 3-amino-As-compounds are reported and the importance of the reaction medium on the course of these reactions is noted.' l3 The importance of C/D intracyclic strain in promoting backbone rearrangements is again illustrated in amino-' l4 and other steroids."' The isomerization of the enone (102) to its 14P-isomer '06 J.T. Pinhey and E. Rizzardo J.C.S. Perkin I 1972 1358. lo' F. De Reinach-Hurtzbach and G. Ourisson Tetrahedron 1972,28 2259. '08 J. Arditti R. E. M. H. Fisch and B. H. Flick J.C.S. Chem. Comm.. 1972 1217. 109 (a)J.-M. Coustard J. P. Gesson and J.-C. Jacquesy Tetrahedron Letters 1972,4929; (6)J.-M. Coustard and J.-C. Jacquesy ibid. p. 1341. 'lo H. J. Shine and C. E. Schoening J. Org. Chem. 1972 37 2899. 'I1 T. R. Kasturi R. Ramachandra and K. M. Damodaran Tetrahedron Letters 1972 5059. M.-M. Janot F. Frappier J. Thierry G. Lukacs F.-X. Jarreau and R. Goutarel Tetrahedron Letrers 1972 3499; cf. ref. 98. 'I3 (a)F. Frappier M.Pais and F.-X. Jarreau Bull. Sac. chim. France 1972 610; (b)F. Frappier and F.-X. Jarreau ibid. p. 625. 'I4 F. Frappier J. Boivin and F.-X. Jarreau Compt. rend. 1972 274 C 2190. 'I5 (a)J. Bascoul D. Nicolaidis and A. Crastes de Paulet Bull. SOC. chim. France 1972 184; (6)J. Bascoul E. Noyer and A. Crastes de Paulet ibid.. p. 2744. 526 B. A. Marples in HF-SbF involves an interesting reversible protonation-deprotonation backbone rearrangement.' The 3P,SP-bridge in the epoxide (103) facilitates backbone rearrangement.' The full details of backbone and related rearrange- ments of 9-and 10-hydroxy-5P-methyl compounds and their susceptibility to substituent and reaction media variations are discussed.' l8 A dependence of the stereoselectivity of dienolate alkylation on solvent is noted.' l9 Selective hydrogenation of the up-enones to the saturated ketones is achieved using a combination of Fe(CO) and NaOH in aqueous methanol.'20 The stereochemistry of the selective reduction of the dienone (104) to the enone (105) with Ph,SnH is controlled by the configuration of the 12-aceto~y-group.'~' The 11-keto-group of the dienedione (106) may be reduced selectively if the 3-carbonyl is protected as a sodium or lithium enolate.lZ2 ' J.-C.Jacquesy R. Jacquesy and G. Joly Tetrahedron Letters 1972 4739. ' J. Wicha Tetrahedron Lerters 1972 2877. I*' J. G. Lloyd Jones and B. A. Marples J.C.S. Perkin I 1972 792. 'I9 Y. Nakadaira J. Hayashi H. Sato and K. Nakanishi J.C.S.Chem. Comm. 1972,282. lZo R. Noyori I.Umeda and T. Ishigami J. Org. Chem. 1972 37 1542. 12' U. Pommerenk H. Sengewein and P. Welzel Tetrahedron Letters 1972 341 5. ''' D. H. R. Barton R. H. Hesse M. M. Pechet and C. Wiltshire J.C.S. Chem. Comm. 1972. 1017. Terpenoids and Steroids Reaction of 3~-hydroxy-A5-steroids with dialkyl or diary1 phosphites in the presence of acid provides a new etherification procedure.' 23 Cyclic carbonates are useful acid-stable protecting groups for 20,21- 17,21-,and 17,20-diols.' 24 The trityl cation and the tris-(p-bromopheny1)aminium cation-radical are very efficient catalysts for the oxygenation of ergosteryl acetate.I2' The reactive species (107) is formed in the trityl cation-catalysed process by reaction between (107) (108) ground-state oxygen and the photo-excited triplet state of the trityl cation.The steroidal oxetans (108) give the acetals (109) on reaction with BF and ace- tone.'26 The preparation of the annulene (110) is rep~rted.'~' (1 10) Functionalization of saturated steroids at C-5 and C-14 is achieved by irradia- tion in the presence of peracetic acid,12* whereas irradiation in the presence of CC1,Br or C,H,IC12 resulted in functionalization predominantly at C-9.'29 The isolation of the pyrrolidine (111) from the photolysis of the corresponding (1 11) 12.3 Y. Kashman J. Org. Chem. 1972 37 912. I24 (a) M. L. Lewbart J. Org. Chem. 1972,37 1233; (b)M. L. Lewbart ibid.,p. 3892. 125 D. H. R. Barton G. Leclerc P. D. Magnus and I. D. Menzies J.C.S. Chem. Comm. 1972,447.I26 Gy. Schneider I. Weisz-Vincze A. Vass and K. Kovacs J.C.S. Chem. Comm. 1972 713. 127 P. H. Bentley M. Todd W. McCrae M. L. Maddox and J. A. Edwards Tetrahedron 1972,28 141 1. I28 A. Rotman and Y. Mazur J. Amer. Chem. Sac. 1972,946228. I29 R. Breslow J. A. Dale P. Kalicky S. Y. Liii and W. N. Washburn J. Amer. Chem. SOC.,1972 94 3276. B. A. Marples 6fi-azide supports the existence of a discrete nitrene.13' The liquid-phase photo- decarbonylation of the py-epoxyketone (112) to the olefin (113) is accompanied by hydride shifts from C-7 to C-5 and from C-8 to C-7.' ' The photoaddition of butadiene to 17~-acetoxyandrost-4,6-dien-3-one ( 114).'32 remarkably gives the compound OAc :-(I 14) Further steroidal carboxylic acids are reported in and four D-ring aromatic steroids including nicandrenone (115),have been isolated from the insect-repellant plant Nicandra physaloides.' 34 Withanicandrin (1 16)is the first HO '0 A.Pancrazi Q. Khuong-Huu and R. Goutarel Tetrahedron Letters 1972 5015. I3l R. J. Chambers and B. A. Marples J.C.S. Chem. Comm. 1972 1122. 132 G. R. Lenz Tetrahedron Letters 1972 3027. (a)W. K. Siefert E. J. Gallegos and R. M. Teeter J. Amer. Chem. Sac. 1972,94 5880 8647 ;(6)CJ Ann Reports (B),1971 68 491. 134 (a)R. B. Bates and D. J. Eckert J. Amer. Chem. SOC.,1972,94 8258; (6)M. J. Begley L. Crombie P. J. Ham and D. A. Whiting J.C.S. Chem. Comm. 1972 1250. Terpenoids and Steroids ikemaoyl-0 OH natural 12-0x0-withanolide to be isolated,' 35 and glycocynanchogenin (117) is a novel polyoxypregnane.36 3,25-Dihydroxy-24-methylcholest-5-ene is the first C-25 oxygenated marine ster01.'~' The principal sterols of the marine sponge Aplysina aerophoba have the unusual 26-methyl side-chain and are 24,26-dimethylcholest-5-en-3P-ol(aplysterol) and 24,28dehydroaplysterol. 38 A number of starfish species yield the aglycone (118) and several other minor novel compounds.139 Asynthesis of the aglycone (118)is rep~rted.'~' Synthetic studies on antheridiol (119)are reported by three groups.141 The synthesis of the diene (120)is achieved by dehydrobromination of 22,23-dibromo-SP-ergostane with DBN.14' 135 I. Kirson D. Lavie S. S. Subramanian P. D. Sethi and E. Glotter J.C.S. Perkin I 1972 2109.13' T. Yamagishi K. Hayashi R. Kujama and H. Mitsuhashi Tetrahedron Letters 1972,4005. 13' J. P. Engelbrecht B. Tursch and C. Djerassi Steroids 1972 20 121. 13' P. De Luca. M. De Rosa L. MinaIe and G. Sodano J.C.S. Perkin I 1972 2132. 139 (a)Y. M. Sheikh B. M. Tursch and C. Djerassi J. Amer. Chem. Soc. 1972,94 3278; (6)Y.Shimizu ibid. p. 4051 ;(c) S. Ikegami Y. Kamiya and S. Tamura Tetrahedron Lerrers 1972 1601 ; (4 S. Ikegami Y. Kamiya and S. Tamura ibid.,p. 3725; (e) Y. M. Sheikh B. Tursch and C. Djerassi ibid. p. 3721. 140 D. S. H. Smith and A. B. Turner Tetrahedron Letters 1972 5263. 14' (a)T. C. McMorris T. Arunachalam and R. Seshadri Tetrahedron Letters 1972 2673 ;(b)G. A. Smith and D. H. Williams J.C.S. Perkin I 1972,28 I I ;(c)3. A.Edwards J. Sundeen W. Salmond I. Iwadare and J. H. Fried Tetrahedron Letters 1972 791 142 A. B. Garry J. M. Midgley W. B. Whalley and B. J. Wilkins J.C.S. Chem. Comm. 1972 167. 530 B. A. Marples OH (1 19) Studies of micro biological hydroxylations of mono-and di-oxygeneated 5a-androstanes are reported using Aspergillus ochraceus and Calonectria de~0ra.I~~ Oxygen functions in rings A and D act as primary directing groups. Other studies in this area include the use of Curvularia lunata and Coniosporium rhizophillum with pregnane derivatives. 144 143 (a)A. M. Bell J. W. Browne W. A. Denny Sir E. R. H. Jones A. Kasal and G. D. Meakins J.C.S. Perkin I 1972,2930; (b)A. M. Bell W. A. Denny Sir E. R. H. Jones G. D. Meakins and W. E. Miiller ibid.p. 2759; (c) A. M. Bell P. C. Cherry I. M. Clark W. A. Denny Sir E. R. H. Jones G. D. Meakins and P. D. Woodgate ibid. p. 208 1. 144 (a) G. Cleve G.-A. Hoyer K. Kieslich and H. Wieglepp Chem. Ber. 1972 105 658; (h)V. Schwarz and J. Protiva Coll. Czech. Chem. Comm. 1972 37 1577.