17 Terpenoids and Steroids By B. A. MARPLES Department of Chemistry The University of Technology 1oughborough Leicestershire LEI I 3TU 1 Introduction The fourth annual volume of the Chemical Society’s Specialist Periodical Report on Terpenoids and Steroids,’ giving comprehensive literature cover from September 1972 to August 1973 will be available during 1974. Of general relevance to this section are reviews on biogenetic syntheses of terpenes,2 insect pheromone^,^ and sex attractants of plants and animal^.^ 2 Monoterpenoids It is agreed by two groups that the tetrahomomonoterpene (1) from the codling moth has the (6Z)-~onfiguration.~*~ However despite two independent synthese~,~~*~~ the configuration of the 2,3-double bond is in doubt. A synthesis of (+)-grandis01 (2) a constituent of the male boll weevil pheromone employs zerovalent nickel to catalyse the dimerization of isoprene.’ Regioselective cycloaddition of yy-dimethylaconic acid with isoprene leads to a novel synthesis of (f)-menthone,8 and total syntheses of (&)-a-and (+)-Q-pinene employ the ‘Terpenoids and Steroids’ ed.K. H. Overton (Specialist Periodical Reports) The Chemical Society London 1974 vol. 4. T. Money ‘Progress in Organic Chemistry’ ed. W. Carruthers and J. K. Sutherland Butterworths London 1973 p. 29. (a) D. A. Evans and C. L. Green Chem. SOC.Rev. 1973 2 75; (6) J. G. MacConnell and R. M. Silverstein Angew. Chem. Internat. Edn. 1973 12 644. L. Jaenicke and D. G. Muller Fortschr. Chem. org. Nafurstofle 1973 30,62.(a) S. B. Bowlus and J. A. Katzenellenbogen Tetrahedron Letters 1973 1277; (b) S. B. Bowlus and J. A. Katzenellenbogen J. Org. Chem. 1973 38 2733. (a) M. P. Cooke jun. Tetrahedron Letters 1973 1281; (6) M. P. Cooke jun. ibid. p. 1983. ’ W. E. Billups J. H. Cross and C. V. Smith J. Amer. Chem. SOC.,1973,95 3438. S. Torii T. Oie and H. Tanaka Tetrahedron Letters 1973. 2471. 549 B. A. Marples conversion of the benzylidene tosylate (3) into the bicyclo[3,1,1 Iheptane (4)with NaH-MeOCH,CH,OMe.' Cyclization of the enantiomers of dihydromyrcene with AcOH-H,SO unexpectedly gave cyclohexanes [e.g. (5)+(6)] stereo-specifically." Citral may be converted viu an optically active pyrrolidine enamine into optically active a-cyclocitral.' ' Treatment of a-pinene with IN,-RCN leads to the azidotetrazole (7) by a 'Hassner-Ritter' reaction.' The reactions of a-pinene (inter alia) with chloro- sulphonyl isocyanate are rep~rted,'~ and the conversion of camphor to nopinone (9)is achieved uia the mesylate (8) which rearranges readily in MeO-MeOH.' Junionone (10) is the first monocyclic cyclobutane monoterpenoid to be isolated from vegetable sources (Juniperus cornrnunis L.).The novel mono- terpene (11) was isolated from the same source.I6 Two novel chorine- and CH,OTs 0 (3) (4) R = CHPh (9) R = H H. T. Thomas and A. G. Fallis Tetrahedron Letters 1973 4687. lo H. R. Ansari Tetrahedron 1973 29 1559. ' I S. Yamada M. Shibasaki and S. Terashima Tetrahedron Letters 1973 377; 381.(a)S. Ranganathan D. Ranganathan and A. K. Mehrotra Tetrahedron Letters 1973 2265; (6) D. Ranganathan S. Ranganathan and A. K. Mehrotra Synthesis 1973 356. I3 T. Sasaki S. Eguchi and H. Yamada J. Org. Chem. 1973 38 679. l4 J. V. Pankstelis and B. W. Macharcia Tetrahedron 1973 29 1955. ' A. F. Thomas and M. Ozainne J.C.S. Chem. Comm. 1973 746. l6 A. F. Thomas Helv. Chirn. Acta 1973 56 1800. Terpenoih and Steroids 55 1 bromine-containing monoterpenes (12)' and (13)18 have been isolated from the sea hare Aplysia californica which feeds on the halogen-containing species of algae. Rose oxide is reported in the secretions of an insect for the first time.Ig 3 Sesquiterpenoids Further evidence is presented in favour of the endo-structure for isolongifolene epoxide,20 from which the kinetic product of rearrangement is the ketone (14).Paradisiol (15) and intermedeol are shown to be identical rather than epimeric at C-4 as originally supposed.21 The proposed (9-configuration for ( +)-cis-and (+)-trans-abscisic acid22e is supported by c.d.22n and 0.r.d. spectra.226 and other data.22c*d Resolution of ( f)-trans-abscisic acid via the brucine salts followed by U.V. trans-to-cis isomerization provides an improved resolution of the cis-enanti~mers.~~ Confirmation of the absolute configuration (S)of the asymmetric ring carbon of blumenols A (16)and B (17) is established by chemical correlation with ( +)-abscisic and the side-chain asymmetric carbon is shown to have the (R)-config~ration.~~' Reassignment of absolute configurations I1 (a) D.J. Faulkner and M. 0. Stallard Tetrahedron Letters 1973 1171; (b) M. R. Willcott R. E. Davis D. J. Faulkner and M. 0.Stallard ibid.. p. 3967. I8 D. J. Faulkner M. 0.Stallard J. Fayos and J. Clardy J. Amer. Chem. SOC. 1973 95 341 3. 19 G. Vidari M. De Bernardi M. Pavan and L. Ragozzino Tetrahedron Letters 1973 4065. 20 (a) G. Mehta and S. K. Kapoor Tetrahedron Letters 1973 497; (6) cf. Ann. Reports (B) 1972 69 512. 21 J. W. Huffman and L. H. Zalkow Tetrahedron Letters 1973 751. 11 (a) G. Ohloff E. Otto V. Rautenstrauch and G. Snatzke Hefu. Chim. Acta 1973 56 1874; (6)N. Harada J. Amer. Chem. SOC.,1973,95,240; (c)M.Koreeda G. Weiss and K. Nakanishi ibid. p. 239; (d)K. Mori Tetrahedron Letters 1973 2635; (e) cJ Ann.Reports (B) 1972 69 512. 23 J. C. Bonnafous J.-C. Mani J.-L. Olivk and M. Mousseron-Canet Tetrahedron Letters 1973 11 19. 24 (a) M. N. Galbraith and D. H. S. Horn J.C.S. Chem. Comm. 1973 566; (6) cf. Ann. Reports (B) 1972 69 512; (c) G. Weiss M. Koreeda and K. Nakanishi J.C.S. Chem. Comm. 1973 565. 552 B. A. Marples are reported for ( -)-campherenone (18) and the related ( +)-epicampherenone ( -)-P-santalene and ( +)-epi-P-~antalene.~' Several new approaches to a-methylenebutyrolactones are reported.26 The butyrolactones are a-carboxylated or a-formylated and then suitably modified.26"*b9',d An interesting alternative is exemplified by the rearrangement of the cyclopropylmethanol ester (19) to the a-methylenebutyrolactone (20).26r Routes to hydroazulenes continue to be of interest and are exemplified by the formic acid-catalysed cyclization of the chloro-olefin (21) to the hydroazulene (22),27and by a photochemical conversion of the By-unsaturated ketone (23) to the hydroazulene (24).28A biogenetic-type cyclization of the germacrone (25) to the guaiane (26) is achieved with acetic acid in thi~phenol.~' Syntheses of the non-isoprenoid B-gorgene (28) are rep~rted,~' including a one-step biogenetic transformation from maaliol (27).30bThe biogenetic-type conversion of the bicyclic olefin (29) into ( f)-cedrone (30) provides a synthesis of ( f)-cedrene and (_+)-~edrol.~' Two groups report the synthesis of the bicyclic compound (31) as a key intermediate in a general non-annelation approach to e~desrnanes.~~ A synthesis of (i-)-nootkatone does not employ the Robinson 25 G.L. Hodgson D. G. MacSweeney R. W. Mills and T. Money J.C.S. Chem. Comm. 1973 235. 26 (a) K. Yamada M. Kato and Y. Hirata Tetrahedron Letters 1973 2745; (6) P. A. Grieco and K. Hiroi J.C.S. Chem. Comm. 1973 500; (c) A. D. Harmon and C. R. Hutchinson Tetrahedron Letters 1973 1293; (d)R. C. Ronald ibid. p. 3831 ;(e) P. F. Hudrlik L. R. Rudnick and S. H. Korzeniowski J. Amer. Chem. SOC. 1973 95 6848. 27 (a)P. T. Lansbury P. M. Workulich and P. E. Gallagher Tetrahedron Letters 1973 65; (6)CJ Ann. Reports (B) 1972 69 513. 28 R. E. Carlson R. L. Coffin W. W. Cox and R. S. Givens J.C.S. Chem. Comm. 1973 501. 29 M. Iguchi M.Niwa and S. Yamamura Tetrahedron Letters 1973 1687. 30 (a) R. K. Boeckman jun. and S. M. Silver Tetrahedron Letters 1973 3497; (b)S. K. Paknikar and V. K. Sood ibid. p. 4853. 31 E. J. Corey and R. D. Balanson Tetrahedron Letters 1973 3153. 32 (a)R. B. Miller and R. D. Nash J. Org. Chem. 1973 38 4424; (6) G. H. Posner and G. L. Loomis ibid. p. 4459. Terpenoids and Steroids (25) (29) (30) annelation but involves cyclization of the intermediate trienone (32) to the bicyclic compound (33).33 The cyclopentane (34) is converted stereospecifically into the enol acetate (35) and thence to guai01.~~ Syntheses of #?-vetivone and (32) (33) related compounds are rep~rted,~'as are syntheses of a-ac~renol,~~'' B-and y-and a-a~oradiene.~ ac~renol,~~",~ ' A novel lactone spiroannelation procedure involving the reaction of the thioester (36) with selenious acid in benzene gave (+)-bakkenolide A (37).38 Two groups report the synthesis of gyridinal the norsesquiterpene recently isolated from gyrinid beetle^.^' 33 K.P. Dastur J. Amer. Chem. SOC.,1973 95 6509. 34 N. H. Andersen and H.-S. Uh Tetrahedron Letters 1973 2079. 35 (a) P. M. McCurry jun. and R. K. Singh Tetrahedron Letters 1973 3325; (b) P. M. McCurry jun. R. K. Singh and S. Link ibid. p. 1155; (c) G. Stork R. L. Danheiser and B. Ganem J. Amer. Chem. SOC.,1973 95 3414; (d)K. Yamada H. Nagase Y. Hayakawa K. Aoki and Y. Hirata Tetrahedron Letters 1973,4963; (e)K. Yamada K. Aoki H. Nagase Y. Hayakawa and Y. Hirata ibid. p. 4967.36 (a)1. G. Guest C. R. Hughes R. Ramage and A. Sattar J.C..S. Chem. Comm. 1973 526; (b)W. Oppolzer Helu. Chim. Acra 1973 56 1812. 37 J. N. Marx and L. R. Norman Tetrahedron Letters 1973 4375. 38 D. A. Evans and C. L. Sims Tetrahedron Letters 1973 4691. 39 (a)J. Meinwald K. Opheim and T. Eisner Tetrahedron Letters 1973 281 ;(b) C. H. Miller J. A. Katzenellenbogen and S. B. Bowlus ibid. p. 285; (c) cf. Ann. Reports (B) 1972 69 516. 554 B. A. Marples HI (ia CHOAc A number of new halogenated sesquiterpenes isolated4* from Laurencia species of algae include prepacifenol (38),40"a precursor of the recently reported pacifenol and oppositol (39),40bwhich is a member of a new skeletal class. A new JH (40) is reported from the tobacco hornworm Chlorochrymorin (41)42 and arteannuin B (42)43 are two new types of sesquiterpene lactones and cyclo- seychellene(43),"4 a-pompene (44),45and ( + )-2,idiepi-B-cedrene (45)46 are new hydrocarbon members.a-Cedrene is the first example of a sesquiterpene to be isolated from fossil 40 (a) J. J. Sims W. Fenical R. M. Wing and P. Radlick J. Amer. Chem. SOC.,1973 95 972; (b) S. S. Hall D. J. Faulkner J. Fayos and J. Clardy ibid. p. 7187; (c)A. G. Gonzalez J. Darias and J. D. Martin Tetrahedron Letters 1973 3625; (d) A. G. Gonzalez J. Darias and J. D. Martin ibid. p. 2381. 41 K. J. Judy D. A. Schooley L. L. Dunham M. S.Hall B. J. Bergot and J. B. Siddall Proc. Nat. Acad. Sci. U.S.A. 1973 70 1509. 42 T. Osawa A. Suzuki S. Tamura Y.Ohashi and Y.Sasada Tetrahedron Letters 1973 5 135.43 D. JeremiC A. JokiC A. Behbud and M. Stefanovic Tetrahedron Letters 1973 3039. 44 S. J. Terhune J. W. Hogg and B. M. Lawrence Tetrahedron Letters 1973,4705. A. Matsuo T. Maeda M. Nakayama and S. Hayashi Tetrahedron Letters 1973 4131. T. Norin and S. Sundin Tetrahedron Letters 1973 17. 47 A. G. Douglas and P. J. Grantham Chem. and fnd. 1973 37. Terpenoids and Steroids 4 Diterpenoids The quassinoid bitter principles are reviewed.48 The revised structure (46) is presented for isoincensole oxide.49 Fusicoccin H (47) is isolated and shown to be a biogenetic precursor of fusicoccin suggesting that the latter is a diterpene rather than a degraded sester-terpene as previously thought. ’O Corrected structures are presented for products of the reductive backbone-rearrangements of certain resin acid derivatives.’ * a-D-gluCOSyl I (48) R’ = H,R2 = Me (47) (49) R1= Me,R2 = H Chlorosulphonic acid-catalysed rearrangement of levopimaric acid’2a gave mixtures of the trienes (48) and (49) whereas the previously reported reaction with sulphuric acid gave ring-contraction produ~ts.’~~ The rearrangement of the tosylate (50)to the diene (51)is analogous to that proposed for the biosynthetic 48 J.Polonsky Fortschr. Chem. org. Naturstofle 1973 30 101. 49 M. L. Forcellese R. Nicoletti and C. Santarelli Tetrahedron Letters 1973 3783. 50 K. D. Barrow D. H. R. Barton Sir E. Chain U. F. W. Ohnsorge and R. P. Sharma J.C.S. Perkin I 1973 1590. 51 J.W. Huffman and J. J. Gibbs J. Org. Chem. 1973.38 2732. 52 (a)G. Mehta and S. K. Kapoor Tetrahedron Letters 1973 2385; (b) cJ Ann. Reports (B) 1972 69 518. B. A. Marples do. C0,Me transformation of atisine diterpenoid alkaloids to the aconitine type.53 The ent-beyer-15-ene-l2-p-tosylhydrazone (52)is converted with sodium borohydride into the en?-atis-13-ene (53)via a 1.2-vinyl shift.54 A 1,2-vinyl shift occurs in the rearrangement5’ of the pimarane (54)into the cleistanthane (55). However NNHTs (52) (53) OH (54) attempts to rearrange a pimarane into a cassane were unsucce~sfuI.~~ Progress has been made in a new general approach towards the inversion of the C-4-substituents in isopimaric acid,57 which is converted through the cyclobutanone (56) into the nitrile (57).The boron trifluoride-catalysed rearrangement of the epoxide (58) to the lactone (59) is the key step in a synthesis of rosenonolactone from podocarpic 53 W. A. Ayer and P. D. Deshpande Canad. J. Chem. 1973 51 77. 54 K. H. Pegel L. P. L. Piancenza L. Phillips and E. S. Waight J.C.S. Chem. Comm. 1973 552. ” G. A. Ellestad M. P. Kunstmann and G. 0.Morton J.C.S. Chem. Comm. 1973 312. ” J. P. Johnston and K. H. Overton J.C.S. Perkin I 1973 853. ’’ J. P. Tresca J. L. Fourrey J. Polonsky and E. Wenkert Tetrahedron Letters 1973 895. Terpenoids and Steroids ,,, (57) CN BF3 ' d A ' CO,H (59) acid.58 Two syntheses of trachylobane are reported.59 Conversion of the mesylate (60) into the ketone (61) and the alcohol (62) by treatment with one equivalent of methylsulphinyl carbanion in DMSO is a key step.59b A model stereospecific synthesis of the A and B rings of gibberellic acid involves the intramolecular Diels-Alder reaction of the acetylenic diene (63).60 An improved procedure is (60) (63) reported for the intramolecular keto-carbene addition to double bonds leading to the bicyclo[3,2,1]octanones.6' This reaction is also employed in the synthesis of (+)-kaurene and (+)-phyllocladene from (-)-abietic acid.62 A synthesis of miltirone is reported.63 58 W.S. Hancock L. N. Mander and R. A. Massey-Westropp J. Org. Chem. 1973 38 4090. 59 (a) R. B. Kelly J. Eber and H.-K. Hung Cunad. J. Chem. 1973 51 2534; (b) R. B. Kelly J.Eber and H.-K. Hung J.C.S. Chem. Comm. 1973 689. 6o E. J. Corey and R. L. Danheiser Tetrahedron Letters 1973 4477. 6' U. R. Ghatak P. C. Chakraborti B. C. Ranu and B. Sanyal J.C.S. Chem. Comm. 1973 548. 62 A. Tahara M. Shimagaki S. Ohara T. Nakata and R. Kenkyusho Tetrahedron Letters 1973. 1701. " D. Nasipuri and A. K. Mitra J.C.S. Perkin I 1973 285. B. A. Marples Concinndiol (64),which was isolated from the red alga Laurencia concinna is only the second example of a natural bromine-containing diterpen~id.~~ The first of this kind was isolated from a sea hare thus providing further support for the suggestion that the sea hares are capable of concentrating the halogen- containing compounds present in their diet." Cyathin B and Cyathin C are further examples of the diterpenoid class first reported last year from Cyathus l~elenae.~~ Several compounds with novel carbon skeletons include leucothol B (65)66and leucothol D,66stemodin (66)67and ~temodinone,~~ which resemble aphidocolin and pachydictyol A (68).68The latter may be derived from geranyl- geranyl pyrophosphate (67) as shown or from farnesyl pyrophosphate followed by isoprenylation.The full report of tle isolation of cembrene-A and the related mukulol from Cornrniphora rnukul is now a~ailable.~~" Cembrene-A is identical with the termite trail pheromone named ne0~embrene-A.~~~ Borjatriol (69) is the first example of a diterpenoid from the Sideritis genera with the normal steroidal A/B-trans ring j~nction.~' 64 J.J. Sims G. H. Y. Lin R. M. Wing and W. Fenical J.C.S. Chem. Comm. 1973 470. 65 W. A. Ayer and L. L. Carstens Canad. J. Chem. 1973,51 3157. 66 H. Hikino S. Koriyama and T. Takemoto Tetrahedron 1973 29 773. 67 P. S. Manchand J. D. White H. Wright and J. Clardy J. Amer. Chem. SOC.,1973 95 2705. 68 D. R. Hirschfield W. Fenical G. H. Y. Lin R. M. Wing P. Radlick and J. J. Sims J. Amer. Chem. SOC.,1973 95 4049. 69 (a) V. D. Patil U. R. Nayak and S. Dev Tetrahedron 1973 29 341; (6) cf. Ann. Reports (B) 1972 69 520. 'O B. Rodriguez and S. Valverde Terrahedron 1973. 29. 2837. Terpenoids and Steroids H 5 Sesterterpenoids Deoxoscalarin (70) a relative of cheilanthatriol and scalarin has been isolated from Spongia q$cinalis. 71 Variabilin is a further linear furanosesterterpene from Ircinia variabili~.~’ 6 Triterpenoids The structure of dendropanoxide (71) has been ~larified,’~‘’ and shown to be similar to that of baccharis It has been suggested that the configuration at C-16 in certain oleane-16a,28-diols should be amended owing to their ready OH HH formation of acetonides.74 However under the reaction conditions employed more recent work shows that both 16a,28- and 16B-28-diols are capable of acetonide formation.” The driving force for the necessary distortion of the D-ring appears to be the interaction between the 16a-hydroxy-group and the l4a-methyl group and the 2la-hydrogen. Corrected structures are presented for faradiol and arnidiol. 76 The ready acid-catalysed rearrangement of the side chain of the 3,23-dihydroxylanosta-8,24-diene(72) to the 25-substituted-A’ 3-compounds suggests that similar rearranged compounds previously isolated in 71 G.Cimino S. de Stafano and L. Minale Experientia 1973 29 934. 72 D. J. Faulkner Tetrahedron Letters 1973 3821. 73 (a)J. D. White J. Fayos and J. Clardy J.C.S. Chem. Comm. 1973 357; (b)cf. Ann. Reports (B) 1972 69 521. 74 R. Segal and A. Taube Tetrahedron 1973 29 675. 75 J. St. Pyrek J.C.S. Chem. Comm. 1973 787. 76 J. St. Pyrek and E. Baranowska Tetrahedron Letters 1973 809. 560 B. A. Marples (72) nature may be artefact^.'^ The (S)-configuration at C-24 is established for the 24,25-epoxytriterpene aglaicol and suggests that it may arise from the cyclization of (3S,22S)-22,23-diepoxy-squalene.The (R)-configuration is reported for each 78 of the cyclopropane ring carbons of presqualene An improved route to A2-triterpenes is available through nickel boride- desulphurization of A2-3-thiobenzyl ethers." An improved synthesis of 32-oxygenated lanostanes involves the formation of the 32-nitrate ester by irradiation of the 7a-nitrite in the presence of oxygen.81 A route to the highly functionalised side chain of some cucurbitacins is described.82 The total synthesis of pyrangolensolide (73) a close relative of fraxinellone is reported.83 An interesting preparation of B-amyrin by the enzymic cyclization of the bicyclic epoxide (74) is reported.8" Somewhat different results were obtained (73) (74) from a chemical cyclization last year.84b A radical induced biogenetic-type cyclization of the aromatic substrate (75) leads to the tetracyclic compound (76).8s A stereospecific synthesis of (+)-taondiol methyl ether (78; R = Me)86" is reported from the epoxide (77).86b 77 N.Entwistle and A. D. Pratt J.C.S. Perkin. I 1973 1235. 78 R. B. Boar and K. Damps J.C.S. Chem. Comm. 1973 11 5. 7v G. Popjak J. Edmond and S.-M. Wong J. Amer. Chem. SOC.,1973 95 2713. R. B. Boar D. W. Hawkins J. F. McGhie and D. H. R. Barton J.C.S. Perkin I 1973,654. J. Allen R. B. Boar J. F. McGhie and D. H. R. Barton J.C.S. Perkin I 1973 2402. 82 F. de Reinach-Hirtzbach and G. Ourisson Tetrahedron Letters 1973 1363. 83 Y. Fukuyama and T. Tokoroyama Tetrahedron Letters 1973 4869.'' (a) H. Horan J. P. McCormick and D. Arigoni J.C.S. Chem. Cumm. 1973 73; (b) c.f.Ann. Reports (B) 1972 69 523. *' J. Y. Lallem M. Julia and D. Mansuy Tetrahedron Letters 1973 4461. (a) A. G. Gonzalez J. Darias J. D. Martin and C. Pascual Tetrahedron 1973. 29 1605; (h) A. G. Gonzalez J. D. Martin and M. L. Rodriguez Tetrahedron Letters 1973. 3657. Terpenoidsand Steroids 561 (75) (76) Treatment of taondiol (78; R = H) with methanolic potassium hydroxide leads to the epimeric compound (79).8 A free-radical mechanism involving an intermediate p-quinone is proposed. Partial backbone rearrangement of the friedelenone (80) gave (inter ah) the As-compound (81).88 It appears that neither contraction of ring A nor expansion of ring D changes the course of backbone rearrangement in the euphol series8’ The acid-catalysed rearrange- ment of the dienone (82) to the phenol (83) involves an initial methyl shift to the oxygen-bearing carbon followed by a second shift to C-2.” Further base- induced fragmentations of some swietenine derivatives show the critical depen- dence of the reaction course on substit~tion.~’ The 23-oxygenated lactone (84) is reported in a sea c~cumber.’~ Glabretal (85)is one of several compounds of a new skeletal class which may arise by capture ” A.G. Gonzalez M. A. Alvarez J. Darias and J. D. Martin J.C.S. Perkin I 1973 2637. *’ T. Kikuchi M. Niwa M. Takayama T. Yokoi and T. Shingu Tetrahedron Letters 1973 1987. 89 J. L. Zundei G. Wolff and G. Ourisson Bull.SOC.chim. France 1973 3206. O0 J. R. Bull and A. J. Hodgkinson Terrahedron 1973 29 1109. ’’ J. D. Connolly R. Henderson R. McCrindle K. H. Overton and N. S. Bhacca J.C.S. Perkin I 1973 865. 92 I. Rothberg B. M. Tursch and C. Djerassi J. Org. Chem.. 1973 38 209. 562 B. A. Marples HOy$ 'OAc of the 13-methyl group by a C-14 carbonium ion in a step subsequent to the tirucallol to apotirucallol-type of rearrangement.93 Cyclofuntumienol (86)94u and cyclotrichosantol (87)94bare new isomeric 3 1-nortriterpenes. Botryococcene 9J G. Ferguson P. A. Gunn W. C. Marsh R. McCrindle R. Restivo J. D. Connolly J. W. B. Fulke and M. S. Henderson J.C.S. Chem. Comm. 1973 159. 94 (a) L. Mukam G. Charles J. Hentchoya Th. Njimi and G. Ourisson Tetrahedron Letters 1973 2779; (6)M.KoCor and J. St. Pyrek J. Org. Chem. 1973 38 3688. Terpenoitis and Steroids (88)is a major metabolite of the alga Botryococcus br~unii.~' A number of quinone methides related to pristimerin are reported.96 Tingenone (89) maitenin and tingenin A all have the same struct~re.~~'~~*~ The other compounds reported are 20-hydro~ytingenone,~~" tingenin B,96cand disperm~quinone.~~~ 7 Steroids The chemistry and biology of ~aponins,~' and microbiological hydro~ylation,~~ steroid acids in petroleum99 are reviewed. The contaminent in ergosterol 5a,8a-peroxide which was claimed to be the epimeric 5/?,8/?-peroxide is now shown to be 9,ll-dehydroergosterol peroxide."' The 12a- and 12~-mesylates (90) are converted into the c-nor-D-homo- compounds (cholajervanes) (91) and (92).Acetolysis of the D-homo-compound 95 R.E.Cox A. L. Burlingame D. M. Wilson G. Eglinton and J. R. Maxwell J.C.S. Chem. Comm. 1973,284. 96 (a) P. M. Brown M. Moir R. H.Thomson T. J. King V. Krishnamoorthy and T. R. Seshadri J.C.S. Perkin I 1973 2721 ;(b) F. D. Monache G. B. M. Bettblo 0. G. de Lima 1. L. d'Alberquerque and J. S. de B. Cdlho ibid. p. 2725; (c) K. Nakanishi V. P. Gullo I. Miura T. R. Govindachari and N. Viswanathan J. Amer. Chem. SOC.,1973 95 6473; (d)J. D. Martin Tetrahedron 1973 29 2997. '' R. Tschesche and G. Wulff Fortschr. Chem. org. Nutursroffe 1973 30 462. 98 E. R. H. Jones Pure Appl. Chem. 1973 33 39. 99 W. K. Seifert Pure Appl. Chem. 1973 34 633. loo M. H. Fisch R.Ernst B.H.Flick J. Arditti D. H. R. Barton P. D. Magnus and I. D. Menzies J.C.S. Chem. Comm. 1973 530. lo' R. C. Ebersole and F. C. Chang J. Org. Chem. 1973 38 2579. 564 B. A. Marples (93) is accompanied by inversion at C-13 and the 13a,l7aa-acetate (94) is a product.'02 A similar result is obtained in the formolysis of the D-homotosylate (95) which leads in part to the 13a-17aa-formyl-l7~-methyl compound (96).'03 Treatment of 5a-and 5P-pregnane-3,20-dione with HF-SbF gives the corres- ponding 13a,l7/3-isomer as the major product.' O4 Oestrone is converted by HF-SbF into 9,ll-dehydro-oestrone via a C-9 carbonium ion. The phenol- dienone rearrangement product oestra-4,9-diene-3,17-dione,' O5 is a minor product. The previously reported rearrangement of (19R)- 19-hydroxy- 19- methyl-3-oxo-5a-steroids into 3a-hydroxy- 19-methyl- 19-0x0-%steroids has been shown by 'H-labelling studies to involve an intramolecular hydride transfer.lo6 The iodo-aldehyde (97) is converted into the cyclic ether (98) by an alumina- induced cyclization accompanied by a hydride shift from the solvent (hexane). lo' OAc H (94) (93) OTs P H H (96) (95) Treatment of the ene reaction product (99) with lithium aluminium hydride remarkably gave the A-ring aromatized compound ( 100).'08 Neighbouring group participation by a 7a-hydroxy-group accelerates the nucleophilic opening of 4a,5a-epoxides. 'O9 Direct P-epoxidation of cholesterol is preponderant using hydrogen peroxide and ferric acetylacetonate in aceto- nitrile.' lo Further studies on long-range substituent effects are reported." ' Io2 I.Khattak D. N. Kirk C. M. Peach and M. A. Wilson J.C.S. Chem. Comm. 1973 341. Io3 F. B. Hirschmann and H. Hirschmann J. Org. Chem. 1973 38 1270. Io4 J.-C. Jacquesy R. Jacquesy S. Moreau and J.-F. Patoiseau J.C.S. Chem. Comm. 1973 785. Io5 J. P. Gesson J.-C. Jacquesy and R. Jacquesy Brtll. SOC. chim. France 1973 1433. Io6 J. Wicha and E. Caspi J. Org. Chem. 1973 38 1280. lo' H. Suginome and K. Kato Tetrahedron Letters 1973 4143. lo8 H. de Nijs and W. N. Speckamp Tetrahedron Letters 1973 3631. lo9 D. H. R. Barton and Y. Houminer J.C.S. Chem. Comm. 1973 839. I lo M. Tohma T. Tomita and M. Kimura Tetrahedron Letters 1973 4359. 'I' (a) I.G. Guest and B. A. Marples J.C.S. Perkin I 1973 900; (6) V. V. Egorova A. V. Zakharychev and S. N. Ananchenko Tetrahedron 1973,29,301; (c) G. C.Wolf E. L. Foster and R. T. Blickenstaff J. Org. Chem. 1973,38 1276; (6)J. B. Jones and P. Price Tetrahedron 1973 29 1941. Terpenoids and Steroids 17 4 H Evidence is presented in favour of inductive,' 'layb conformational,' 'lb and steric effects.' 'Ic However variation of C-17-substituents does not appear to affect the course of homologations of 3-0x0-5a-steroids.' 'Id The addition of hypobromous acid to A4-steroids gives a significant quantity of 4P-bromo-5a-hydroxy-compound in contrast to similar reactions with A'-steroids.' Func-tionalization of 17a-methylsteroids is readily achieved by photolysis of the 12a-nitrite esters or by reaction of the 12a-hydroxy-compounds with lead tetra- acetate.' l3 Epoxidation of the 9,lO-double bond of Westphalen's diol derivatives provides improved yields in the similar functionalization of the 5P-methyl group.' l4 Mercuric acetate oxidation of a A14-steroid provides the A8(14)-1 5-0x0- compound.' ' ' The interest in biogenetic-type synthesis of tetracyclic compounds continues." 6*1l7 Syntheses of progesterone' '6a,b and oestrone' 16' by this means are reported. Cyclization of the acetylenic alcohol (101) in 2-nitropropane affords a route to 17-oxygenated pregnanes as the intermediate C-20-vinyl cation is trapped by the solvent and leads to the oximino-ether (102).'16d3e Evidence for some degree of concertedness in these cyclizations is provided by a study of the aromatic substrates (103) in which the reaction rate is dependent on substituents in the aromatic ring and the ortho to para product ratio is dependent on the nature of the leaving group (OR2).''' ' '' P.Morand and A. Polakova-Paquet Canad. J. Chem. 1973 51 4098. 'I3 Ch. R. Engel D. Mukherjee and G. J. Beaudoin Sreroids 1973 21 857. J. G. L1.Jones and B. A. Marples J.C.S. Perkin I 1973 1143. 'I5 E. C. Blossey and P. Kucinski J.C.S. Chem. Comm. 1973 56. 'I6 (a)R. L. Markezich W. E. Willy B. E. McCarry and W. S. Johnson J. Amer. Chem. SOC.,1973 95 4414; (6)B. E. McCarry R. L. Markezich and W. S. Johnson ibid. p. 4416; (c) P. A. Bartlett and W. S. Johnson ibid. p. 7501 ;(4D. R. Morton M.B. Gravestock R. J. Parry and W. S. Johnson ibid. p. 4417; (e)D. R. Morton and W. S. Johnson ibid. p. 4419. 'I7 P. A. Bartlett J. I. Braceman W. S. Johnson and R. A. Volkmann J. Amer. Chem. Soc. 1973 95 7502. 566 B. A. Marples Poriferasterol and stigmasterol may be synthesized from the (22R)- and (22s)- allylic alcohols (104) respectively.' l8 A Claisen rearrangement allows the stereospecific introduction of the 24-ethyl group. Lithium-ammonia reduction of A8~'4~-7-oxo-compounds provides a route to the unnatural 14/3-steroids.l OH Reduction of 14-dehydro-8,19-epoxy-compounds with zinc-acetic acid exclu- sively provides the 14-dehydro-l9-hydroxy-8/3-compounds.'Syntheses of 9a-2o and 9fi-methyl-19-norsteroidsare reported.' Resibufogenin is readily converted by acid treatment into 14a-and 14/3-arteb~fogenin.'*~ Direct conversion of 14-dehydrobufalin into bufalin employs the direct reaction of the 14,15-d0uble bond with hypohalous acid rather than proceeding through the epoxide resi- bufogenin.' 23 An improved procedure for sulphur dehydrogenation of the 'I8 W.Sucrow P. P. Caldeira and M. Slopianka Chem. Ber. 1973 106 2236. I l9 I. Midgley and C. Djerassi J.C.S. Perkin I. 1973. 155. G. Kruger and G. I. Birnbaum Tetrahedron Lerrers 1973 501. R. V. Coombs,J. Koletar R. Danna H. Mah and E. Galantay J.C.S. Perkin I 1973 2095. "* Y. Kamano and G. R. Pettit Canad. J. Chem. 1973,51 1973. Y. Kamano and G. R. Pettit J. Org. Chem. 1973.38 2202. Terpenoids and Steroids lactone ring is used in a synthesis of re~ibuf0genin.l~~ The conversion of the starfish aglycone (105) into A9(' ')-progesterone provides a synthesis of cortico-steroids from marine sources.125 Interest has focused on the partial'26 and tota112' synthesis of la-hydroxy- cholecalciferol which exhibits potent antirachitic activity.The partial syntheses proceed through the irradiation of la,3~dihydroxycholesta-5,7-diene or its esters whereas the total synthesis employs the combination of the acetylenic ditrimethylsilyl ether (106) with the appropriate cD-fragment as a key step. OSiMe HO * A synthesis of (22s)-hydroxyvitamin D4is also reported but this compound has no significant antirachitic activity.' 28 The structures of the marine sterols 24,28-didehydroaplysteroland aplysterol are supported by synthesis of the former and the X-ray crystal structure of the latter.' 29 The principal aglycones from the saponins of the starfish Marthasterias glacialis are the unusual natural 23-0x0-cholestanes (107) and (108).' 30 The W.Haede W. Fritsch K. Radscheit and U. Stache Annalen 1973 5. lZ5 J. E. Gurst Y. M. Sheikh and C. Djerassi J. Amer. Chem. SOC.,1973 M,628. (a) D. H. R. Barton R. H. Hesse M. M. Pechet and E. Rizzardo J. Amer. Chem. Soc. 1973 95 2748; (b) A. Furst L.Labler W. Meier and K. H. Pfoertner Helu. Chim. Acra 1973 56 1708; (c) C. Kaneko S.Yamada A. Sugimoto M.Ishikawa ' S.Sasaki and T. Suda Tetrahedron Letters 1973 2339. R. G. Harrison B. Lythgoe and P. W. Wright Tetrahedron Letters 1973 3649.lZ8 D. R. Crump D. H. Williams and B. Pelc J.C.S. Perkin I 1973 2731. lZ9 (a) P. De Luca M. De Rosa L. Minale R. Puliti G. Sodano F. Giordano and L. Mazzarella J.C.S. Chem. Comm. 1973 825; (b) cf. Ann. Reports (B) 1972 69 529. IJoD. S. H. Smith A. B. Turner and A. M. Mackie J.C.S. Perkin I 1973 1745. 568 B. A. Marples related 6'-deoxyglucoside (109) is also reported in Acasthaster planci,' 31 and the 3-sulphate of compound (105) is reported in asterosaponin New phytoecdysones include calonysterone (1 lo),'33 the related kaladsterone (1 1 l),' 34 and dacrysterone. '35 The synthesis of 16-oxopregnanes is achieved by microbiological oxidation of diosgenone. 36 Microbiological dehydrogenation of 5P-androstane-3,17-dione at C-1 C-2 and C-4,C-5 involves the stereospecific removal of the 21-and the 4a-hydrogens.' 37 A number of studies are reported on the microbiological hydroxylation of androstanes,' 38a*b7c oestranes,' 38a and pregnanes'38" with I 0-~-~-6'-deoxyglucosyl ( 109) OH I3l Y.M. Sheikh and C. Djerassi Tetrahedron Letters 1973 2927. 13' (a) S. Ikegami Y. Kamiya and S. Tamura Tetrahedron Letters 1973 731; (6)S. Ikegami Y.Kamiya and S. Tamura Tetrahedron 1973 29 1807. '33 L. Canonica B. Danieli G. Ferrari J. Krepinsky and G. Rainoldi J.C.S. Chem. Comm. 1973 737. '34 L. Canonica B. Danieli G. Ferrari M. A. Haimova and J. Krepinsky Experientia 1973 29 1062. 135 G. B. Russell and J. G. Fraser Austral. J. Chem. 1973 26 1805. 136 E. Kondo and T. Mitsugi Tetrahedron 1973 29 823.13' S. Ikegawa and T. Nambara Chem. and Ind. 1973 230. IJ8(a) J. W. Browne W. A. Denny Sir E. R. H. Jones G. D. Meakins Y. Morisawa A. Pendlebury and J. Pragnell J.C.S. Perkin I 1973 1493; (b) V. E. M. Chambers W. A. Denny J. M. Evans Sir E. R.H. Jones A. Kasal G. D. Meakins and J. Pragnell ibid. p. 1500; (c) A. M. Bell I. M. Clark W. A. Denny Sir E. R. H. Jones G. D. Meakins W. E. Miiller and E. E. Richards ibid. p. 2131 ;(4A. S. Clegg W. A. Denny Sir E. R. H. Jones G. D. Meakins and J. T. Pinhey ibid. p. 2137. Terpenoids and Steroids OH Rhizopus and Aspergillus strains. Microbiological oxygenation of B-norsteroids with Rhizopus nigricans and Absidia orchidis is also re~0rted.I~’ lJ9 J. Joska 2. Prochazka J. Fajkos and F.Sorm CON.Czech. Chem. Comm. 1973 38 1398.