1977 2317Terpenoids. Part 7.l Diequatorial Opening of 2,3-Epoxides of ent-Kauranes and ent-GibberellanesBy Martin W. Lunnon and Jake MacMillan," School of Chemistry, The University, Bristol BS8 I T SReduction of ent-2a,3cc-epoxykaur-l6-en-19-01 (1 ) by hydride to the 2-equatorial alcohol (4) is attributed to par-ticipation by the 19-hydroxy-group. since the 19-tetrahydropyranyl ether (2) and the 4.4-dimethyl epoxide (24) arereduced normally to the corresponding 3-axial alcohols (7) and (26) respectively.Reduction of ent-2~,3~-epoxykaur-16-en-19-01 (1 3) and the 19-tetrahydropyranyl ether (1 4) by hydride gavethe 3-equatorial alcohol (1 9) and the 1 9-tetrahydropyranyl ether (23) respectively. Analogously, acidic hydro-lysis of the ent-2P.3P-epoxides (30) and (31) in the ent-kaurane series, and of (40) and (41) in the enr-gibberellane series, afforded the diequatorial 2.3-diols.The abnormal opening of these ent-2P,3p-epoxides isattributed to the steric effect of the adjacent ent-4a-methyl group.REQUIRING ent-2~hydroxykaurenes for microbiological ent-Za,3a-epoxide (1) , as originally reported by Bakkerconversion into ent-2a-hydro~ygibberellanes,~ we have et al. ,4 gave the ent-2a(eq)-alcohol (4) and the ent-3a(ax)-followed up the report by Bakker et aZ.4 that ent-2a,3u- alcohol (6) in the ratio 3 : 2. However reduction of theepoxykaur-16-en-19-01 (1) was reduced by lithium 19-tetrahydropyranyl (Thp) ether (2) yielded only thealuminium hydride to the ent-2a-equatorial alcohol (4) normal ent-3a(ax)-alcohol (7). This result suggests thatas well as the expected ent-3a-axial alcohol (6). In con-firming this result we have encountered other examplesof the diequatorial opening of 2,3-epoxides of bothent-kauranes and ent-gibberellanes. These exceptionsto the normal diaxial cleavage of epoxycyclohexanes arediscussed in this paper.Reductioiz by Hydride.-Bakker et aZ.4 prepared theent-Zcq3a-epoxide (1) from the diepoxide (8), which theyobtained as the sole product of the reaction of the dienol(10) with 3-chloroperbenzoic acid.In our hands andunder similar conditions, the dienol (10) gave equalamounts of the diepoxides (8) and (12). In their n.m.r.@ H2l8 19'CH2R H o q l CHzR H O G 1 CH2R@compounds ent-2a,3a-epoxides described (1) and by (8) Bakker which et corresponded aZ.4 only the to the 18- @ CH2 gl10 0( 4 ) R = OH( 5 ) R =OThp( 6 ) R =OH( 7 ) R =OThp(,) = OH( 2 ) =OThp(3) R = Hspectra 17-protons both and epoxides are assumed had the to same be ent-16p,l7p-epoxides, chemical shift for the0 formed by attack from the less hindered face.5 The2,3-stereochemistries of the diepoxides (8) and (12), andof the monoepoxides (1) and (13) derived from them byfrom the chemical shifts of the 18- and 20-protons.Inthe less polar ent-2p,3p-diepoxide (12) and the corres-methyl groups were deshielded (ca. 1.3 p.p.m.), ascompared with those of ent-kaurenol (15). In the reatment with potassium seleno~yanide,~.~ were assigned CH2R CH*R( 8 ) R =OH( 9 ) R = H(10) R =OH( 1 1 ) R = H ponding monoepoxide (13), both the C-4 and C-10protons were deshielded (ca.1.3 p.p.m.). These stereo- 0:: 0:;chemical assignments were confirmed (see later) by theproducts obtained from reduction of the monoepoxidesby hydride and by an alternative synthesis (see later) ofthe nor-ketone (30) corresponding to the ent-2@,3p- (12) (13) R =OH (15)epoxide (13). Formation of the ent-2p,3p-epoxide by (14) R=OThpattack from the more hindered face of the dienol (10) isprobably due to participation by the 19-hydroxy-group.epoxides (I) and (13) were reduced anomalously. s' HCH2.OH 'CH2R CH2.0Hthe anomalous reduction of the ent-2a,3a-epoxide (1) wascaused by participation of the 19-hydroxy-group, With lit 'Iiun1 hydride both the directing elzt-3p-hydride attack, perhaps through theThePart 6, U.H. Bowen, C. Cloke, and J , MacMillan, J.C.S.M. W. Lunnon, J. MacMillan, and B. 0. Phinney, J . C . S .L. J . Heeley and J. MacMillan, J.C.S. Perkin I , 1976, 1022.H. J. Bakker, I. F. Cook, P. R. Jefferies, and J. R. Knox,J . R. Hanson, J . Chem. SOC., 1963, 5061.C. C. J . Culvenor, Austral. J . Chem., 1964, 17, 233.H. B. Henbest and R. A. L. Wilson, J . Chem. SOC., 1957,Tetrahedron, 1974, 30, 3631.Perkin I , 1976, 378.Perkin I , preceding paper.195823 18 J.C.S. Perkin Icomplex (16). Ghisalberti et aZ.s also observed par-ticipation of the 19-hydroxy-group in the reaction of the19-acetate of this epoxide with base, resulting in theformation of the oxetan (17).However, although re-duction of the 19-Thp ether (2) gave only the 3-axialalcohol (7), the Thp group introduces a possible stericbarrier to ent-3p-hydride attack. To interpret theabnormal reduction of (1) solely in terms of the directingeffect of the 19-hydroxy-group, replacement of thehydroxy-group by hydrogen was undertaken : the 4,4-dimethyl epoxide (3) was prepared via the ent-3~-alcohol(22) and the diene (11).have reduced the monoto-sylate (20) with lithium aluminium hydride to give thegem-dimethyl compound (22) and the oxetan (18) in theratio 1 : 3. In the present work the 19-fi-bromo-benzenesulphonate (2 1) was available from anotherproject. Reduction of it with lithium aluminiumhydride in refluxing tetrahydrofuran gave equal amountsof the required gern-dimethyl compound (22) and, sur-prisingly, ent-kaur-16-en-19-01 (15), but the mixture couldnot be separated.The latter compound was not formedat room temperature, when the main products were theJefferies and Retallack( 1 8 ) R = H (20) R = O T s(21) R =OBs(22) R = H(23) R = OThp(25)(26)(27) R =OH(28) R =OThpdiol (19) and the required gem-dimethyl compound (22) ;the yields were variable and small amounts of the oxetan(18) were sometimes formed but compound (22) wasalways the major product. The formation of ent-kaur-8 E. L. Ghisalberti, P. R. Jefferies, and J . R. Knox, Austval. j.Chewz., 1969, 22, 456.16-en-19-01 (15) at the higher temperature of reductionis probably due to reduction of the intermediate oxetan(18), since the latter, prepared by the action of base onthe $-bromobenzenesulphonate (21), gave ent-kaur-16-en-19-01 (15) and the gem-dimethyl compound in theratio 3 : 1 under the same conditions of reduction.The next step, dehydration of the alcohol (22) wasexpected to occur smoothly with phosphoryl chloridesince Ghisalberti et aL8 found that the diene (11) was thesole product from this reaction. However, in our handsa mixture was obtained and shown by g.1.c.-massspectrometry to contain one major, and four minor,isomeric products each with M+ 270 as expected for thediene (11).Although the mixture could be resolved byanalytical t .l.c. on silica gel-silver nitrate layers,preparative t.1.c. under these conditions was unsuccessful.The total product was therefore treated with 3-chloro-perbenzoic acid to give one major product, which wasseparated from several minor products by layer chro-matography and assigned the structure (24) from thefollowing n.m.r.data. In addition to the 2- and 3-epoxide protons at 6 2.81 (d, J 4 Hz) and 3.22 (dd,J 4 and 6 Hz), respectively, the n.m.r. spectrum containedan AB system at 6 3.76 and 4.06 ( J 13 Hz), typical ofhydroxymethylene protons, and a one-proton singlet at6 2.93 in the epoxide region. Formation of the di-epoxide (24) from the diene (11) was repeatable and canbe explained by rearrangement of the expected di-epoxide (9) to the allylic alcohol (25) followed by furtherepoxidation of the 15,16-double bond.I t is significantthat epoxidation of the 2,3-double bond in the diene (11)gave no ent-2P,3p-epoxide, thereby supporting thesuggestion that ent-2P,3p-epoxidation of the dienol (10)occurred by participation of the 19-hydroxy-group.Reduction of the diepoxide (24) with lithium alu-minium hydride gave only one product (g.1.c.-massspectrometry), which formed a bistrimethylsilyl etherand was assigned the structure (26). The n.m.r.spectrum showed that the 15,16-epoxide and the 17-hydroxy-group of the parent compound were stillpresent, and that the 2- and 3-protons of the 2,3-epoxide had been replaced by an ent-3P-proton with6 3.42 and WB 7 Hz. Thus the en.t-2~,3a-epoxide (24)without oxygenation at C-19 was reduced normally tothe ent-3a(ax)-alcohol, supporting the view that abnormalreduction of the ent-2~,3a-epoxide (1) is due to par-ticipation of the 19-hydroxy-group.In the reduction of the ent-2pJ3p-epoxide (13) the19-hydroxy-group was not expected to direct hydrideattack, yet reduction of this epoxide with lithiumaluminium hydride also gave a mixture of the ent-3p(eq)-alcohol (19) and the ent-2p-alcohol (27) in theratio 3 : 2.This ratio was not substantially altered inthe reduction of the 19-Thp ether (14), thereby excludingan explanation for the anomalous reduction based uponthe electrophilicity of an aluminium complex with theP. R. Jefferies and R. W. Ketallack, Austral. J . Chrn., 1968,21, 13111977 231919-hydroxy-group.1° Although it is possible that theanomalous reduction of the 19-Thp ether is due to thecomplexing of the Thp ether oxygen atoms and the ent-2p,3p-epoxide system with the aluminium, the simplestexplanation of these results is that ent-3a-attack of( 2 9 ) (30) R =OH(31) R = H(32) R = OH (34) R' = Me, R2= CHz-OH(35) R ' = R2= C02Me(36) R ' = R2=Me(37) R =OH(33) R = H (38) R = H( 4 0 )(39)hydride is sufficiently hindered by the ent-4a-methylgroup for attack at the ent-2a-position to occur also.Support for this view was obtained from a study of acid-catalysed opening (see later) and from the reduction ofthe ent-2p,3p-epoxide (13) with dissolving metal wherethe sterically undemanding solvated electrons areknown l1 to reduce sterically hindered epoxides to axialalcohols.In two experiments using lithium and hexa-methylphosphoric triamide no ent-3p(eq)-alcohol (19)was detected.In one reduction, the 2-axial alcohol (27)and its endocyclic double bond isomer were the soleproducts; in the other the 2-axial alcohols were accom-panied by some of the olefin (lo), for which there isprecedent ,12Acid-catalysed Opening.-Attention was next directedto the acid-catalysed opening of these 2,3-epoxides. Toavoid the complication of acid-catalysed endomerisationof the 16-ene to the 15-ene, the nor-ketones (29) and (30)were prepared by oxidation of the corresponding ent-2a,3a- and 2p,3@-epoxides (1) and (13) with osmiumt et raoxide -periodat e. The ertt-2 p, 3 P-epoxy-ket one (30)was also prepared by the methods described by Beeleyand MacMillan from the nor-ketone (32) via the bromo-lo E.Glotter, S. Greenfield, and D. Lavje, Tetrahedmn Letters,1967, 5261.hydrin acetate (34). This preparation confirmed theent-2p,3p-stereochemistry of the nor-ketone (30) andthereby the 2,3-stereochemistry of all ent-2,3-epoxy-kauranes described in this paper.Reaction of the ent-2@,3p-epoxy-ketone (30) withM-sulphuric acid in tetrahydrofuran at room tem-perature gave one product, shown to be a triol byformation of a tristrimethylsilyl ether and recognisedas the 2,3-diequatorial compound (37) from thevalue of 10 Hz and the large W , value of ca. 27 Hz forthe 2-proton. Treatment of the ent-2~,3a-epoxy-ketone (29) under the same conditions gave a singletriol, which had different mass and n.m.r.spectra fromthe triol (37) and is therefore formulated as the 2,3-diaxial compound (39). The signals for the equatoriallyrelated 2- and 3-protons were obscured in the n.m.r.spectrum by the 19-proton signals, and J2,3 could notbe determined.have noted the anomalousopening of the ent-2p,3p-epoxide (40) of a C,, gibberellinto give both 2,3-diequatorial and -diaxial diols. Toprovide an example of the ent-gibberellanes without the19,lO-lactone system, acid-catalysed opening of theent-2p,3p-epoxide (41) of a C2, gibberellin was examined.The required epoxide (41) was prepared by treatment ofthe known3 bromohydrin (35) with base. A minorproduct was a lactone characterised as (42) or (43) byspectroscopic data, but no attempt was made to distin-guish between these alternatives.Treatment of theepoxide (41) with M-sulphuric acid gave only the di-equatorial diol (44), characterised by the 1 2 . 3 value of10 Hz with a W1 value for the 2-proton of ca. 26 Hz.Beeley and MacMillanC02Me0::BrC02Me C02MeMe02C(44) (45)Thus diequatorial opening of the three ent-2p,3P-epoxides (30), (40), and (41) was observed on treatmentwith M-sulphuric acid. These epoxides contain varyingdegrees of oxygenation at C-19, and -10 or -20 whichcould assist the development of a positive charge atl1 A. S. Hallsworth and H. B. Henbest, J . Chem. SOC., 1957,l 2 A. S. Hallsworth and H. R. Henbest, J . Chem. SOC., 1960,4604.35712320 J.C.S. Perkin IC-2 from the protonated epoxides and cause ent-2a-attack of water.To test this possibility the ent-2p,3p-epoxide (31), lacking any other oxygenation inring A, was examined. This epoxide (31) was preparedfrom the alcohol (22), which was converted into thecorresponding 17-nor-ketone. The latter, in contrastto its parent (22), was smoothly converted into theolefin (33) with phosphoryl chloride. Reaction of thisolefin with bromine acetate gave the bromohydrin (36),which with base gave the epoxide (31). Acidic hydro-lysis of this ent-2p,3P-epoxide (31) gave entirely theabnormal diequatorial diol (38) with J2.3 10 Hz and Wifor the 2-proton 26 Hz. Thus the diequatorial openingof the ent-2p,3p-epoxides (30), (31), (40), and (41) isindependent of oxygenation at C-10, -19, and -20.Precedents for the anomalous opening of epoxideswith acids and hydride in the absence of participatinggroups have been described by Barton et aL.13 Theyfound that the 2p,3p-epoxides of lanostane and lanost-8-ene weie reduced by lithium aluminium hydride to theequatorial 3P-alcohols and were opened by hydrobromicacid to the 2a-bromo-3p-alcohols.Barton et aZ.12suggested that these 2p,3p-epoxides opened diaxially inthe twist-boat form. However this explanation cannotapply to the ent-2P,3p-epoxide (40) because of theconformational restraint imposed by the lactone bridge.Moreover ent-2a,3or-epoxides open normally, for example(2) or (24) as shown earlier in this paper, 2@,3p-gibberel-lins ,14 and 2 a ,3 a-lanost ane. l3 An alternative explan-ation for these facts is that, in the ent-2p,3p-epoxidesnucleophilic attack at C-3 is hindered by the adjacentent-4a-substituent.Thus nucleophilic attack occurs atC-2 to give diequatorial opening. Consistent with thissuggestion is the fact that the C,, gibberellin epoxide(40) gave a mixture of diequatorial and diaxial diols;here the lactone bridge causes the 4-methyl group to bepulled away from the line of attack at C-3.An attempt was made to exploit the anomalous open-ing of ent-2p,3p-epoxides to prepare an ent-2a-methyl-kaur-16-ene for microbiological transformation studies.However, treatment of the epoxide (13) with niethyl-magnesium iodide in benzene afforded the alcohol (45),presumably by rearrangement of the epoxide followedby further reaction of the resultant aldehyde, and, asa minor product, the alcohol (19).The structure of thealcohol (45) was revealed by the n.m.r. spectrum whichcontained signals for the MeCH(0H) grouping at 6 1.15and 3.67 ( J 6 Hz). The minor product (19) may beformed either by reduction of the epoxide (13) by theGrignard reagent directly or after rearrangement to the3-ketone followed by reduction (cf. ref. 15).EXPERIMENTALFor general experimental details see ref. 16, except fort.l.c., for which we used Merck Kieselgel HI; and for i.r.spectra, which are given for solutions (ca. 40 mg ml-l) inl3 D. H. R. Barton, D. A. Lewis, and J . F. McGhie, J . Chew.Soc., 1957, 2907.l4 J. MacMillan, J . C. Seaton, and P. J . Suter, Tetmhedron,1962, 18, 349.methylene dichloride in 0.2 mm cells.For g.1.c.-massspectrometry of methylated (CH,N,) and trimethyl-silylated samples see ref. 17, except for the g.1.c. columns,which are described in ref. 18.Epoxidation of ent-Kaura-2,lS-dien- 19-01 (10) .-The dienol(10) (710 mg) in chloroform (180 ml) was treated with3-chloroperbenzoic acid (3.36 g) a t 0 "C for 2 days. Themixture was washed with ice-cold aqueous 6 sodiumhydroxide (2 x 100 ml), then with water. Evaporationgave a gum which was separated by multiple-elutionpreparative layer chromatography (p.1.c.) with acetone-n-hexane (3 : 7). Recovery from the band a t lower RFvalue gave ent-2a, 3a: 16(3,17p-diepoxykauran- 19-01 (8) (298mg) , crystallising from benzene-light petroleum as prisms,m.p.171-175" (lit.,4 no m.p. recorded) (Found: C, 75.3;H, 9.9. Calc. for C20H3003: C, 75.4; H, 9.5); v,,,.3 630, 1026, 955, and 833 cm-l; 6 1.04 (s, 20-H,), 1.21 ( s ,18-H3), 2.20 (dd, J 6 and 15 Hz, 1-H), 2.80 and 2.89 (dd,J 5 Hz, 17-H,), 3.24 (m, 2- and 3-H), and 3.64 and 3.90Recovery from the band a t higher R, value gave ent-2p,3P: 16~,17~-diepoxyhauran-19-01 (12) (269 mg), crystal-lising from benzene as cubes, m.p. 175-182' (Found: C,75.5; H, 9.7. C,,H,,O, requires C, 75.4; H, 9.5); vmx.3 620, 1 030, 1 020, 954, and 847 cm-l; 6 1.22 (s, 18- and20-H,), 2.42 (dd, J 15 and 2 Hz, 1-H), 2.80 and 2.89 (JAB5 Hz, 17-H,), 3.00 (d, J 4 Hz, 3-H), 3.30 (m, 2-H), and 3.36and 3.96 (JAB 11 Hz, 19-H,).ent-2a, 3a-Epoxyhaur- 16-en- 19-01 ( 1) .--The diepoxide (8)(294 mg), in methanol (30 ml) containing potassium seleno-cyanate (1.29 g), was refluxed for 5.5 h. The mixture wasconcentrated by distillation, then diluted with water andextracted with ether.The extract gave an oil (317 mg)which was purified by p.1.c. with ethyl acetate-lightpetroleum (3 : 2). Elution of the band at RF 0.4 gave theelzt-2a,3a-monoepoxide (1) ( 189 mg), which crystallised frombenzene-light petroleum as needles, m.p. 158-1 60" (lit.,4153-154") (Found: C, 79.4; H, 9.9. Calc. for C,,H,,O,:C, 79.4; H, 10.Oyo); v,,,. 3 640, 1 660, 880, and 830 cm-l;6 1.02 (s, 20-H,), 1.20 (s, 18-H3), 2.18 (dd, J 6 and 15 Hz,1-H), 2.64br (s, 13-H), 3.26 (m, 2- and 3-H), 3.63 and 3.89( J a ~ 11 Hz, 19-H,), and 4.74br (s) and 4.80br ( s ) (17-H2).ent-2P,3~-E~oxykaur-16-en-19-oZ (13) .-The ent-ZP,3P-di-epoxide (12) (269 mg) was treated with potassium seleno-cyanate (1.22 g) in methanol (30 ml) as for the ent-2a,3a-diepoxide (8).The oily product (270 mg) was purified byp.1.c. in ethyl acetate-light petroleum (3 : 2). Recoveryfrom the band a t RT" 0.7 gave ent-2P,3P-epoxykaur- 1 6-en-19-01 (13) (149 mg), needles, m.p. 118-120" (from benzene-light petroleum) (Found: C, 79.1; H, 10.2. C,,H,,02requires C, 79.4; H, 10.Oyo); vmx. 3 635, 1660, 878, and846 cm-l; 6 1.20 (s, 18- and 20-H,), 2.40 (dd, J 2 and 15 Hz,1-H), 2.66br (WJ 10 Hz, 13-H), 2.97 (d, J 4 Hz, 3-H), 3.30(m, 2-H), 3.33 and 3.95 ( J k n 11 Hz, 19-H,), and 4.74and 4.80 (17-H2).Reductions with Lithium A luminium Hydride.-(a) ent-2a, 3a-Epoxykaur- 1 6-en- 1 9-01 ( 1 ) .The epoxide (1 28 mg) ,lithium aluminium hydride (410 nig), and tetrahydrofuran(4 ml) were heated under reflux for 6 h. To the cooled(dd, J 11 Hz, 19-H,).l5 M. S. Kharasch and S. Weinhouse, J . Org. Chem., 1936, 1,l6 J . MacMiilan and T. J. Simpson, J.C.S. Perkin I, 1973, 1487.l7 J . R. Bearder, J . MacMillan, and B. 0. Phinney, Phyto-M. S. Karasch and S. Weinhouse, J . Org. Chew., 1936,1, 209.209.chemisly-y, 1973, 12, 26551977 2321mixture ethyl acetate was added and the resulting sus-pension was poured into a solution of ammonium chloride(9 g) in water (45 ml). Extraction with ethyl acetateyielded a solid (131 mg), which was separated by p.1.c.inmethanol-chloroform (1 : 19) : Double development andelution of the band at Rp 0.3 gave ent-kaur-l6-ene-2~,19-diol (4) (57 nig), crystallising from ethyl acetate as prisms,m.p. 218-219" (lit.,4 220-221"); urnax. and 6 as previouslyrecorded; 4 ?n/e (for Me,Si derivative) 448 (M+, ,S) 1.68 ((1, J 2 Hz,17-H,) and 5.14 (m, 15-H).G.1.c.-mass spectrometry of thetrimethylsilylated mixture gave : (i) the A15-isonier Me,Siether, shorter tit, m/e 448 ( M i , lye), 358 (7), 345 (1 l),268 ( l l ) , 255 (51), 187 (20), 156 (21), 145 (25), 121 (33),119 (65), 94 (loo), and 73 (66); and (ii) the diol (27) Me,Siether, m/e 448 (M+, ,N) 1.38 (s, 20-H,), 1.42 ( s , 18-H,),3.87 and 4.24 ( J A ~ 10 Hz, 19-H,), and 4.26-4.47 (2- and3-H); v,.3 660-3 lOObr and 1 740 cm-l; wz/e (for tris-Me,Si ether) 538 (Mf, l ) , 448 (8), 358 (36), 345 (67),306 (24), 217 (17), 191 (38), 169 (26), 168 (30), 147 (34),143 (58), 103 (51), and 73 (100).Methyl ent-2P, 3P-Epoxy- l6-oxo- 17-norgibberellane-7,19,20-trioate (41) .--The bromohydrin (35) (250 mg), preparedfrom gibberellin A,, by the method of Beeley and Mac-Millan,, was dissolved in methanol (16 ml), and M-sodiumhydroxide ( I .4 Inl) was added dropwise. The mixture wasstirred for 20 11 a t 20 "C, then concentrated under vacuumand, after addition of water, extracted with methylenechloride to give crystals (180 nig).The crude productseparated as two bands upon p.1.c. on silica gel in ethylacetate-light petroleum (3 : 2). The band at RF 0.4 gavethe epoxide (41) (100 mg), which crystallised from ethylacetate-light petroleum as needles, m.p. 188-190" (Found:C, 62.5; H, 6.3; M', 420.178. C,,H,,O, requires C,J 12 Hz, 5-H), 3.04 (d, J 4 Hz, 3-H), 3.06 (dd, J 14 and3 Hz, 1-H), 3.28 (t, J 4 and 3 Hz, 2-H), 3.64 (s, CO,Me),3.77 (s, 2 CO,Me), and 3.94 (d, J 12 Hz, 6-H); v,,,. 1742,1728, 855, 846, and 836 cm-l; nz/e 420 (9), 388 (76),312 (43), 285 (51), 241 (36), 225 (loo), 197 (36), and 155 (39).Elution of the band a t RF 0.75 gave the bromolactone(42) or (43) (38 mg), which crystallised from ethyl acetateas prisms, m.p.241-242" (Found: M+, 468.079. Calc. forC,lH,,79Br0,: 144, 468.079); 6 1.37 (s, 18-H,), 2.75 (d,. 11 Hz, 5-H), 2.84 (cl. 12 Hz, I-H), 3.72 and 3.74 (hothC, 70.8; H, 9.4); 6 (CDCl,) 1.14 (s, 20-H,), 1.26 (s,H, 9.470; AZ, 322.214); 6 (CDCI,) 1.09 (s, 20-H,), 1.28 (s,62.8; H, 6.7:;; M , 420.177); 6 1.44 (s, 18-H,), 1.99 (d,s, 2 CO,Me), 3.81 (d, J 11 Hz, 6-H), 4.78 (td, J 4 and 1 Hz,2-H), and 5.18 (d, J 4 Hz, 3-H); v,,,,. 1 790, 1 742, and1733 cm-l; m/e 470 (M+, 2.9), 468 (M+, lo), 438 (loo),436 (loo), 410 (37), 408 (37), 225 (26), 197 (24), 155 (18),and 129 (16).Acidic Hydrolysis of the Epoxide (41) .-The ent-2P,3P-epoxide (41) (110 mg) in tetrahydrofuran (10 ml) wasrefluxed with M-sulphuric acid (1.5 ml) for 2 h.Themixture was neutralised with aqueous sodium hydrogencarbonate ; the tetrahydrofuran was evaporated off undernitrogen and the residue was extracted with ethyl acetateto give the crude product (135 mg). P.1.c. in ethyl acetate-light petroleum (4 : 1) and elution of the band at RF 0.15gave methyl ent-2a, 3P-dihydroxy- 16-oxo- 17-norgibberellane-7,19,20-trioate (44) (68 mg), which crystallised from ethylacetate-light petroleum as prisms, m.p. 195-205" (Found :C, 59.9; H, 6.8. C22H,,O9 requires C, 60.3; H, 6.9);6 1.32 (s, 18-H3), 2.22 (d, J 12 Hz, 5-H), 2.74 (dd, J 13 and5 Hz, 1-H), 3.04 (d, J 10 Hz, 3-H), 3.64, 3.70, and 3.73 (alls, 3 CO,Me), 3.96 (d, J 12 Hz, 6-H), and 4.15 (m, Wt 26 Hz,2-H); vInax.3 585, 3 545, 1 740, and 1 722 cm-l; m/e (forbis-Me,Si ether) 582 (M+, 2), 567 (6), 433 (loo), 351 (15),217 (18), 204 ( l l ) , 188 (19), 173 (33), and 147 (32).Starting material (41) (37 mg) was recovered from theband a t RF 0.5.ent-3P-Hydroxy- 17-norkauran- 16-one.-The ent-3P-alcohol (19) (200 mg) was dissolved in tetrahydrofuran (13ml) and water (13 ml) a t 0 OC, and a few crystals of osmiumtetraoxide were added. Sodium periodate (390 mg) wasthen added to the mixture, which was subsequently allowedto warm to room temperature. After 12 h, work-up withethyl acetate and subsequent p.1.c. in ethyl acetate-lightpetroleum (35 : 65) with removal of the band a t RF 0.3 gavethe nor-ketone (142 mg), which crystallised from acetone-light petroleum as microprisms, m.p.188-190" (Found :Mf, 290.226. ClgH,@, requires M , 290.225); 6 0.81 (s,20-H,), 1.01 (s, 19-H3), 1.10 (s, 18-H3), and 3.23 (m, W )18 Hz, 3-H) ; v,,,~ 3 620 and 1 740 cm-l.(33) .-ent-SP-Hydroxy- 17-norkauran- 16-one ( 138 mg) was dissolved in pyridine (8 ml)containing phosphoryl chloride (400 yl), The mixture wasleft for 12 h a t 20 "C and then heated a t 100 "C for 1 h.Aqueous work-up and extraction into ethyl acetate gave apink solid (150 mg), which was redissolved in ethyl acetateand the colour removed by elution from a column of silicagel to yield the olefin (33) (100 mg). Recrystallisation fromaqueous methanol gave needles, m.p. 108-1 10" (Found :M+, 272.215. C,,H,,O requires M , 272.214); 6 0.92 ( s ,2O-H,), 0.98 (s, 19-H,), 1.13 (s, 18-H,), and 5.42 (m, 2- and3-H); v,,,.1 740 cm-l.ent-2P-Acetoxy-3a-bi,orno- 17-norkauran- 16-one (36) .-Theolefin (33) (95 mg) was dissolved in acetic acid (6 ml) andN-bromoacetamide (60 mg) and lithium acetate dihydrate(570 nig) were added. The mixture was stirred a t roomtemperature for 3 h, then added to water and extractedwith ethyl acetate. P.1.c. in ethyl acetate-light petroleum( 3 : 7) and recovery from the band a t RF 0.5 gave thebromo-acetate (36) (86 nig). Recrystallisation from ethylacetate-light petroleum afforded needles, m.p. 191-193"(Found: M+, 410.145. C,lH,179Br0, requires M, 410.145) ;MeCO,), 4.34 (d, J 7 Hz, 3-H), and 5.29 (9, J 6 Hz, 2-H);vmar. 1 740 cm-l; nz/e 412 (M+ + 2, 展开▼
