Terpenoids. Part II. Some ringDderivatives of 13β-kaurane

摘要

1972 981Terpenoids. Part 11.l Some Ring D Derivatives of 13P-KauraneBy J. MacMillan and E. R. H. Walker, School of Chemistry, The University, Bristol BS8 1TSMetal hydride reduction of 13P-kaur-I 6-en-l s-one afforded the 1 ,.l-reduction product, (1 6R)-13P-kauran-l5p-olbut none of the expected 1,2-reduction product, 13P-kaur-l6-en-15~-01; in concentrated solution, a dimer (1 9)was a minor product. Treatment of 13~-kaur-l6-en-15a-ol with aqueous acid in methanol yielded a dimeric ether(20) in addition-to 17-hydroxy- and 17-methoxy-13p-kaur-15-ene. The four isomers of 13P-kauran-15-01 wereprepared ; their m.p.s and optical rotations differed from those reported previously.A previously noted division of Crypromeria japonica into producers of ent-kaurene or 1 3P-kaurene has beenconfirmed for fifteen additional varieties.IN Part I 1 a twist envelope conformation for ring D in theent-kaur-16-en-15-01s (1) and (2) was suggested on thebasis of the J values for the allylic coupling between the15- and 17-protons* A16-carbonium ion, obtained by protonation of these 1967, 361.alcohols, was also proposed to explain the difference inthe rate of 15,16-hydride shift in the acid-catalysed re-arrangement of the two alcohols.The isomer (1) andconformation in the Part I, M. F. Barnes and J. MacMillan, J . Chew. SOC. (C)982 J.C.S. Perkin Iits 16-deuterio-analogue (3) readily yielded the (16R)-ketones (4) and (5), respectively; under the same condi-tions, the isomer (2) was stable. The present worksought to extend this study to the 13p-kaurane (phyll-ocladane) series.(1) R' = OH, R2 = H(2) R' = H, R2 = OH(3) R' = OH, R2 = 2H(4) R = H(6) R = 2HA source of 13p-kaurene (6) was required.Appletonet aL2 have examined ten varieties of Cry$tomeria ja$onicaand found that two contained 13p-kaurene. The othereight varieties contained ent-kaurene but none containedboth diterpene hydrocarbons. In an independentstudy we examined the leaves of fifteen varieties ofC. japonica and obtained similar results. G.1.c. analysesof light petroleum extracts showed that three varietiescontained 13p-kaurene but no ent-kaurene. The re-maining twelve varieties contained ent-kaurene but no13p-kaurene. The identity of the diterpene hydro-carbons was confirmed by isolation. C.juponica clearlyexists in two distinct chemotaxonomic groups which mustcontain independent cyclase systems for geranylgeranylpyrophosphate. Since ent-kaurene is an establishedbiosynthetic intermediate for the gibberellin group ofplant hormones, the acids from the ent-kaurene and 13p-kaurene varieties of C. japonica were examined forgibberellin-like biological activity. Both showed weakbut equal activity in the lettuce hypocotyl bio-assay.However in an extensive g.1.c.-mass spectral examinationof derivatives of the acids, no gibberellins could beidentified.3 Nor could the growth habit of the fifteenvarieties of C. japonica be correlated with the presenceor absence of ent-kaurene.Soxhlet extraction of C. japonica var. pendula on alarge scale gave a mixture of 13p-kaur-16-ene (6) and(6) R' = R2 = H(7) R' = H, R2 = OH(8) R1R2 = 0(9) R' = OH, Re = H(10) R = H(11) R = OH(12) R = OMe13P-kaur-15-ene (10) in yields of 0.5 and 0*2y0, respec-tively.The isomer (10) was absent in light petroleumextracts made at room temperature. Isomerisation ofR. A. .4ppleton, R. McCrindle, and K. H. Overton, Phylo-chemistry, 1968, 7 , 136.P. N. Strong, B.Sc. Thesis, University of Bristol, 1969.4 R. McCrindle, personal communication.5 S. Nagahama, Bull. Chem. SOC. Japan, 1963, 36, 763.the 16-ene (6) to the 15-ene (10) by heating the crudecold extract of C. japonica has been previously noted4and may be caused by the presence of abietic acid, whichis known to induce the analogous isomerisation ofent-kaur- 16-ene to ent-kaur- 15-ene.13p-Kaur-16-ene (6) was isomerised by iodine in boil-ing benzene to an equilibrium mixture containing 98of 13P-kaur-15-ene (10).Similar equilibration of -kaur-15-ene and -16-ene yielded a mixture contaiifi@75 of the endocyclic double bond isomer. The higherproportion of the 16ene in the 13p-kaurenes shows thegreater preference for sfi2-hybridisation at C-15 due tothe relief of steric compression with the 10-methyl group.Sensitised photo-oxygenation of 13p-kaur-16-ene (6) gavethe known6 15-en-17-01 (11) in 40 yield. Similarly13P-kaur-15-ene (10) was converted in over 85 yieldinto the known 6 p 7 16-en-15a-01 (7). The stereochemistryof the 15a-01 (7) was deduced from the reasonablepreference for reaction on the less hindered a-face andwas confirmed by n.m.r.studies (to be described in alater paper). Barnes et aL8 have suggested that the(13) 9PH R1 R2 R3 R4(14) 9aH (16) OH H Me HOH Me HEH H H Me(18) H OH H Mefailure to photo-oxygenate methyl epiallogibberate (13),in contrast to the 9aH-epimer (14), might indicatedifferent conformations of ring D in the two epimers as aresult of the differing C-9 stereochemistries. Howeverthe yield (40) of 13p-kaur-15-en-17-01 (11) from thephoto-oxygenation of 13p-kaur-16-ene (6) is onlyslightly lower than that (55) of ent-kaur-15-en-17-01from ent-kaur-16-ene and indicates little if any effect ofthe stereochemistry at C-9 on the ease of photo-oxygen-ation of these diterpenes.Reduction of 13p-kaur-16-en-15-one (8), obtained byoxidation of the 16-en-15a-01 (7), with sodium boro-hydride or lithium aluminium hydride failed to yield13p-kaur-16-en-15p-01 (9).The fully saturated alcohol,the (16R)-15p-ol (15), was obtained even under very mildconditions. This result contrasts with the smoothreduction of ent-kaur-16-en-15-one to the corresponding16-en-15p-o1.l This difference between the two seriesis probably due to the steric compression in the transi-tion state for 1,2-hydride addition between the develop-ing 15p-hydroxy-group and the lop-methyl function,L. H. Briggs, B. F. Cain, R. C. Cambie, and B. R. Davis,J . Chem. SOC., 1962, 1840.L. H. Briggs, R. C. Cambie, and P. S . Rutledge, J . Chem.SOC., 1963, 5374.8 M.F. Barnes, R. C. Durley, and J. MacMillan, J. Chem. SOC.( C ) , 1970, 13411972 983allowing 1,4-addition to predominate. 1 ,.Q-Reductionof enones with sodium borohydride is rare.g Reductionof the enone (8) with lithium aluminium hydride inconcentrated solution gave small amounts of the dimer(19), whose structure was deduced from the mass (M+574), i.r. (vDo 1730 cm-l, five-membered ring ketone),and n.m.r. spectra. The last showed five methylsinglets and a one-proton multiplet (T 6.45) which wasassigned to the 16'-proton since the signal collapsed onirradiation at T 8-43, the expected chemical shift for thel7'-protons. This low chemical shift for the 16'-protonmay be caused by deshielding from both carbonylgroups.Fragmentation in the mass spectrum is also inaccord with structure (19). McLaff erty rearrangementof the parent ion see arrows in (19) gives the base peak atm/e 288. The formation of the dimer (19) can berationalised in terms of hydride attack at C-17, followedby a Michael-type addition of the resulting anion to theenone (8).UThe failure to prepare 13p-kaur-16-en-15p-01 (9) pre-cluded a comparison of the rates of acid-catalysed 15,16-hydride shift in the two 15-epimeric allylic alcohols.The available 15a-01 (7) was much less stable to acidthan its counterpart in the ent-kaurane series.l Howeverthere was no evidence for 15J6-hydride shift since neither(16R)- nor (16S)-13p-kauran-15-one (21) and (22) wasdetected. The products depended upon the reactionconditions.At 0" in methanol containing concentratedhydrochloric acid, the major product was a non-polardimer which was decomposed by chromatography ormolecular distillation to a mixture of starting material(7) and 13p-kaur-15-en-17-01 (11). From this evidenceand the spectroscopic properties of a sample containing20 of the alcohols (7) and (11) as the only impurities,the structure (20) was assigned to the dimer. The n.m.r.spectrum contained a vinylic proton signal at T 4.31,showing allylic coupling to methyleneoxy-protons a t T5.94 and the presence of a 15,16-double bond was indi-cated by the shielded 10-methyl singlet at z 9~29.l~ At60°, the major product of the reaction of the 15~-01 (7)and methanolic hydrochloric acid was 17-methoxy-13p-kaur-15-ene (12) whose structure was assigned onH.0. House, ' Modern Synthetic Methods,' Benjamin, Newl o Y. Kitahara and A. Yoshikoshi, Bull. Chem. SOC. Japan,York, 1965, p. 40.1964, 37, 890.the basis of spectroscopic data, listed in the Experi-mental section. All three products ( l l ) , (12), and (20)are clearly derived by reactions of the intermediateallylic cation, with water, methanol, and the 16-en-15~01(7), respectively.The four isomers of 13p-kauran-15-01 were prepared inthe following way for n.m.r. studies (to be reported in asubsequent paper). The (16R)- and (16S)-kauran-l6a-01s (l6) and (18), respectively were obtained as aseparable mixture by hydrogenation of the 16-en-15~01(7), the 16R-isomer predominating as expected forpreferential a-hydrogenation.The isomers were charac-terised by their separate oxidation to the known7J1J2(16R)- and (lGS)-13p-kauran-15-ones (21) and (22),respectively. Thus prepared, these ketones were shownto contain less than 1 of each other by g.1.c. The(16R)- and (16S)-13p-kauran-lS~-ols ( E ) and (17),respectively were prepared from 13 p-kaur-16-en-15a-01(7) by the following route. Oxidation gave the 16-en-one (8), which underwent hydrogenation from thea-f ace exclusively to provide the ( 16R) -1 one (2 1).Epimerisation of the (16R)-ketone (21) with aqueousalkali gave an equilibrium mixture of the (16R)- and(16s)-ketones (21) and (22), respectively containing60 of the 16S-epimer (22).This xture could not beseparated by crystallisation or aasorption chromato-graphy and was directly reduced with lithium aluminiumhydride to a mixture of (16R)- and (lGS)-13P-kauran-lSp-01s (15) and (17), respectively, which were readilyseparated by preparative t.1.c. and characterised by theirseparate oxidation to the (16R)- and (16s)-ketones (21)and (22).The four epimeric alcohols (15)-(18) have been de-scribed by Turner et uZ.l2 and three of them (16)-(18)by Briggs et UZ.' The m.p. and optical rotation valuesobtained in the present work differ from the mil quotedby the previous workers (see Table). Our al~kd-~ls wereshown to be greater than 99 pure by g.1.c. and theassigned stereochemistries were confirmed by n.m.r.studies (to be reported).Reported m.p.s and optical rotations (chloroformsolutions) for the isomers of 13P-kauran-15-01sPresent(16) M.p.("C) 104-105Isomer workalD (") -9a D + 11@-ID +21(16) M.p. 105--109(17) M.p. 103-104(18) M.p. Oila DTurner et aLf2104-106 + 13- 6.6Briggs et aZ.7114-6-1 16.3 Oil94-95 157.6-168-3- 36 - 1281-82 11 1-1 15.6EXPERIMENTALM.p.s were determined on a Kofler hot-stage apparatusSilica gel M.F.C. (Hopkin and Williams)l1 R. Henderson and R. Hodges, Tetrahedron, 1960, 11, 226.12 R. B. Turner, K. H. Ganshirt, P. E. Shaw, and J. D. Tauber,and are corrected.J . Amer. Chem. SOC., 1966, 88, 1776J.C.S. Perkin Iand Mallinkrodt SilicAR T.L.C.-7G were used for columnand thin-layer chromatography respectively. 1.r.spectrawere obtained on a Perkin-Elmer 257 spectrophotometer forNujol mulls except where stated otherwise. Optical rota-tions were recorded on a Perkin-Elmer 141 polarimeter formethanolic solutions unless otherwise stated. N.m.r.spectra were obtained with a Varian HA100 spectrometerfor deuteriochloroform solutions with tetramethylsilane asinternal standard. Mass spectrometry was carried out withan A.E.I. MS9 spectrometer and the data were processedby an on-line Linc 8 ~0mputer.l~ G.1.c. was carried out on aPye 104 dual column gas chromatograph fitted with flameionisation detectors. Silanised glass columns (5 f t x inint. diam.) were packed with 2 QF-1 or 2 SE-33 ondemineralised and silanised Gaschrom A.Retentionindices were determined by use of n-alkane standards.Light petroleum boiled at 60-80".Extraction and Identijication of Diterpene Hydrocarbons.-The foliage, together with light terminal shoots of varietiesof Gryptorneria japonica, was dried at 25' for 3 weeks andextracted with refluxing light petroleum. After evapora-tion in vacuo, the residue was taken up in light petroleumand subjected to column chromatography over grade 1neutral alumina. The diterpene hydrocarbons were identi-fied by comparison with authentic samples of ent-kaureneand 13P-kaurene, by g.l.c., m.p., and optical rotation. Thefollowing varieties gave ent-kaurene : Elegans ; Compacta ;Viminalis; Hong Kong No. 31 (101-88) ; Jirdai-Sugi;Hong Kong No. 23 (101-88) ; Selaginiodes 365-04 Rovelli;Yenko-Sugi 252-08 ; Kusari Sugi 252-08 Yokohama No.15; No.29 25-93 Japan China; Vitellina 666-04 Rovelli No.12; and 101-88 Hong Kong No. 27. The following varietiesgave 13p-kaurene: Hong Kong No. 13 (101-88); Pendula528-13 Veitch 4007 No. 16; and Lobbii No. 11.Isolation of 13P-Kaurene .-C. japonica pendula cuttings(2.35 kg) were dried for 3 weeks a t 26' in air. The leaves(1-04 kg) were then removed, and Soxhlet-extracted withlight petroleum (15 1) for 7 days. Evaporation gave a darkgreen oil, which was dried (P,O,) to constant weight (76.1 g)and chromatographed on grade 1 neutral alumina (700 g).Elution with light petroleum gave a mixture (7-3 g) of13B-kaur-16-ene (6) and 13P-kaur-15-ene (10) , which wasseparated by preparative t.1.c. on silica gel impregnated withsilver nitrate (10) to give 13P-kaur-16-ene (6) (5.1 g)as plates, m.p.97-98" (from methanol); aID2a +15.6";vmax. 3070, 1658, and 873 cm-l; 7 9.21, 9-17, and 9.10 (each3H, s) and 5-03br (2H, s); and 13P-kaur-15-ene (10) (2.1 g )as needles, m.p. 113-113-5" (from ethanol-light petroleum) ;za +24' (c 0.2); vmX. 3055, 1638, and 828 cm-1; T 9.29,9.22, and 9.18 (each 3H, s), 8.37 (3H, d, J15,17 2 Hz), and4.75br (lH, s).13P-Kaur-15-erze (10).-13P-Kaur-l6-ene (6) (15 mg) andiodine (20 mg) in benzene (15 ml) were heated under refluxfor 9 h. The cooled mixture was washed with sodiumthiosulphate solution (2 x 10 ml) and (2 x 10 ml),dried, and evaporated to give 13P-kaur-l,.--_ ,e (10) (15 mg),containing only 2 13P-kaur-16-ene (6) (by g.l.c.), whichcrystallised from ethanol-light petroleum as needles, m.p.113-1 13.5', physical data identical with those of theproduct (1 0) already described.13P-Kaur-15-erz-17-oZ (11).-13P-Kaur-16-ene (6) (20mg) and haematoporphorin ( 5 mg) were dissolved in pyridine(5 ml) in a vertical glass tube (int.diam. 2-0 cm). Thesolution was irradiated for 96 h in a stream of dry oxygenby four fluorescent tubes (Phillips TLQW/33) mounted 2-3cm away. The solution was evaporated below 40" and theresultant crude hydroperoxide was reduced overnight inethanol (10 ml) containing acetic acid (2 drops) and sodiumiodide (500 mg) . The dark residue obtained by evaporationwas recovered in ether and washed with sodium thiosul-phate.Preparative t.1.c. on silica gel gave 13P-kaur-15-en-17-01 (11) (8 mg) as needles, m.p. 115-119" (from lightpetroleum); aIDaz +7" (c 0.46); vmax. 3590, 3300, and 839cm-l; T 9.28, 9.21, and 9.18 (each 3H, s ) , 5.90br (2H, s),and 4-45br (lH, s).13p-Kaur-16-en-15cc-oZ (7) .-13p-Kaur-l5-ene (10) (250mg) and haematoporphyrin (20 mg) in pyridine (20 ml)were oxygenated and irradiated as just described for 72 h.Work-up in the usual way gave an oil (290 mg), which waschromatographed on silica gel (30 g). Elution with lightpetroleum gave a mixture of 13P-kaur-16-ene and 13p-kaur-15-ene (80 mg) ; elution with 10 acetone-benzenegave 13P-kaur-16-en-15a-01 (7) (150 mg) as needles, m.p.112-113" (from methanol); +40" (c 0.24); vmL 3600,3470, 3080, 1660, 900, and 839 cm-l; t 9.21, 9.16, and 9.09(each 3H, s), 5.65br (lH, s), 5.06 (lH, s ) , and 4-90 (ZH, s ) .13@-Kaur-16-en-15-one (8) .-13P-Kaur-16-en-l5~-ol (7)(125 mg) in pyridine ( 5 ml) was added to a stirred suspen-sion of chromium trioxide (200 mg) in pyridine (5 ml) at 0".After 3.5 h at room temperature, the mixture u-as poured intoether (20 ml), washed with brine and water, dried, andevaporated to give 13P-kaur- 16-en- 1 one (1 2 1 mg) , whichcrystallised from acetone as needles, m.p.112-1 14" ;+71.3"; 0.r.d. 0, +I2,, +445o, +I2,,, -6260;Atzr5 - 1-97, AcZ18 +3.62, +3.16; A,, 235 nm (E6740); v,, 1725, 1645, and 928 cm-l; 7 9.25, 9.19, and9.17 (each 3H, s), and 4-98 and 4.20 (each lH, s).Reduction of 13P-Kaur-16-en-15-one ( 8 ) .-(a) Lithiumaluminium hydride.13P-Kaur- 16-en- 15-one (8) (25 mg) wasadded to a suspension of lithium aluminium hydride insodium-dried ether (25 ml). The mixture was boiled for9 h. Water (10 ml) was added and the solution stirred for afurther 5 min. The solution was extracted with brine andwater, dried, and evaporated to give an oil (24.2 mg).Preparative t.1.c. on three silica plates (0-3 mm x 20 x 20cm) benzene-petroleum (3 : 2) as eluant gave (16R)-13P-kauran-15P-01 (15) (18 mg) as needles, m.p. 104-105" (fromlight petroleum), identical with the product formed bylithium aluminium hydride reduction of (16R)-kauran- 15-one; and the dimer (19) (5 mg), m.p. 286-288"; vmx.1730, 1100, and 950 cm-1; T 9.22 and 9-18 (each 6H, s),9.08 and 9-05 (each 3H, s), and 6-45 (lH, m).Lithiumaluminium hydride reduction of 13P-kaur- 16-en- 15-one (8)in dilute ethereal solution (0.1 mg per ml) produced (16R)-13P-kauran-15P-01 (15) in quantitative yield.Sodium borohydride reductionof 13P-kaur-16-en-15-one gave (16R)-13p-lrauran-15P-ol asthe only isolable product.Acid Treatment of 13P-Kaur-16-en-15a-01 (7).-(a) A t 0'.13p-Kaur-16-en- 150(-01(7) (25 mg) was dissolved in methanol( 5 ml) and ether (2.5 ml) at 0", and hydrochloric acid (1 ml)was added. Theorganic solvents were removed at room temperature and theresidue extracted with ether (3 x 2 ml); the extract waswashed, dried, and evaporated to give an oil (25 mg), shownby t.1.c. to be a ca.1 : 1 mixture of starting material and acompound of high RF value. Preparative t.1.c. was carried13 R. Binks, R. L. Cleaver, J. S. Littler, and J. MacMillan,Chem. in Brit., 1971, 7, 8.c.d. A~410 0, A E ~ , ~ -0.95, A ~ 3 5 4 -1.09, A0300 0, 0,(b) Sodium borohydride.The solution was stirred for 4.5 h at 0"1972 985out on two silica gel plates (0.3 mm x 20 x 20 cm), withbenzene-light petroleum (3 : 2). Elution of the band ofhigh RF value with benzene gave a mixture of three com-pounds, the original compound of high RF value and twopolar materials identified as 13p-kaur-16-en-15a-01 (7) and13P-kaur- 15-en-17-01 (1 1) by comparison with authenticsamples. The following spectroscopic data were obtainedfor an 80 pure sample of the compound of high 11F valuewhich was assigned structure (20) the 20 impurity was amixture of the alcohols (7) and ( l l ) : v,,, 3590, 3350,1035, 900, and 840 cm-l; T 9.29, 9.22, and 9.18 (each 6H, s),5.94br (4H, s ) , and 4-31br (2H, s ) .When the foregoing reaction was carried outa t 60°, although dimer (20) was formed, the major product,partially purified by t.1.c.on silica gel plates, was identifiedas 17-methoxy-13p-kaur-15-ene (12) , vmX. 1100 and 840cm-1; T 9.28, 9.22, 9.18, and 6-74br (each 3H, s), and 4-44brHydrogenation of 13P-Kaur- 16-en-15a-02 (7) .-13p-Kaur-16-en-15~-01 (20 mg) in ethanol (10 ml) was hydrogenatedover 2 palladium-barium carbonate (20 mg) a t roomtemperature and pressure for 3 h. After removal of thecatalyst by filtration through sodium sulphate, evaporationgave a white crystalline solid (20 mg).Preparative t.1.c.on three silica plates (0.4 mm x 20 X 20 cm) with 5acetone-light petroleum yielded (16R)-13P-kauran-15a-ol(16) (16.5 mg), RF 0-4, m.p. 105-109" (from light petroleum)(Found: M+, 290.260. Calc. for C20H340: M , 290.261); ~ l ~ ~ ~ +11"; vmx 3580 and 3480 cm-l; T 9.22, 9-18, and9.10 (each 3H, s ) , 8-96 (3H, d, J16.17 6.5 Hz), 6.27 (lH, d,J15,16 4 Hz); and (16S)-13P-kauran-15a-ol (18) (3 mg),RF 0-5, a clear oil (Found: M+, 290.260. Calc. forC,,H,,O:M , 290.261) ; vmx. (film) 3600 and 3450 cm-l, T 9.22, 9.18,and 9-10 (each 3H, s), 9-10 (3H, d, J16.17 7-5 Hz), and 5-84(2 1) .-13P-Kaur-l6-en-15-one(8) (27 mg) in ethanol (10 ml) was hydrogenated over 5palladium-charcoal (30 mg) for 5.5 h.After removal of thecatalyst by filtration, evaporation yielded (16R)-13p-kauran-15-one (21) (25 mg) as plates, m.p. 103-104"(from methanol) ; - 64"; 0.r.d. $I,,, - 730,(b) A t 60".(1H, s ) .(lH* d* J l 5 . 1 6 Hz).(1 6R)- 13P-Kaurun- 15-one-7110, j62,g +6390, +2210, +Izo6 +4180; cad.A~350 0, As311 -2.82, A ~ 2 5 0 0, A~230 0, A E ~ O ~ -0.67; Am=. 300nm (c 81); vmx. 1730 cm-l; T 9-21 (3H, s), 9.18 (6H, s), and8.97 (3H, d, J16,I7 7.0 Hz).( 1622) - 13P-Kauran-l5~-ol(15) .-( 16R)-13P-Kauran-l5-one(10 mg) , in sodium-dried ether (2 ml), was added to a stirredsuspension of lithium aluminium hydride (10 mg) in sodium-dried ether (2 ml) . After 3 h a t room temperature, work-upin the usual way gave (1611)-13P-kauran-15~-01 (9 mg)as needles, m.p.104105" (from light petroleum) (Found:M+, 290.260. Calc. for C20H340: M , 290-261); aD22- 9"; v,,,. 3610 and 3480 cm-l; T 9.21 and 9.18 (each 3H, s) ,9.06 (3H, d, J z O , ? < 1 Hz), 9.12 (3H, d, J16,17 7.2 Hz), andEpipnerisation of (16R)-13P-Kauran-15-one (21) .-(16R)-13P-Kauran-15-one (21) (50 mg) was refluxed in 1 sodiumhydroxide in methanol (10 ml). The reaction was moni-tored by g.1.c. After 3 h under reflux the mixture was(lHJ dd, J15.16 l1, J15,OH Hz).cooled and evaporated and the residue was partitionedbetween water and ether. Work-up in the usual wayyielded a mixture (4: 6) of epimeric (16R)- and (16S)-13p-kauran- 15-ones (20 mg) .Further treatment with base did not alter the ratio of1622- to 16s-epimers.(16S)-13~-Kauran-15~-02 (17).-A mixture of (16S)-13P-kauran-15-one (22) (62) and (1622)-13P-kauran-l5-one (21)(38) (50 mg) in sodium-dried ether (10 mg) was added toa stirred suspension of lithium aluminium hydride (50 mg)in sodium-dried ether (30 ml) a t room temperature. After3 h, water was added and the mixture was stirred for afurther 5 min. Work-up in the usual way gave an oil (51mg).Preparative t.1.c. on three silica plates (0.4 mm x20 x 20 cm) developed with benzene-light petroleum (3 : 2)yielded (1622)-13P-kauran-15P-ol (15) (19 mg), needles, m.p.104-105" (from methanol) and the (16S)-13P-01 (17) (28mg), needles, m.p. 103-104" (from methanol) (Found :M+, 290.258.Calc. for C2,H,,0: M , 290-261); aID22+21"; vmX. 3580 and 3440 cm-l; T 9.23, 9.19, and 9.03(each 3H, s ) , 8.98 (3H, d, J16.17 7.0 Hz), and 6.76 (lH, d,Oxidation of (1 6R)-13P-Kauran- l5P-01 (15) .-( 16R)-13p-Kauran-l5P-o1(15) (15 mg) in dry pyridine (5 ml) was addedto a stirred suspension of chromium trioxide (20 mg) in drypyridine (5 ml) a t 0". The mixture was allowed to warm toroom temperature and stirred for 3 h. Recovery of theproduct in ether in the usual way gave (1612)-13P-kauran-15-one (21) (14 mg), crystallised from acetone as plates, m.p.203-104". G.1.c. showed the complete absence of (16s)-13P-kauran-15-one (22).( 16S)-13~-Kauran-l5-one (22) .-( 16s) - 13P-Kauran- 15p-01(17) (25 mg) in dry pyridine (5 ml) was oxidised withchromium trioxide (35 mg) in dry pyridine (5 ml) a t 0" asin the previous experiment. Recovery of the product inether gave (16!5)-13p-kauran-15-one (22) (25 mg) as plates,m.p. 128.5-129.5" (from acetone) ; aD22 - 64" (c 0.42) ;J15.16 5'5 Hz)'o.r*d* #'I400 - $I330 -6850J $I289 $- 2860, $1228,-4850, 4Iaos 0; c.d. 0, A~311 -2.05, 0,-2.43; A,, 303 nm (E 66) ; v, 1725 cm-l; T 9.22, 9.17,and 9.15 (each 3H, s), and 8.94 (3H, d, J16.17 7.5 Hz).Oxidation of (1 6R) -13P-Kauran- 15a-ol ( 16) .-( 1611) -1 3p-Kauran-l5a-01 (16) (15 mg) in dry pyridine (5 ml) wasoxidised by chromium trioxide (20 mg) in dry pyridine(5 ml) a t 0" as before. The usual work-up gave (1622)-13p-kauran-15-one (21) (14 mg), m.p. 103-104"1 identical withthat formed by hydrogenation of 13P-kaur- 16-en- 15-one (8).Oxidation of (1 6s) - 13P-Kauran- 15~-oZ ( 18) .-( 16S)-13p-Kauran-l5a-01 (18) (7 mg) was similarly oxidised to give(16S)-13p-kauran-l5-one (22) (5-5 mg) , identical with thatobtained by oxidation of (16S)-13P-kauran-15P-o1 (17).We thank the Worshipful Company of Salters for a Re-search Scholarship (to E. R. H. W.). We also thank theCurator, Royal Botanic Gardens, Kew, for his co-operationin supplying the terminal shoots of fifteen varieties ofC. japonica and Dr. P. M. Scopes, Westfield College, forthe 0.r.d. and c.d. data.1/2265 Received, 29th November, 1971