1976 857Lichens and Fungi. Part XI1.l Dehydration and lsomerization of StictaneTriterpenoidsBy R. Edward Corbett * and Aiistair L. Wilkins, Chemistry Department, University of Otago, Dunedin, NewZealandN.m.r. spectral data of a number of stictane derivatives have provided further support for the structure proposed forstictane, and the absence of an 8P-methyl group in this series of compounds has been verified.IN Part XI l we reported the isolation from lichens of theSticta genus and some chemical transformations of tentriterpenoids derived from a new parent triterpenoid towhich we gave the name stictane. We now report(2a) have an 8a-methyl group and a boat structure forring B rather than the usual 8p-methyl group and chairring B, hitherto found in pentacyclic triterpenoids.Attention has been drawn1 to the close similaritydehydration, isomerization, and spectroscopic studieswhich confirm that stictane (la) and the related flavkanePart w.J. Chin. R. E. Corbett, c. K. Heng, and A. L.Wilkins, J.c.S. Perhirt I , 1973, 1437858 J.C.S. Perkin Ibetween the mass spectra of stictane and flavicane andthose of the pentacyclic triterpenoids hopane, 18ct-oleanane, 14~-taraxerane, and gammacerane. In allthese spectra the base peak is at m/e 191 and is attributedto two fragments each of the same mass resulting frominitial cleavage of the 8,14-b0nd.~ The production ofthese two fragments requires that these pentacyclicstructures should contain four ring A/B methyl groups andfour ring D/E methyl groups. Furthermore, the presenceof oxygen functions attached to the terminal rings atC-3 in ring A and C-22 in ring E, in the ten stictanes so faris present in 5(4 ---t 3)abeo-stict-3-ene derivatives.Such an effect is not present in 5(4 + 3)abeo-triter-penes having the usual tvans,anti,trans-ABc ring structurewith rings B and c in the usual rigid chair conformation,as for example in hopane and lupane, etc.(Table 2). Thegreater flexibility of the boat ring B will account for thetransmission effect observed in the abeo-stictanes.In 5(4 _t 3)abeo-stict-3-ene derivatives the C-8methyl resonance is ca. 0.08 p.p.m. downfield from theC-8 methyl resonance in corresponding stictane deriv-atives. The C-8 methyl group must be deshielded by theR rsquo; R 2 R 3( t l a ; H H Hb; H OH OAcc ; H H OAcd; H H O He; OAc OAc OH( 3 ) a ; R = OAcb ; R = OHisolated,l implies on biogenetic grounds, that cyclizationis initiated in the usual manner by protonation ofsqualene 2,3-oxide and terminated without proton,methyl, or backbone rearrangements, by hydration of aring E cation with loss of a pr0ton.l These mass spectraland biogenetic observations imply that methyl groupsare to be expected at C-4(2), C-10, C-8, C-14, and C-18,and two in ring E, and the stictane structure fulfils thisrequirement.Deydration of 22a-acetoxystictan-3p-01 (lb) withphosphorous pentachloride gave the 5(4 __t 3)abeo-acetate (3a).1 A comparison of the methyl resonancesof this acetate with those of 22ct-acetoxystictane (lc)reveals that significant changes have occurred in theC-8, C-14, C-18, and one of the C-21 methyl signals(Table 1).Similar changes distinguish the n.m.r. spectraof the 5(4 __._t S)abeo-alcohol(3b) and stictan-22a-01 (Id),and indicate that a conformational transmission effectM. N. Galbraith, C . J. Miller, J. W. L. Rawson, E. Ritchie,J. S. Shannon, and W. C . Taylor, Austral. J . Chem., 1965,18, 226.Rrsquo; R 2 R 3( 2 ) a ; H H Hc; H OH He; H H 0 2 C . C C 13b; H OAc Hd ; OAC OAC HRrsquo; R 2 R 3 R b( 4 ) a ; OAc OAc C(:CHz)Me Hb; H OAc C(:CH2)Me H( 5 ) OAc OAc :C Me2Aexocyclic isopropylidene group. In the other 5(4 __t 3)-abeo-triterpenes listed in Table 2, all of which have8p-methyl groups, this methyl group is neither shieldednor deshielded. Molecular models indicate that a C-8methyl group, cc-oriented in a boat ring B structure,would be suitably positioned for that methyl group to bedeshielded as in 5(4 _t 3)abeo-stict-3-ene derivatives.Dehydration of 2~,3p-diacetoxystictan-22a-o1 (le)with phosphorus pentachloride gave a mixture (4 : 1) ofthe isomeric diacetates (4a) and (5).A comparison ofthe spectral data of (5) with those of (2d) and of flavica-2,21-diene (7a) with those of (7b) (Table 1) revealedthe absence of conformational transmission effects inthese ring-E-contracted stictanes, the flavic-21-enes, indirect contrast to the ring-amp;contracted stictanes. Thereis a similar absence of a conformational transmissioneffect in hop-21-ene (8).The C-18 methyl group in all8 D. H. R. Barton, A. J. Head, and P. J. May, J. Chem. SOC.,1957, 935.4 R. E. Corbett and R. A. J. Smith, J . Chem. SOC. (C), 1967,16221976 859these 21-enes is very strongly shielded and its signalappears at or near 6 0.57 (Table 1).Each of the diacetates (4a) and (5) was isomerised withformic acid in chloroform into the diacetate (6a)pound (5) also gave (6a) with trichloroacetic acid into be expected. The structure proposed for flavicane(2a) in which rings CDE are antipodally related to ringsCDE of 2laH-hopane about the BC ring junction impliesCom- this spectral identity. The splittings of 16-H2, 20-H,,and 22-H (Figure 1) by the adjacent protons at C-16,TABLE 1Chemical shifts (6) of methyl groupsCompound ,----, lop $a 14p 18s 21a 21p22a-Acetoxy-5(4 3)abeo-stict-3-ene (3a) 1.66, 1.72 0.75 1.07 0.96 0.85 0.89 0.9322a-Acetoxystictane (lc) 0.82 0.86; 0.89 1.14 0.92 0.82 0.85 0.925(4 ,- 3)abeo-Stict-3-en-22a-oI (3d) 1.56, 1.72 0.76 1.06 0.97 0.76 0.89 0.98Stictan-22a-01 (la) 0.81 0.86 0.90 1.14 0.91 0.73 0.86 0.984p 4a2a, 3@-Diacetoxyflavic-2 1-ene (5) 0.89 1.04 0.89 1.16 0.89 0.662a,3@-Diacetoxyflavicane (2d) 0.90 1.03 0.90 1.16 0.90 0.65Flavica-2,21-diene (7a) 0.92 0.89 0.89 1.12 0.89 0.68Flavic-2-ene (7b) 0.92 0.89 0.89 1.13 0.89 0.6548 4a lo@ Sp 14a 18aHop-21-ene * (8) 0.78 0.81 0.83 0.95 0.94 0.662laH-Hopane * 0.78 0.81 0.83 0.95 0.92 0.64* Ref.8. t J 6-7 Hz.22+----l 1.66, 1.720.79,* 0.89 *1.56, 1.720.79,* 0.90 *221.56 1.720.77 t 0.87TABLE 2Substituent effects (p.p.m.)4u Other# 74P Ring ~ / 5 ( 4 __t 3)abeo-3-ene ,.-L---, lop C-8 C-14Stictane series (+0.75, +0.86) -0.14 -0.08 +0.06 +0.03 f0.03 0.00Hopane series (+0.73, +0.88) -0.24 0.00 0.00 0.00 0.00 0.00Lupane series b (+0.74, +0.89) -0.23 +O.Ol 0.00 0.00 0.00 0.00Allobetulane series c (+0.76, +0.88) -0.22 0.00 0.00Dammarane series (+0.76, 1-0.89) -0.23 0.00 0.00c-22Ring ~/21-ene C-18 (--A-------,Mavicane series 0.00 0.00 0.00 0.00 0.00 -0.07 (+0.77, +0.83)2 1 aH-Hopane series 0.00 0.00 0.00 0.00 0.02 -0.08 (f0.79, +0.84)* Where more than one example was available the average effect is recorded.a S.Huneck and J, M. Lehn, BulZ. SOC. chim. France, 1963, 1702.* J. M. Lehn and A. Vystreil, Tetrahedron, 1963.19, 1733.J.hl. Lehn and G. Ourrison, Bull. Soc. ckim. France, 1962,1137. J. M. Lehn, Bull. SOC. cham. France, 1962, 1832.chloroform, but (4a) gave 2or,3~-diacetoxy-22-trichloro-acetoxyflavicane (2e) with this reagent. The acetateR ' R 2( 6 ) a ; OAc ct-H,OAcct-H,OAcR' C; H a - H , O Hn d; OH a-H,OHe; OAc ct-H,OHf ; O H a-H,OAc9; OAC 0R2hi H 0SCHEME Reagents: i, KOH-EtOH; ii, Ac,O-pyridine; iii,Jones oxidation; iv, Ca-liq. NH,; v, LiAlH,; vi, Ac,Gp yridine(6b) and the alcohol (Gc) were prepared as outlined in theScheme. The similarity of the three ring E methylresonance (Table 3) and of the multiplets arising from thefive protons allylic to the 17,21-double bond (Figure 1) inthe n.m.r. spectra of compounds (9a and b) and (6a-c) isC-19, C-29, and C-30 must be the same in all the com-pounds.Also since rings D and E of both the hopenesand the flavicenes are stereochemically similar thechemical shifts of the lines of all the patterns must bethe same. Any difference in the stereochemistry ofrings CDE of flavicane, a boat ring c or a cis-cD-ringjunction for example, would result in a change in theabsolute values of the chemical shifts because of achange in the anisotropy, and in the splitting patternsbecause of a change in the flexibility of ring D..2.632-522.70,FIGURE 1 Multiplet typical of allylic protons at C-16 (2 H),-20 (2 H), and -22 (1 H) in compounds (9a and b) and(6a-c)While a 17,21-double bond has no appreciable effecton the signals of the C-8 and C-10 methyl groups in thJ.C.S.Perltin Ihopane series it has a pronounced effect on the signalsfrom these methyl groups in the flavicane series. Aconformational transmission effect does not appear tooperate in the hopane compounds but is clearly seen inthe flavicane derivatives (Table 3). On the basis of theproposed flavicane structure the tendency to distortion ofring c caused by the introduction of a further element ofstrain into rings D and E, the 17 21-double bond, isreduced by some flexing of the relatively mobile boatring B, and thereby gives rise to the observed changes inthe chemical shifts of the C-10, C-8, and C-14 methylgroups, In the hop-l7(2l)-ene series, the rigidity of theBuckley et aL6 have shown that for the purposes ofcomparison it is convenient to normalize the results togive a value of 10.0 to the shift of the 4p methyl group inthe case of 3p-hydroxy-triterpenoids.Because of thelinear relationships established for concentration andtemperature the normalization procedure removes theneed for precisely defined experimental conditions.6The normalized chemical shifts of methyl groups inflavican-3p-01 (2c) and flavic-17(21)-en-3fi-o1 (6c) havebeen measured and compared with those determinedfor 18~-oleanan-3p-01 (10) and dammara-2OI24-diene-3p-01 (11) (Table 4). Clearly in each of compounds (Zc),TABLE 3Chemical shifts (6) of methyl groups and 17(21)-ene substituent effects (p.p.m.)21 aH-Hopane 0.78 0.81 0.84 0.95 0.92 0.64 0.77, 0.87Hop-l7(21)-ene (9a) 0.79 0.83 0.84 0.94 1.06 0.84 0.91, 0.987P-Acetoxy-21 aH-hopane 0.80 0.82 0.87 1.08 1.00 0.64 0.78, 0.897p-Acetoxyhop-l7(2l)-ene (9bj 0.78 0.83 0.86 1.07 1.13 0.83 0.90, 0.983P-Acetoxyflavicane (2b) 0.86 0.86 0.89 1.14 0.90 0.64 0.79, 0.903P-Acetoxyflavic-l7(21)-ene (6b) 0.85 0.86 0.94 1.09 0.96 0.81 0.91, 0.972a,3P-Diacetoxyflavicane (2d) 0.90 1.03 0.90 1.16 0.90 0.65 0.79, 0.892a-3P-Diacetoxyflavic-17 (21)-ene (6a) 0.90 1.05 0.95 1.10 0.97 0.82 0.92, 0.98Flavican-3P-01 (2c) 0.78 0.98 0.87 1.14 0.90 0.64 0.79, 0.89Flavic-17 (2 l)-en-3@-01 (6c) 0.78 0.97 0.91 1.07 0.96 0.80 0.91, 0.9822 *Compound 4P 4a 10P 8 14 18 7+17(21) -Ene substituent effect $0.01 $0.02 0.00 -0.01 +0.13 +0.2017 (21) -Ene substituent effect -0.02 3-0.01 +O.Ol -0.01 +0.13 +0.1917( 21)-Ene substituent effect -0.01 -0.01 +0.06 -0.06 +0.06 +0.1717( 21)-Ene substituent effect 0.00 +0.02 f0.05 -0.06 +0.07 40.1717(2 1) -Ene substitueiit effect 0.00 -0.01 1-0.04 -0.07 +0.06 +0.16* d, J 6-7 Hz.TABLE 4Normalized methyl group shifts (p.p.m.)OtherCompound 4P 4c~ lop 8 14 18 ,----.-,Flavican-313-01 (2c) 10.0 8.95 4.15 1.28 1.10 0.49 0.11 0.09Flavic-17 (2 1) -en-3@-01 (6c) 10.0 8.96 4.24 1.27 1.20 0.51 0.11 0.04OtherC-17 ,-*-,18a-Oleanan-3/3-01 (10) 10.0 9.06 3.97 1.74 0.95 0.66 0.18 0.15Dammara-20,24-dien-3P-ol (1 1) 10.0 9.18 3.94 1.72 0.94 0.47 0.19 0.19all-chair pentacyclic structure precludes such flexing andthe steric strain imposed by the 17,21-double bond islargely absorbed in rings D and E.In the case of flavic-21-ene compounds the presence of the two chair rings, cand D, between ring B and the exocyclic isopropylidenegroup accounts for the suppression of any transmissionof bond angle strain to ring B from ring E.The ability of lanthanoid derivatives such as tris-(dipivaloy1methanato)europium Eu(dpm),3 to produce,in the n.m.r. spectra of alcohols, a spectacular increase indispersion is well e~tablished,~ and attention has beendrawn to the use of this shift reagent for determining thenumber of methyl groups in a triterpenoid and thelocation of their attachment to the carbon framework.66 (a) C . C . Hinckley, J. Amer. Chem. Soc., 1969, 91, 6160;(b) J. K. M. Sanders and D. H. Williams, Chem. Comm., 1970,422;(c) P.V. Demarco, T. K. Elzay, R. B. Lewis, and E. Wenkert, J .Amer. Chern. SOC., 1970,92, 6734, 6737.(6c), (lo), and (ll), the europium atoms must occupy thesame mean position relative to the 3p-hydroxy- and 4a-,4p-, and lop-methyl groups common to each of thesecompounds. However the differences apparent in thenormalized chemical shifts of the C-8 and C-14 methylgroups of (2c) and (6c), when compared with those of the8a- and 14p-methyl groups of (10) and ( l l ) , verify thatflavicane, and hence stictane triterpenoids, differ fromtriterpenoids of the oleanane, hopane, and lupane seriesin their C-8 and C-14 configurations.Analysis of the methyl group shifts in terms of the(3cos20 - l)r3 proportionality now established forlanthanoid-induced shifts, is complicated by the lack ofprecision surrounding the exact location of the europium6 D.G. Buckley, G. H. Green, E. Ritchie, and W. C. Taylor,' A. E. Cockerill, G. L. 0. Davies, R. C. Harden, and D. M.Chem. and Ind., 1971, 298.Rackham, Chem. Rev., 1973, 667 and references cited therein1976atom relative to the hydroxy oxygen atom. If, inaccord with the deductions of other workers: theeuropium atom is considered to be ca. 3.2 A from theHR ' R 2 .( 9 1 a ; R = Hb; R = OACoxygen atom, and located along a line approximately inthe plane of the ring system, then for the essentiallyplanar 3p-alcohols (10) and (ll), the angle 8 between theoxygen, europium, and methyl group centres is relativelyinvariant, and in any case small.Thus the (3cos20 - 1)term can be equated to a constant, and a plot of thenormalized shift against rF3 should approximate to astraight line. By using methyl to europium atomdistances measured from models such a straight line plotis obtained (Figure 2) for compounds (10) and (ll), andalthough this procedure represents an oversimplificationof a complex problem, it is apparent that normalizedshift data are of value in locating methyl groups relativeto a reference 3p-hydroxy-group in triterpenoids such as(10) and ( l l ) , which have approximately planar struc-tures.Neglect of the (3cos20 - 1) term is, however, ofteninappropriate. For example Barry et aZ.* have notedthat in the analysis of the lH and I3C n.m.r. spectra ofcholesterol, the vinylic protons at C-6 and C-1 are both6.3 A from the europium atom, yet the C-1 has threetimes the induced shift of the C-6 proton.Withoutsome knowledge of the importance of the (3cos28 - 1)C . D. Barry, C . H. Dobson, D. A. Sweigart, L. E. Ford, andR. J. P. Williams, ' Nuclear Magnetic Shift Reagents,, AcademicPress, New York and London, 1973, p. 181.861term in the analysis of reference compounds possessinga boat ring B, such as protostan-3p-o1~,~ it is difficult toquantify the effect that this structural feature wouldhave on normalized shifts, especially those of the 8a-methyl groups in (2c) and (6c) for which 0 is estimated tobe at least 10" greater than 8 for any ring B atom in thecholesterol or 18a-oleanan-3p-01 skeletons.Althoughmodels indicate that an 8cx-methyl group in a flavicaneskeleton would be closer to a europium atom than an8p-methyl group is in 18a-oleanan-3p-01 (lo), theobservations of Barry et aL8 lead to the conclusion thatin the former case, the greater 0 value would result in the8cx-methyl group of (2c) or (6c) having an induced shiftappreciably smaller than that predicted from distanceconsiderations alone.In the flavicane skeleton, because of the boat ring B,the molecular framework is bent downwards at the ringBC junction, and in consequence the 14p-methyl group in(2c) would have a smaller 8 than that for the 14cx-methylgroup in (10). Models indicate the europium to C-14methyl group distances in these compounds to beapproximately the same.However the slightly greaternormalized shift for the 14p-methyl group in (2c), incomparison with that of the 14a-methyl group in (10)(Table a), can be rationalized in terms of the lesser valuefor 0 in the former case.Z10-3f -3FIGURE 2 Plot of normalized methyl group shifts againstf 3 for 18a-oleanan-3P-01 (10) and 3P-hydroxydammara-20,24-diene (11) r = distance (A) of methyl group from europiumatomModels also indicate the C-17 methyl group in (10) andthe C-18 methyl group in (2c) and (6c) to be almostequidistant from the 3p-hydroxy-group, and to have@ S. Okuda, Y . Sato, T. Hattori, and H. Igarashi, TetrahedronLetters, 1968, 4769862 J.C.S. Perkin Isimilar 6 values; hence the similarities in the normalizedshifts of these methyl groups are as would be expected.It is also noteworthy that the data (Table 4) for (2c) and(6c) are consistent with the ring E structure proposedpreviously 1 for stictane (la), in which a gem-dimethylgroup is located at C-21 and a methyl group at C-18,rather than an 18a-oleanane type of structure in whichthe gem-dimethyl group is at C-19 and a methyl groupat C-17.Ring contraction of a 3P-substituted stictan-22a-01 thus gives flavican-3p-01 derivatives in which thenormalized shift of the C-18 methyl group is greaterthan those of the two more remote secondary methylgroups of the isopropyl group, whereas in lup-Z0(29)-en-3p-01, which is a ring-E-contracted 18a-oleanane, theC-17 methyl group has a smaller normalized shift thanthat of the vinylic methyl group of the pendant iso-propenyl group.6The spectral data presented here are consistent withthe structures proposed for flavicane (2a) and stictane(la),l and support the conclusion that these structuresmust differ from the 18a-oleanane type of structure (10)at the BC ring junction, with the chemical shifts of theC-8 and C-14 methyl groups markedly different.Theboat ring B, with a P-H at C-9 and an a-Me at C-8 in thestictane and flavicane structures, will account for theobserved differences.EXPERIMENTALExperimental procedures are as described in Part VI.102a, 3P-DiacetoxyjZavicane (2d) .-2a, 3P-Diacetoxyflavic-22(29)-ene (4a) (100 mg) in AnalaR ethyl acetate (25 ml)was hydrogenated over Adams catalyst for 2 h (uptake 1niol.equiv.). Removal of the catalyst and evaporation gave2a,3~-diacetoxyfEavicane (2d) (95 mg), m.p. 203-205" (fromhexane); vw 1 740 and 1 245 cm-1 (OAc); 6 1.97 and 2.03(3 H each, s, OAc), 4.74 (1 H, d, J 5 Hz, CH-OAc), and 5.16(1 H, sextet, CH-OAc) (Found: C, 77.4; H, 10.7.C3*HS604 requires C, 77.2; H, 10.7).2a,3(3-Diacetoxy$avic-21-ene (5) and 2a,3P-Diacetoxyflavic-22(29)-ene (4a) .-A solution of 2a, 3P-diacetoxystictan-22~-01 (le) (300 mg) in benzene-hexane (1 : 9; 30 ml) wasstirred with an excess of freshly sublimed phosphorus penta-chloride (500 mg) . After 20 min a t room temperature, themixture was filtered and worked up in the usual way.Separation of the products (280 mg) by multiple ( x 2) p.1.c.on silver nitrate-impregnated silica gel with E-H (1 : 9)gave compounds ( 5 ) (55 mg) and (4a) (170 mg).2a,3p-Diaceto~y~avic-21-ene (5) (higher Rp) had m.p. 180-182"(sublimed sample) ; vmx. 1 735 and 1 250 cm-l (OAc) ; 6 1.56and 1.72 (3 H each, s, C=CCH,), 1.97 and 2.03 (3 H each, s,OAc), 4.74 (1 H, d, J 5 Hz, CH-OAc), and 5.16 (1 H, sextet,CH-OAc) (Found: C, 77.7; H, 10.5. Camp;5@4 requires C,77.5 ; H, 20.3). 2a,3P-Diacetoxyflavic-22(29)-ene (4a)(lower R p ) was identical (m.p. and mixed m.p., i.r. andn.m.r. spectra, and t.1.c.) with an authentic specimen.l2a,3P-DiacetoxyjZavic-l7(2l)-ene (6a).-(a) A solution of2cc, 3/3-diacetoxyflavic-2 1-ene (5) (80 mg) and trichloroaceticacid (30 mg) in chloroform (20 ml) was stirred for 24 h a troom temperature.The mixture was worked up in theusual way and the products separated by p.1.c. on silvernitrate-impregnated silica gel with E-H (1 : 7) to give as themajor product 2cc, 3p-diacetoxyflavic-17 (2 l)-ene (6a), m.p.176-178" (sublimed sample); v,, 1 735 and 1250 cm-l(OAc); 6 1.97 and 2.03 (3 H each, s, OAc), 2.18 and 2.77(5 H, m, CHCC), 4.74 (1 H, d, J 5 Hz, CH*OAc), and 5.16(1 H, sextet, CH-OAc); m/e 526 (M+), 511, 483 (loo),423, and 363 (Found: C , 77.6; H, 10.4. c,gHamp;g requiresC, 77.5; H, 10.3).(b) A solution of 2a,3P-diacetoxyflavic-21-ene ( 6 ) (150 mg)in chloroform (9.0 ml) and 98 formic acid (8.1 ml) was kepta t 20 "C for 18 h. The red colour that gradually developedwas discharged when the mixture was diluted with ether andwashed twice with water and then saturated aqueous sodiumhydrogen carbonate.Removal of the solvent underreduced pressure and filtration of the product in E-H (1 : 1)through alumina (8 g) gave 2a,3P-diacetoxyflavic- 17( 2 1)-ene(6a) (135 mg).(c) A solution of 2ax,3P-diacetoxyflavic-22(29)-ene (4aj(150 mg) in chloroform (9.0 ml) and 98 formic acid (8.1 ml)was kept a t 20 "C for 24 h. The red colour that graduallydeveloped was discharged when the mixture was dilutedwith ether and washed twice with water and then withsaturated aqueous sodium hydrogen carbonate. Removalof the solvent under reduced pressure and filtration of theproduct in E-H (1 : 1) through alumina (3 g) gave 2~,3p-diacetoxyflavic-l7(21)-ene (6a) (140 mg).2a, 3~-Diacetoxy-22-tric~Zmoacetoxy~avicane (2e) .-A solu-tion of 2a,3/3-diacetoxyflavic-22(29)-ene (4a) (50 mg) andtrichloroacetic acid (70 mg) in chloroform (15 ml) was stirredfor 3 h a t 20 "C.The mixture was worked up in the usualway and the products were separated by p.1.c. on silica gelwith E-H (1 : 7) to give unchanged (4a) (22 mg) and 2a,3p-diacetoxy-22-tr~chloroacetoxy~avicane (2e) (28 mg), vm= 1 735,1245 (OAc), 1 110, 1035, 860, 820, and 785 cm-l; 6 0.69(3 H), 0.89 (9 H), 1.03 (3 H), and 1.15 (3 H) (Me groups), 1.66(6 H, two s, Me,C*OR), 1.98 and 2.03 (3 H each, s, OAc),4.74 (1 H, d, J 5 Hz, CH-OAc), and 5.16 (1 H, sextet, CN9OAc); mle 888 (M+), 526 (loo), 466, 444, 438, 424, 406,363, and 328. Sublimation of this compound a t 150 "C and0.01 mmHg gave 2a,3P-diacetoxyflavic-21-ene ( 5 ) .Flavic-17(21)-ene-2cc,3~-diol (6d).-A solution of 2a,3P-diacetoxyflavic- 1 7 ( 2 1) -ene (6a) (500 mg) in ethanolic 2 potassium hydroxide (150 ml) was stirred for 5 h at roomtemperature.The mixture was worked-up in the usual wayand the product, in ether, filtered through alumina (15 g) togive flavic-17(21)-ene-2a,3~-dioE (6d) (455 mg), m.p. 220-222" (sublimed sample); vmX 3 330 and 3 240 cm-I (OH)(Found: C, 81.6; H, 11.5. Camp;amp;,O, requires C, 81.4;H, 11.4).Partial Acetylation of Flavic-l7(21)-ene-2a,3~-dioE (6d) .-A solution of (6d) (950 mg), in pyridine (80 ml) was stirredwith acetic anhydride (2.5 ml) at 20 "C until t.1.c. indicatedthat optimum monoacetylation had occurred (about 60min) .The mixture was worked up in the usual way and theproducts separated by multiple ( x 2) p.1.c. on silica gel withE-H (1 : l), to give, in order of decreasing RF values,compounds (6a) (80 mg), (6e) (390 mg), and (64 (390 mg),and unchanged diol { 6d) (70 rng) . 2a-A cetoxyflavic- 17 (21)-en-3p-ol (6e) had m.p. 216-218" (sublimed sample); 6 0.81(3 H), 0.85 (3 H), 0.96 (3 H), 1.04 (3 H), 1.08 (3 H), and 0.90and 1.00 (3 H each, d, J 7 Hz) (Me groups), 2.06 (3 H, s,OAc), 3.18 (1 H, d, J 5 Hz, CH-OH), and 5.00 (1 H, sextet,CH-OAc) (Found: C, 79.2; H, 10.9. C,,H,,O, requiresC, 79.3; H, 10.8). 3~-Acetoxyflavic-17(21)-en-2a-ol (6f)had m.p. 212-214' (sublimed sample); 6 0.81 (3 H),lo Part VI, R. E. Corbett and R. A. J. Smith, J . Chem.Soc. (C),1969, 4419760.87 (6 H), 0.96 (6 H), 1.10 (3 H), and 0.90 and 0.99 (3 Heach, d, J 7 Hz) (Me groups), 2.11 (3 H, s, OAc), 3.79 (1 H,sextet, CHeOAc), and 4.51 (1 H, d, J 6 Hz, CH*OAc) (Found:C, 79.4; H, 11.0). Hydrolysis of the diacetate (6a) andthe lower R p value hydroxy-acetate (6f) with ethanolicpotassium hydroxide gave the diol (6d). Three repetitionsof the partial acetylation cycle gave a 72 overall yield ofthe higher Rp value hydroxy-acetate (6e).Bcr-Acetoxyflavic-l7(21)-en-3-one (6g).-A solution of 2a-acetoxyflavic-17(21)-en-3~-ol (6e) (300 mg) in acetone (80nil) was stirred with a slight excess of Jones reagent. After3 min at room temperature the mixture was poured intosaturated sodium hydrogen carbonate solution and workedup in the usual way.P.1.c. on silica gel with E-H (1 : 4)gave fla-acetoxyf~avic-l7(21)-en-3-one (6g) (285 mg), m.p.204-206O (sublimed sample) ; v,, 1 750, 1 255 (OAc), and1710 cm-l (GO); 6 0.81 (3 H), 0.99 (3 H), 1.08 (3 H), 1.10(3 H), 1.13 (3 H), 1.19 (3 H), and 0.89 and 0.99 (3 H each, d,J 7 Hz) (Me groups), 2.13 (3 H, s, OAc), and 5.60 (1 H, q,CH*Ohc) (Found: C, 79.7; H, 10.6. CsZHS,O, requiresC, 79.6; H, 10.4).FZavic-l7(21)-en-3-one (6h) .-A solution of 2a-acetoxy-flavic-17(21)-en-3-one (6g) (500 mg) in toluene (25 ml) wasadded dropwise over 10 min to a vigorously stirred solutionof calcium (1.5 g) in redistilled liquid ammonia (250 ml).After stirring for a further 20 min, bromobenzene wasadded until the blue colour of the solution was discharged.The ammonia was allowed to evaporate at room temperatureand the mixture worked up in the usual way.P.1.c. onsilica gel with E-H (1 : 19) gave fluvic-l7(21)-en-3-one (6h)(385 mg), n1.p. 194-195" (sublimed sample); vmaZ 1705cm-l ( G O ) ; 6 0.77 ( 3 H), 0.81 (3 H), 0.98 (3 H), 1.04 (3 H),1.05 (3 H), 1.13 (3 H), and 0.91 :tnclO.98 (3 H each, d, J 7 Hz)(Me groups) (Found: C, 84.9; H, 11.1. C3,,Hd80 requiresC, 84.8; H, 11.4).FZuuic-17(21)-en-3~-oE (6c).-A solution of flavic-l7(21)-en-3-one (6h) (200 mg) in ether (50 ml) was stirred with aslight excess of lithium aluminium hydride for 1 h a t 20 O C .The excess of reagent was destroyed with wet ether and themixture worked up in the usual way. P.1.c. on silica gelwith E-H (1 : 3) gave flavic-17(21)-en-3P-oZ (6c) (190 mg),m.p. 182-184' (sublimed sample); vm9= 3 450 cm-l (OH);6 3.22 (1 H, m, CH-OH) (Found: C, 84.6; H, 11.7. C,,H,,Orequires C, 84.4; H, ll.8y0).3~-Acetoxyflavi~-17(2l)-ene (6b).-A solution of flavic-17(21)-en-3P-o1 (6c) (180 mg) in pyridine (10 mi) was stirredwith acetic anhydride (5 ml) for 24 h at room temperature,and the mixture worked up in the usual way. P.1.c. onsilica gel with E-H (I : 9) gave 3~-acetox~~avic-l7(21)-ene(6b) (175 mg), m.p. 196-19'7" {sublimed sample); vrnL?1 730 and 1 240 cm-l (OAc); 6 2.03 (3 H, s, OAc) and 4.50(1 H, m, CH*OAc) ; m/e 468 (M+, loo), 453,425,408,303,365, 191, and 189 (Found: C, 82.2; H, 10.9. C3,H,,0,requires C, 82.0; H, 11.2).Analyses were performed by the microanalytical Iabora-tory of this department under the direction of ProfessorA. D. Campbell. For an appointment to an HonoraryResearch Fellowship (to R. E. C.) during 1974 we thank theCommittee of University College, London, and for a Yost-graduate Scholarship (to A. L. W.) we thank the UniversityGrants Committee. This research has been assisted bygrants from the Mellor Research Fund of the University ofOtago, and from the Research Committee of the UniversityGrants Committee.5/1939 Received, 6th October, 1975
展开▼
