J. CHEM. SOC. PERKIN TRANS. I 1994 3231 A Convenient Enantioselective Synthesis of (+)-8-epi-Goniofufurone Zhi-Cai Yang and Wei-shan Zhou * Shanghai lnstitute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin L u,Shanghai 200032, China A convenient synthesis of (+) -8-epi-goniofufurone from methyl cinnamate has been completed. A key step is the intramolecular double cyclisation reaction. Recently, one of the styryl lactones, (+)-8-epi-goniofufurone 1, was isolated from the stem bark of Goniothalamus giganteus (Annonaceae) and shown to have cytotoxic activity. The structure of this goniofufurone 1 has been established by both spectroscopy and X-ray crystallography,' and its absolute configuration has been determined to be that shown, based on the synthesis of its enantiomer, (-)-8-epi-goniofufurone, starting from sugar^.^'^ As part of our work on styryl lactones, we recently described the asymmetric total synthesis of (+)-goniopypyrone from methyl inna am ate.^ Herein, we present a convenient synthesis from the same starting material of (+)-8- epi-goniofufurone 1 employing an intramolecular double cyclisation as the key step.0 1 Our previous work has indicated that methyl cinnamate 2 could be converted into the highly syn-selective adduct 3 in five steps with an overall yield of 46.4 Oxidation of the fury1 methanol 3 with tert-butyl hydroperoxide (TBHP), in the presence of vanadyl acetylacetonate, smoothly afforded the hydropyranone 4 as a mixture of the a-and p-anomers. Subsequent oxidation of the anomeric mixture of 4 with chromium(v1) oxide in acetic acid followed by immediate reduction with sodium triacetoxyborohydride in a 1 :1 mixture of isopropyl alcohol and acetic acid furnished the ally1 alcohol 5 (56 yield from the furan 3),4*5 -37.0 (c 1.2, in EtOH). The configuration of the 5-OH in compound 5 was confirmed after deprotection with trifluoroacetic acid (THF-water) provided the known trio1 6 in 90 yield (Scheme 1).6 In order to transform the six-membered ring lactone 6 into the five-membered ring lactone 8, we first tried acidic hydrolysis of 6 with HCI in THF, but no reaction occurred.Basic hydrolysis of compound 6 with 0.5 rnol dm NaOH followed by acidification of the resulting carboxylate with 1 mol dm-3 HCI unfortunately afforded the recovered lactone 6 as the major component.Finally, hydrolysis of the lactone 6 with 0.5 mol dm NaOH followed by treatment with 1 mol dm-3 HCl and CH2N2gave neither the expected ester 7 nor the lactone 8, but instead the ( +)-8-epi-goniofufurone 1directly, m.p. 194-1 95 "C, a6deg; 103 (c 0.3, in EtOH) {lit.' m.p. 190-192"C, Cali0 108 (c 0.2, in EtOH)}. On a six-membered a,P-unsaturated lactone, the intramolecular Michael reaction (forming the second six- membered ring) have to be initiated by a catalytic amount of DBU in THF.4*5However, this double cyclisation (lactonisation and intramolecular Michael addition) that could be performed in one pot, may be due to the easy formation of the five- membered ring.In summary, we have stereoselectively synthesized (+)-8-epi-OH 3 '4 iii1 0 0 II 6 5 .I OH OH 7 8 1 Scheme 1 Reagents and conditions: i, 5 steps;4 ii, TBHP, VO(acac),, CH,Cl,, OOC; iii, CrO,, AcOH, room temp., 20 min; then Pr'OH, NaBH(OAc),, -10 "C; iv, CF,CO,H, THF, H,O, room temp.; v, 0.5 mol dm-, NaOH, room temp. 20 min; then 1 mol dm 'HCl, CH,N, goniofufurone 1 from methyl cinnamate 2 in nine steps with an overall yield of 14. Experimental All m.p.s were uncorrected. 'H NMR spectra were recorded on a Bruker AM300 instrument with TMS as the internal standard; chemical shift values as given in Sand J values are given in Hz. Mass spectra were obtained on HP5890A spectrometer. IR Spectra were taken for solid samples as KBr pellets and for liquid samples as thin films, using a Shimadzu-440 spectro- photometer.Optical rotations were measured on a Perkin- Elmer 241MC polarimeter and aID values are given in values of 10- 'deg cm2 g-'. (2S)-6-Hydroxy-2-( 1 R,2S)- 1,2-isopropylidenedioxy-2-phen-ylethylJ-2,6-dihydropyran-3-one4.-To a stirred solution of the furan 3(1.129 g, 4.1 mmol) and VO(a~ac)~ (10 mg, 0.037 mmol) in CH,Cl, (20 cm3) was added TBHP (tert-butyl hydro- peroxide) (0.924 cm3, 6.18 mmol; 6.69 mol dm-, in CH2Cl,) at 0 "C. The solution was stirred for 10 h at 0 "C, and then Me,S (0.5 cm3, 6.8 mmol) was added at 0deg;C. After stirring for a further 30 min at 0 "C, water (20 cm3) was added. The organic layer was separated, and the aq.layer was extracted with CH2C12 (2 x 20 cm'). The combined organic layers were dried (MgSO,) and concentrated to give crude oil, which was purified by flash chromatography ethyl acetate-hexane (1 :5)J to afford the pyranone 4 as an inseparable mixture (1 :3) of the a-and p-anomers (1.04 g, 87) (Found: C, 66.05; H, 6.6. CI6Hl8O5 requires C, 66.19; H, 6.24); v,,,/cm-' 3340, 2950, 2890, 1700, 1620,1590,1440,1380,1360,1200,1160,1040,890,760 and 690; G,(CDCl,) 1.51 (3 H, s, Me), 1.55 (3 H, s, Me), 2.30 (1 H, br, OH), 4.39 (1 H, dd, J8.8 and 1.7,1'-H), 4.49 (1 H, d, J 1.7,2-H), 5.15 (1 H, d, J8.8,2'-H), 5.92 (1 H, d, J3.0,6-H), 6.19 (1 H, d, J 10.3,4-H),6.94(1 H,dd, J3.0and 10.3,5-H)and7.32-7.45(5H, m, Ph); m/z (EI) 251 (M+ -Me), 272 (M+ -H,O), 233,215, 197,184, 176,148,131, 126,119,105,97,77 and 43 (100).(5S,6R)-5-Hydroxy-6-(1R,2S)-1,2-isopropylidenedioxy-2-phenylethyl-5,6-dihydropyran-2-one5.-To a stirred solution of compound 4 (413 mg, 1.42 mmol) in acetic acid (5 cm3) was added chromium(v1) oxide (170 mg, 1.7 mmol) in acetic acid (3 cm3). After 15 min stirring at room temp., isopropyl alcohol (10 cm3) was added and the reaction mixture was stirred at constant temp. for a further 5 min. The resulting mixture was then cooled to -10 "C, and freshly prepared sodium triacetoxyborohydride prepared from NaBH, (270 mg) and acetic acid (8 cm3) below 10 "C was added. The reaction mixture was stirred for 1 h at the same temp. and then poured into water (50 cm3) and diethyl ether (20 cm3).The organic layer was separated and the aq.layer was extracted with diethyl ether (2 x 20 cm3). The combined organic layers were washed with brine, dried (MgSOJ and concentrated under reduced pressure. The residue was purified by flash chromatography ethyl acetate-hexane (1 :4) to give compound 5 (267 mg, 65) as a colourless oil, a;' -37.0 (c 1.2, in EtOH) (Found: C, 66.1; H, 6.4. Cl6Hl8o5 requires C, 66.19; H, 6.24); v,,,/cm-' 3350, 2910, 2830, 1700, 1610,1440,1360,1350,1260,1120,1060,890,860,810,740and 690;G,(CDCl3)3.61(1H,br,0H),4.12(1H,dd,J8.7and1.4, 1'-H),4.28(1 H,dd, J2.8and 1.4,6-H),4.30(1 H,dd, J5.2and 2.8,5-H), 5.31 (1 H,d, J8.7,2'-H),6.14(1 H,d, J9.6,3-H),6.94 (1 H, dd, J9.6 and 5.2,4-H) and 7.35-7.48 (5 H, m, Ph); m/z (EI) 291 (M++ l), 275 (M+ -Me), 233, 215, 197, 184, 176, 166, 148,133,126,119,97 (loo), 97 and 77.(5S,6R)-5-Hydroxy-6-( 1R,2S)-1,2-dihydroxyethyl-2-phenyl-ethyl-5,6-dihydropyran-2-one6.-To a stirred solution of com- pound 5 (146 mg, 0.5 mmol) in THF-H20 (1 :1, 6 cm3) was added trifluoroacetic acid (0.5 cm3). After stirring at room temp. overnight, water (10 cm3)was added. The organic layer was separated and the aq. layer was extracted with ethyl acetate J. CHEM. SOC. PERKIN TRANS. I 1994 (3 x 20 cm3). The combined organic layers were washed with brine, dried (NaSO,) and concentrated under reduced pressure. The residue was purified by flash chromatography ethyl acetate-hexane (3:1) to give the title compound 6 (225 mg, 90) as a white solid, m.p. 133-134 "C; aJko53 (c 0.5, EtOH) (Found: C, 62.1; H, 5.3.C13H1405 requiresC, 62.39; H, 5.63); v,,,/cm-' 3350,1710,1620,1490,1440,1380,1260, 1150,1020, 910, 820, 760 and 700; amp;(2H6Jacetone) 4.18 (1 H, dd, J 3.6 and2.8, 1-H),4.33(1 H,dd, J2.7and2.8,6-H),4.51 (1 H,dd, J 5.8and2.7,5-H),4.57(lH,l-OH),4.83(1H,2'-OH),5.04(1H, d, J3.6, 2'-H), 5.41 (1 H, SOH), 6.04(1 H,d, J9.7, 3-H), 7.07 (1 H, dd, J9.7 and 5.8,4-H) and 7.20-7.49 (5 H, m, Ph); m/z (EI) 250(M+), 232(M+ -HZO), 215, 188,173,162,149, 144,126, 107 (loo), 97 and 91. (+)-8-epi-Goniofufurone 1.-To a stirred solution of the trio1 6 (50 mg, 0.2 mmol) in THF (5 cm3) was added 0.5 mol dm-, NaOH (0.5 cm3,0.25 mmol). After stirring for 20 min at room temp., 1 mol dm-, HCl(1 an3,1 mmol) and CH,N, (in diethyl ether) were added and the reaction mixture was stirred at room temp.for a further 10 min. The resulting mixture was treated with sat. aq. NaHCO, (3 cm3) and organic layer was separated. The aq. layer was extracted with diethyl ether (2 x 10 cm3). The combined organic layers were washed with brine, dried (MgSO,) and concentrated under reduced pressure. The residue was purified by flash chromatography ethyl acetate-hexane (2: 1)J to give the title compound 1 (30 mg,60) as colourless needles, m.p. 194-195 "C; aJi' 103 (c 0.3, EtOH) (Found: C, 62.0; H, 5.5. C13H1405 requires C, 62.39; H, 5.63); v,,,/cm-' 3430,1650,1320,1000,820 and 695; GH(CDCI,) 2.71-2.79 (3 H, m, 3-H and -OH), 3.5 (1 H, br, -OH), 4.24 (1 H, dd, J 3.5 and 4.0, 7-H), 4.43 (1 H, dd, J 3.5 and 0.5, 6-H), 4.90 (1 H, dd, J4.0 and 0.5, 5-H), 5.09 (1 H, d, J4.0, 8-H), 5.12 (1 H, m, J 6.0 and 4.0, 4-H) and 7.347.45 (5 H, m, Ph); m/z (EI) 232 (M+ -HZO), 213, 199, 173, 149, 143, 126 (57), 107 (loo), 105 (64),97,91,82,79,77 and 55. Acknowledgements This research was supported by the National Sciences Foundation of China. References 1 X.-P.Fang, J. E. Anderson, C.-J. Chang and J. L. Mclaughlin, J. Nut. Prod. 1991,54,1034. 2 T.K. M. Shing,H.-C.TsuiandZ.-H.Zhou,Tetrahedron,1992,48,8659. 3 T. Gracza and V. Jager, Synlett., 1992, 191. 4 W.4. Zhou and Z.-C. Yang, TetrahedronLetr., 1993,34,7075. 5 M. Tsubuki, K. Kanai and T. Honda, J. Chem.SOC.,Chem. Commun., 1992, 1640. 6 T. K. M. Shing, H.-C. Tsui and Z.-H. Zhou, Tetrahedron Lett., 1993, 34,691. Paper 4/01 843E Received 28th March 1994 Accepted 25th April 1994
展开▼
