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【结 构 式】 
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【分子编号】15774 【品名】4-[(5R,5aR,8aR,9S)-9-hydroxy-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl benzyl carbonate 【CA登记号】 |
【 分 子 式 】C29H26O10 【 分 子 量 】534.51944 【元素组成】C 65.16% H 4.9% O 29.93% |
合成路线1
该中间体在本合成路线中的序号：(II)By reaction of 4,6-O-ethylidene-2,3-di-O-acetyl-beta-D-glucopyranose (I) and 4'-benzyloxycarbonyl-4'-demethyl-epipodophyllotoxin (II) in the presence of boron trifluoride etherate to give the compound (III), which is treated with Zn(OAc)2 and NaOAc followed by reduction with Pd-C.
| 【1】 Kuhn, M.; et al.; Verhafren zur Herstellung von Glucosiden. AT 303270B; AT 319971B; CH 514578; NL 6901619 . |
| 【2】 Cabanillas, F.; Etoposide. Drugs Fut 1979, 4, 4, 257. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 33218 | (2R,4aR,6R,7R,8S,8aR)-7-(acetoxy)-6-hydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-8-yl acetate | C12H18O8 | 详情 | 详情 | |
| (II) | 15774 | 4-[(5R,5aR,8aR,9S)-9-hydroxy-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl benzyl carbonate | C29H26O10 | 详情 | 详情 | |
| (III) | 33219 | (2R,4aR,6R,7R,8S,8aR)-6-[[(5S,5aR,8aR,9R)-9-(4-[[(benzyloxy)carbonyl]oxy]-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]oxy]-7-(acetoxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-8-yl acetate | C41H42O17 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation of 4'-O-(benzyloxycarbonyl)-4'-demethylepipodophyllotoxin (I) with allyltrimethylsilane (II) by means of boron trifluoride ethearate in dichloromethane gives 4beta-allyl-4'-O-(benzyloxycarbonyl)-4'-demethyl-4-desoxypodophyllotoxin (III), which is oxidized with OsO4 and N-methylmorpholine (NMO) in acetone to the substituted acetaldehyde (IV). The reductocondensation of (IV) with N,N,N'-trimethylethylenediamine (V) by means of sodium cyanoborohydride and acetic acid in CHCl3 affords the protected final product (VI), which is finally hydrogenated with H2 over Pd/C in methanol.
| 【1】 Leeson, P.A.; Castaner, J.; TOP-53. Drugs Fut 1996, 21, 11, 1136. |
| 【2】 Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.; Takeda, S.; Kobunai, T.; Yamaguchi, H.; Wierzba, K. (Taiho Pharmaceutical Co., Ltd.); 4-Desoxy-4-epipodophyllotoxin deriv. or pharmaceutically aceptable salt thereof. EP 0522173; JP 1993503298; WO 9212982 . |
| 【3】 Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.; Wierzba, K.; Shibata, J.; Sugimoto, Y.; Yamada, Y.; Antitumor agents. 3. Synthesis and biological activity of 4beta-alkyl derivatives containing hydroxy, amino, and amido groups of 4'-O-demethyl-4-desoxypodophyllotoxin as antitumor agents. J Med Chem 1993, 36, 12, 1689-99. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 15774 | 4-[(5R,5aR,8aR,9S)-9-hydroxy-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl benzyl carbonate | C29H26O10 | 详情 | 详情 | |
| (II) | 15775 | Allyltrimethylsilane; allyl(trimethyl)silane | 762-72-1 | C6H14Si | 详情 | 详情 |
| (III) | 15776 | 4-[(5R,5aR,8aR,9S)-9-allyl-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl benzyl carbonate | C32H30O9 | 详情 | 详情 | |
| (IV) | 15777 | 4-[(5R,5aR,8aR,9S)-6-oxo-9-(2-oxoethyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl benzyl carbonate | C31H28O10 | 详情 | 详情 | |
| (V) | 15778 | N-[2-(dimethylamino)ethyl]-N-methylamine; N,N,N'-trimethyl-1,2-ethanediamine; N(1),N(1),N(2)-trimethyl-1,2-ethanediamine | 142-25-6 | C5H14N2 | 详情 | 详情 |
| (VI) | 15779 | 4-((5R,5aR,8aR,9S)-9-[2-[[2-(dimethylamino)ethyl](methyl)amino]ethyl]-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenyl benzyl carbonate | C36H42N2O9 | 详情 | 详情 |