|
【结 构 式】 
|
【分子编号】64997 【品名】phenylmethyl 6-({2-[(chlorocarbonyl)(methyl)amino]-4-nitrophenyl}oxy)-3,4,5-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-carboxylate 【CA登记号】 |
【 分 子 式 】C39H63ClN2O10Si3 【 分 子 量 】839.6459 【元素组成】C 55.79% H 7.56% Cl 4.22% N 3.34% O 19.05% Si 10.03% |
合成路线1
该中间体在本合成路线中的序号：(V)The protected glucuronic acid derivative (I) is hydrolyzed under alkaline conditions to furnish (II). The alcoholic hydroxyl groups of (II) are subsequently protected as the silyl ether (III) employing t-butyldimethylsilyl triflate in the presence of DMAP. The carboxyl group of (III) is further converted to the corresponding benzyl ester (IV) by DCC-mediated coupling with benzyl alcohol. Acylation of amine (IV) with phosgene leads to the carbamyl chloride (V). (1,2)
| 【1】 Schmidt, F.; Monneret, C.; Prodrug mono therapy: Synthesis and biological evaluation of an etoposide glucuronide-prodrug. Bioorg Med Chem 2003, 11, 10, 2277. |
| 【2】 Monneret, C.; Schmidt, F. (CNRS (Centre National de la Recherche Scientifique); Institut Curie); Derivs. of etoposide and analogs, and pharmaceutical compsns. containing them. WO 0335661 . |
| 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) | 64993 | methyl 3,4,5-tris(acetyloxy)-6-{[2-(methylamino)-4-nitrophenyl]oxy}tetrahydro-2H-pyran-2-carboxylate | C20H24N2O12 | 详情 | 详情 | |
| (II) | 64994 | 3,4,5-trihydroxy-6-{[2-(methylamino)-4-nitrophenyl]oxy}tetrahydro-2H-pyran-2-carboxylic acid | C13H16N2O9 | 详情 | 详情 | |
| (III) | 64995 | 3,4,5-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-6-{[2-(methylamino)-4-nitrophenyl]oxy}tetrahydro-2H-pyran-2-carboxylic acid | C31H58N2O9Si3 | 详情 | 详情 | |
| (IV) | 64996 | phenylmethyl 3,4,5-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-6-{[2-(methylamino)-4-nitrophenyl]oxy}tetrahydro-2H-pyran-2-carboxylate | C38H64N2O9Si3 | 详情 | 详情 | |
| (V) | 64997 | phenylmethyl 6-({2-[(chlorocarbonyl)(methyl)amino]-4-nitrophenyl}oxy)-3,4,5-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-carboxylate | C39H63ClN2O10Si3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Reaction of etoposide (VI) with acid chloride (V) produces the carbamate adduct (VII). The silyl protecting groups of (VII) are then removed by treatment with HF-pyridine yielding triol (VIII). Finally, the benzyl ester function of (VIII) is deprotected by transfer hydrogenolysis in the presence of cyclohexadiene and Pd/C. (1,2)
| 【1】 Schmidt, F.; Monneret, C.; Prodrug mono therapy: Synthesis and biological evaluation of an etoposide glucuronide-prodrug. Bioorg Med Chem 2003, 11, 10, 2277. |
| 【2】 Monneret, C.; Schmidt, F. (CNRS (Centre National de la Recherche Scientifique); Institut Curie); Derivs. of etoposide and analogs, and pharmaceutical compsns. containing them. WO 0335661 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 64997 | phenylmethyl 6-({2-[(chlorocarbonyl)(methyl)amino]-4-nitrophenyl}oxy)-3,4,5-tris{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-carboxylate | C39H63ClN2O10Si3 | 详情 | 详情 | |
| (VI) | 13041 | Etoposide; (5R,5aR,8aR,9S)-9-[[(2R,4aR,6R,7R,8R,8aS)-7,8-Dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | 33419-42-0 | C29H32O13 | 详情 | 详情 |
| (VII) | 64998 | benzyl (2S,3R,4S,5R,6S)-6-{2-[{[4-((5R,5aR,8aR,9S)-9-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenoxy]carbonyl}(methyl)amino]-4-nitrophenoxy}-3,4,5-tris{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-carboxylate | C68H94N2O23Si3 | 详情 | 详情 | |
| (VIII) | 64999 | benzyl (2S,3S,4S,5R,6S)-6-{2-[{[4-((5R,5aR,8aR,9S)-9-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenoxy]carbonyl}(methyl)amino]-4-nitrophenoxy}-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate | C50H52N2O23 | 详情 | 详情 |