【结 构 式】 |
【分子编号】11557 【品名】2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-12,14-dimethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-17-oxo-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate 【CA登记号】 |
【 分 子 式 】C77H149NO12Si4 【 分 子 量 】1393.3716 【元素组成】C 66.37% H 10.78% N 1.01% O 13.78% Si 8.06% |
合成路线1
该中间体在本合成路线中的序号:(LVIII)3) Coupling and cyclization process.- The condensation of the diphenylphosphine derivative (XXIV) with aldehyde (LI) by means of butyllithium in THF gives the hydroxy phosphine derivative (LII), which is treated with potassium hexamethyldisylazane (KHMDS) to afford dithiane (LIII). Partial desilylation of (LIII) with THF - water - trifluoroacetic acid gives alcohol (LIV), which is condensed with N-tert-butoxycarbonylpiperidine-2(S)-carboxylic acid (LV) by means of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine in dichloromethane to yield the ester (LVI). Elimination of the dithiane ring of (LVI) with N-chlorosuccinimide and silver nitrate in anhydrous methanol affords the dimethyl acetal (LVII), which is hydrolyzed to the corresponding aldehyde (LVIII) with acetic acid. The condensation of (LVIII) with 4(S)-benzyl-3-[2-(4-methoxybenzyloxy)acetyl]oxazolidin-2-one (LIX) by means of dibutylboron trifluoromethylsulfonate in toluene gives the oxazolidone derivative (LX).
【1】 Jones, T.K.; Askin, D.; Mills, S.G.; Reamer, R.A.; Desmond, R.; Volante, R.P.; Tschaen, D.M.; Shinkai, I. (Merck & Co., Inc.); Process for synthesis of FK-506 and tricarbonyl intermediates. EP 0378318; JP 1990233643 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXIV) | 11523 | (3R,5S,6R,7S,9R)-6-[[tert-Butyl(dimethyl)silyl]oxy]-9-(1,3-dithian-2-yl)-5,7-dimethoxy-1,3-dimethyldecyl(diphenyl)phosphine oxide; [(3R,5S,6R,7S,9R)-6-[[tert-Butyl(dimethyl)silyl]oxy]-9-(1,3-dithian-2-yl)-5,7-dimethoxy-1,3-dimethyldecyl](oxo)diphenylphosphorane | C36H59O4PS2Si | 详情 | 详情 | |
(LI) | 11550 | (2S,3S,5S,6S,7S,8E)-2-Allyl-3-[[tert-butyl(dimethyl)silyl]oxy]-9-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-6,8-dimethyl-7-[(triethylsilyl)oxy]-5-[(triisopropylsilyl)oxy]-8-nonenal | C51H104O6Si4 | 详情 | 详情 | |
(LII) | 11553 | (1E,3S,4S,5S,7S,8R,9E,12S,14S,15R,16S,18R)-8-Allyl-7,15-bis[[tert-butyl(dimethyl)silyl]oxy]-18-(1,3-dithian-2-yl)-14,16-dimethoxy-1-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-2,4,10,12-tetramethyl-5-[(triisopropylsilyl)oxy]-1,9-nonadecadien-3-ol | C69H138O8S2Si4 | 详情 | 详情 | |
(LIII) | 11552 | (5R,6S,8S,10E,12R,13S,15S,16S,17S)-12-Allyl-13-[[tert-butyl(dimethyl)silyl]oxy]-5-[(1S,3R)-3-(1,3-dithian-2-yl)-1-methoxybutyl]-19,19-diethyl-6-methoxy-17-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,2,3,3,8,10,16-heptamethyl-15-[(triisopropylsilyl)oxy]-4,18-dioxa-3,19-disila-10-henicosene; (1S,3S,4R,5E,8S,10S,11R,12S,14R)-4-Allyl-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-14-(1,3-dithian-2-yl)-10,12-dimethoxy-1-[(1S,2S,3E)-4-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-6,8-dimethyl-5-pentadecenyl triisopropylsilyl ether | C75H152O8S2Si5 | 详情 | 详情 | |
(LIV) | 11551 | (5R,6S,8R,12R,13S,15S,16S,17S)-12-allyl-13-[[tert-butyl(dimethyl)silyl]oxy]-9-(diphenylphosphoryl)-5-[(1S,3R)-3-(1,3-dithian-2-yl)-1-methoxybutyl]-19,19-diethyl-6-methoxy-17-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methyl | C87H163O10PS2Si5 | 详情 | 详情 | |
(LV) | 11487 | (2S)-1-(tert-Butoxycarbonyl)hexahydro-2-pyridinecarboxylic acid | C11H19NO4 | 详情 | 详情 | |
(LVI) | 11555 | 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-16-(1,3-dithian-2-yl)-12,14-dimethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10-trimethyl-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate | C80H155NO11S2Si4 | 详情 | 详情 | |
(LVII) | 11556 | 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-12,14,17,17-tetramethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate | C79H155NO13Si4 | 详情 | 详情 | |
(LVIII) | 11557 | 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R)-6-allyl-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-12,14-dimethoxy-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-17-oxo-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate | C77H149NO12Si4 | 详情 | 详情 | |
(LIX) | 11558 | (4S)-4-Benzyl-3-[3-(4-methoxyphenyl)propanoyl]-1,3-oxazolidin-2-one | C20H21NO4 | 详情 | 详情 | |
(LX) | 11559 | 2-[(1S,2S,3S,5S,6R,7E,10S,12S,13R,14S,16R,17R)-6-allyl-19-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-5,13-bis[[tert-butyl(dimethyl)silyl]oxy]-17-hydroxy-12,14-dimethoxy-18-[(4-methoxybenzyl)oxy]-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-19-oxo-3-[(triisopropylsilyl)oxy]-7-nonadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate | C97H170N2O17Si4 | 详情 | 详情 |