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【结 构 式】 
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【分子编号】11497 【品名】(3S,4S,5S,7S,8R,12S,14S,15R,16S,18R,26aS)-8-Allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-20-[(2,4-dimethoxybenzyl)oxy]-14,16-dimethoxy-7-[(4-methoxybenzyl)oxy]-3-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-4,10,12,18-tetramethyl-5-[(triisopropylsilyl)oxy]-5,6,7,8,11,12,13,14,15,16,17,18,24,25,26,26a-hexadecahydro-3H-pyrido[2,1-c][1,4]oxazacyclotricosine-1,19,21(4H,20H,23H)-trione 【CA登记号】 |
【 分 子 式 】C85H145NO15Si3 【 分 子 量 】1505.34054 【元素组成】C 67.82% H 9.71% N 0.93% O 15.94% Si 5.6% |
合成路线1
该中间体在本合成路线中的序号：(LVIII)The cyclization of (LVI) by means of N-methyl-2-chloropyridinium iodide and triethylamine yields the macrocyclic lactam (LVII), which is selectively deprotected with trifluoroacetic acid in THF - water and oxidized with DMP in dichloromethane affording the beta-keto lactam (LVIII). Selective deprotection of (LVIII) with DDQ in dichloromethane - tert-butyl alcohol gives the diol (LIX), which is then oxidized with DMP in dichloromethane yielding the silylated FK-506 (LX). Finally, this compound is deprotected by treatment with HF in acetonitrile.
| 【1】 Smith, D.B.; Schreiber, S.L.; Ragan, J.A.; Uehling, D.E.; Nakatsuka, M.; Sammakia, T.; Total synthesis of FK506 and an FKBP probe reagent, (C8,C9-13C2)-FK5. J Am Chem Soc 1990, 112, 14, 5583. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LVI) | 11495 | (4R,6S,7R,8S,10S,12E,14R,15S,17S,18S,19S,20E)-14-Allyl-7-[[tert-butyl(dimethyl)silyl]oxy]-2-[(2,4-dimethoxybenzyl)oxy]-6,8-dimethoxy-15-[(4-methoxybenzyl)oxy]-21-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,10,12,18,20-pentamethyl-19-[[(2S)piperidinylcarbonyl]oxy]-3-[(triethylsilyl)oxy]-17-[(triisopropylsilyl)oxy]-12,20-henicosadienoic acid | C91H163NO16Si4 | 详情 | 详情 | |
| (LVII) | 11496 | (3S,4S,5S,8R,12S,14S,15R,16S,18R,26aS)-8-Allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-20-[(2,4-dimethoxybenzyl)oxy]-14,16-dimethoxy-7-[(4-methoxybenzyl)oxy]-3-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-4,10,12,18-tetramethyl-19-[(triethylsilyl)oxy]-5-[(triisopropylsilyl)oxy]-5,6,7,8,11,12,13,14,15,16,17,18,19,20,24,25,26,26a-octadecahydro-3H-pyrido[2,1-c][1,4]oxazacyclotricosine-1,21(4H,23H)-dione | C91H161NO15Si4 | 详情 | 详情 | |
| (LVIII) | 11497 | (3S,4S,5S,7S,8R,12S,14S,15R,16S,18R,26aS)-8-Allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-20-[(2,4-dimethoxybenzyl)oxy]-14,16-dimethoxy-7-[(4-methoxybenzyl)oxy]-3-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-4,10,12,18-tetramethyl-5-[(triisopropylsilyl)oxy]-5,6,7,8,11,12,13,14,15,16,17,18,24,25,26,26a-hexadecahydro-3H-pyrido[2,1-c][1,4]oxazacyclotricosine-1,19,21(4H,20H,23H)-trione | C85H145NO15Si3 | 详情 | 详情 | |
| (LIX) | 11498 | (3S,4S,5S,7S,8R,12S,14S,15R,16S,18R,26aS)-8-Allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-7,20-dihydroxy-14,16-dimethoxy-3-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-4,10,12,18-tetramethyl-5-[(triisopropylsilyl)oxy]-5,6,7,8,11,12,13,14,15,16,17,18,24,25,26,26a-hexadecahydro-3H-pyrido[2,1-c][1,4]oxazacyclotricosine-1,19,21(4H,20H,23H)-trione | C68H127NO12Si3 | 详情 | 详情 | |
| (LX) | 11499 | (3S,4S,5S,8R,12S,14S,15R,16S,18R,26aS)-8-Allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-14,16-dimethoxy-3-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-4,10,12,18-tetramethyl-5-[(triisopropylsilyl)oxy]-5,6,11,12,13,14,15,16,17,18,24,25,26,26a-tetradecahydro-3H-pyrido[2,1-c][1,4]oxazacyclotricosine-1,7,19,20,21(4H,8H,23H)-pentone | C68H123NO12Si3 | 详情 | 详情 |