ethyl 5-((1R,3S,4R,5S,7S,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-10-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethoxy-1,7,9-trimethyl-9-decenyl)-2,2-dimethyl-1,3-dioxole-4-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】17379

【品名】ethyl 5-((1R,3S,4R,5S,7S,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-10-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethoxy-1,7,9-trimethyl-9-decenyl)-2,2-dimethyl-1,3-dioxole-4-carboxylate

【CA登记号】

【分子式】C₈₂H₁₃₂O₁₅Si₃

【分子量】1442.19758

【元素组成】C 68.29% H 9.23% O 16.64% Si 5.84%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XI)

The diastereoselective reduction of (VII) with NaBH4/CeCl3 in methanol/ethyl ether affords alcohol (VIII), which was methylated with trimethyloxonium tetrafluoroborate in dichloromethane giving the methyl ether (IX). The treatment of (IX) with lithium bis(trimethylsilyl)amide (Li-HMDS) and Mg(HMDS)2 causes enolization and ring opening affording alcohol (X), which was protected with tert-butyldimethylsilyl triflate yielding the fully silylated compound (XI). The hydrolysis of the ester group of (XI) with NaOH, followed by a selective elimination of the triethylsilyl group with trifluoroacetic acid and esterification of the resulting alcohol with piperidine-2(S)-carboxylic acid (XII) by means of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP) afforded ester (XIII).

参考文献中间体

合成目标

【1】 Liu, L.B.; Roper, T.D.; Gleason, J.L.; Ireland, R.E.; Total synthesis of FK-506. 2. Completion of the synthesis. Tetrahedron 1997, 53, 39, 13257.
【2】 Liu, L.B.; Roper, T.D.; Ireland, R.E.; Total synthesis of FK-506. 1. Construction of the C16-C34 fragment. Tetrahedron 1997, 53, 39, 13221.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	17375	ethyl (4R,5S,7S,8S,10R)-7-((3S,5E)-6-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethyl-5-hexenoyl)-8-methoxy-2,2,10-trimethyl-1,3,6-trioxaspiro[4.5]decane-4-carboxylate		C₇₅H₁₁₄O₁₅Si₂	详情	详情
(VIII)	17376	ethyl (4R,5S,7R,8S,10R)-7-((1S,3S,5E)-6-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-1-hydroxy-3,5-dimethyl-5-hexenyl)-8-methoxy-2,2,10-trimethyl-1,3,6-trioxaspiro[4.5]decane-4-carboxylate		C₇₅H₁₁₆O₁₅Si₂	详情	详情
(IX)	17377	ethyl (4R,5S,7R,8S,10R)-7-((1S,3S,5E)-6-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-1-methoxy-3,5-dimethyl-5-hexenyl)-8-methoxy-2,2,10-trimethyl-1,3,6-trioxaspiro[4.5]decane-4-carboxylate		C₇₆H₁₁₈O₁₅Si₂	详情	详情
(X)	17378	ethyl 5-((1R,3S,4R,5S,7S,9E)-10-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-4-hydroxy-3,5-dimethoxy-1,7,9-trimethyl-9-decenyl)-2,2-dimethyl-1,3-dioxole-4-carboxylate		C₇₆H₁₁₈O₁₅Si₂	详情	详情
(XI)	17379	ethyl 5-((1R,3S,4R,5S,7S,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-10-[4-[(1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[(triethylsilyl)oxy]-3-butenyl]-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethoxy-1,7,9-trimethyl-9-decenyl)-2,2-dimethyl-1,3-dioxole-4-carboxylate		C₈₂H₁₃₂O₁₅Si₃	详情	详情
(XII)	17380	(2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid	3105-95-1	C₆H₁₁NO₂	详情	详情
(XIII)	17381	5-((1R,3S,4R,5S,7S,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-10-[4-((1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[[(2S)piperidinylcarbonyl]oxy]-3-butenyl)-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethoxy-1,7,9-trimethyl-9-decenyl)-2,2-dimethyl-1,3-dioxole-4-carboxylic acid		C₈₀H₁₂₃NO₁₆Si₂	详情	详情

Extended Information