tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R)-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]a -Drug Synthesis Database

【结构式】

【分子编号】42411

【品名】tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R)-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]a

【CA登记号】

【分子式】C₅₃H₇₄O₁₄Si

【分子量】963.24766

【元素组成】C 66.09% H 7.74% O 23.25% Si 2.92%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(L)

Synthesis of intermediate (L): The condensation of aldehyde intermediate (XLIII) with iodovinyl intermediate (XXXIII) by means of NiCl2/CrCl2 bispyridinyl ligand in THF, followed by a treatment with DMP, gives the adduct (XLIV), which is treated with PPTS to yield the bis spiroketal (XLV) with undesired configuration at the new stereocenter. The treatment of (XLV) with HF/pyridine in acetonitrile gives rise to a desilylation of the TBDMS group with concomitant isomerization of the new stereocenter yielding a separable mixture of two diastereomers (XLVI) and (XLVII). Compound (XLVII) has the desired configuration, and (XLVI) can be recovered by isomerizing it again to the starting diastereomeric mixture. The silylation of (XLVII) with TBDMS-OTf, followed by selective monodesilylation of the primary OH group with HF/pyridine in THF, gives the ethanol derivative (XLVIII), which is oxidized with tetrapropylammonium perruthenate (TPAP) and NaClO2 and silylated with TBDPSCl to yield the silyl ester (XLIX). Finally, this compound is selectively deprotected with DDQ and oxidized with DMP to afford the desired aldehydic intermediate (L).

参考文献中间体

合成目标

【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXXIII)	42395	tert-butyl(dimethyl)silyl (2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl ether; tert-butyl[[(2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl]oxy]dimethylsilane	C₂₈H₄₇IO₇Si	详情	详情
(XLIII)	42404	2-((2S,4S,6S,8S,10S)-4-(acetoxy)-8-[2-[(1R,2S,3S)-2-(acetoxy)-1,3-dimethyl-4-oxobutyl]-2-propenyl]-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl)ethyl 2-methoxyacetate	C₂₈H₄₄O₁₁	详情	详情
(XLIV)	42405	2-((2S,4S,6R,8S,10S)-4-(acetoxy)-8-[(3R,4S,5S,7E,10S)-4-(acetoxy)-11-[(2R,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-2-yl]-10-methoxy-3,5-dimethyl-2-methylene-6-oxo-7-undeceny	C₅₆H₉₀O₁₈Si	详情	详情
(XLV)	42406	(2S,4S,6S,8S,10S)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R,10S)-10-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-2-(2-hydrox	C₅₂H₈₄O₁₆Si	详情	详情
(XLVI)	42407	(1S,2R)-3-[[(2S,4S,6S,8S,10S)-10-(acetoxy)-4-hydroxy-8-(2-hydroxyethyl)-4-methyl-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-1-[(1S)-3-[(2S,4S,6R,8R,10S)-10-hydroxy-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1-met	C₄₆H₇₀O₁₆	详情	详情
(XLVII)	42408	(1S,2R)-3-[[(2S,4S,6S,8S,10S)-10-(acetoxy)-4-hydroxy-8-(2-hydroxyethyl)-4-methyl-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-1-[(1S)-3-[(2S,4S,6S,8R,10S)-10-hydroxy-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1-met	C₄₆H₇₀O₁₆	详情	详情
(XLVIII)	42409	(2S,4S,6S,8S,10S)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6R,8R,10S)-10-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-2-(2-hydrox	C₅₂H₈₄O₁₆Si	详情	详情
(XLIX)	42410	tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6R,8R,10S)-10-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-8-([[(4-methoxybenzyl)oxy]methoxy]methyl)-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-ox	C₆₈H₁₀₀O₁₇Si₂	详情	详情
(L)	42411	tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R)-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]a	C₅₃H₇₄O₁₄Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(L)

Synthesis of the target 213774: The Wittig condensation of the intermediate aldehyde (L) with the intermediate phosphonium iodide (LXXXV) by means of LDA in THF/HMPA gives the adduct (LXXXVI). Cleavage of the Mpm protecting groups and simultaneous hydrolysis of the methyl ketal group with DDQ, followed by KF-induced elimination of the silyl ester protecting group and macrolactonization under Yamaguchi conditions, afforded macrolactone (LXXXVII). Finally, this compound is desilylated with HF/pyridine in THF.

参考文献中间体

合成目标

【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(L)	42411	tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R)-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]a	C₅₃H₇₄O₁₄Si	详情	详情
(LXXXV)	42445	(4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox	C₇₃H₁₀₃ClIO₁₀PSi₂	详情	详情
(LXXXVI)	42446		C₁₁₄H₁₇₅ClO₂₄Si₄	详情	详情
(LXXXVII)	42447		C₈₁H₁₃₇ClO₂₁Si₃	详情	详情

Extended Information