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 -Drug Synthesis Database

【结构式】

【分子编号】42404

【品名】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

【CA登记号】

【分子式】C₂₈H₄₄O₁₁

【分子量】556.65076

【元素组成】C 60.42% H 7.97% O 31.62%

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：(XLIII)

Synthesis of intermediate (XLIII): The condensation of dithiane intermediate (VII) with epoxide intermediate (XIV) by means of NaOtBu and n-BuLi gives alcohol (XXXIV), which is converted into epoxide (XXXV) by treatment with pyridinium p-toluenesulfonate (PPTS), NaH and tosyl-imidazole in THF. The condensation of (XXXV) with intermediate iodovinyl compound (XX) by means of n-BuLi in THF yields the diol (XXXVI), which is treated with CaCO3 and NIS to afford the spiroketal (XXXVII). The monoacylation of (XXXVIII) with methoxyacetyl chloride (XXXVIII) and LiNH2, followed by cleavage of the cyclohexylidene ketal with PPTS, provides the triol (XXXIX), which is selectively silylated at the primary OH group with TBDMSCl to give the silyl ether (LX). The acylation of the two secondary OH groups of (LX) with Ac2O and DMAP yields the diacetate (XLI), which is desilylated with HF and pyridine in acetonitrile afford the primary alcohol (XLII). Finally, this compound is oxidized with DMP in dichloromethane to furnish the desired intermediate aldehyde (XLIII).

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	CAS号	分子式	供应商	用于合成
(VII)	42373	benzyl (3S,5S)-3,5-bis[[tert-butyl(diphenyl)silyl]oxy]-6-(1,3-dithian-2-yl)hexyl ether; (5S,7S)-5-[2-(benzyloxy)ethyl]-7-(1,3-dithian-2-ylmethyl)-2,2,10,10-tetramethyl-3,3,9,9-tetraphenyl-4,8-dioxa-3,9-disilaundecane		C₄₉H₆₂O₃S₂Si₂	详情	详情
(XIV)	42380	tert-butyl(dimethyl)silyl (1R)-2-(2-ethoxyethoxy)-1-[[(2S)-2-methyloxiranyl]methyl]ethyl ether; (5R)-2,2,3,3-tetramethyl-5-[[(2S)-2-methyloxiranyl]methyl]-4,7,10-trioxa-3-siladodecane		C₁₆H₃₄O₄Si	详情	详情
(XX)	42386	(2R,3R)-2-[(1S)-2-iodo-1-methyl-2-propenyl]-3-methyl-1,5-dioxaspiro[5.5]undecane		C₁₄H₂₃IO₂	详情	详情
(XXXIV)	42396	(2S,4R)-1-[2-((2S,4S)-6-(benzyloxy)-2,4-bis[[tert-butyl(diphenyl)silyl]oxy]hexyl)-1,3-dithian-2-yl]-4-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-ethoxyethoxy)-2-methyl-2-pentanol		C₆₅H₉₆O₇S₂Si₃	详情	详情
(XXXV)	42397	(2S)-1-[2-((2S,4S)-6-(benzyloxy)-2,4-bis[[tert-butyl(diphenyl)silyl]oxy]hexyl)-1,3-dithian-2-yl]-2-methyl-3-[(2R)oxiranyl]-2-propanol		C₅₅H₇₂O₅S₂Si₂	详情	详情
(XXXVI)	42398	(2S,4S)-1-[2-((2S,4S)-6-(benzyloxy)-2,4-bis[[tert-butyl(diphenyl)silyl]oxy]hexyl)-1,3-dithian-2-yl]-2-methyl-6-[(1R)-1-[(2S,3R)-3-methyl-1,5-dioxaspiro[5.5]undec-2-yl]ethyl]-6-heptene-2,4-diol		C₆₉H₉₆O₇S₂Si₂	详情	详情
(XXXVII)	42399	(2S,4S,6S,8S,10S)-8-[2-(benzyloxy)ethyl]-4-methyl-2-(2-[(1R)-1-[(2S,3R)-3-methyl-1,5-dioxaspiro[5.5]undec-2-yl]ethyl]-2-propenyl)-1,7-dioxaspiro[5.5]undecane-4,10-diol		C₃₄H₅₂O₇	详情	详情
(XXXVIII)	13429	2-Methoxyacetyl chloride; Methoxyacetyl chloride	38870-89-2	C₃H₅ClO₂	详情	详情
(XXXIX)	42400	2-((2S,4S,6S,8S,10S)-8-[2-[(1R,2S,3R)-2,4-dihydroxy-1,3-dimethylbutyl]-2-propenyl]-4,10-dihydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl)ethyl 2-methoxyacetate		C₂₄H₄₂O₉	详情	详情
(XL)	42401	2-[(2S,4S,8S,10S)-8-[2-((1R,2S,3R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-hydroxy-1,3-dimethylbutyl)-2-propenyl]-4,10-dihydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]ethyl 2-methoxyacetate		C₃₀H₅₆O₉Si	详情	详情
(XLI)	42402	2-[(2S,4S,8S,10S)-4-(acetoxy)-8-[2-((1R,2S,3R)-2-(acetoxy)-4-[[tert-butyl(dimethyl)silyl]oxy]-1,3-dimethylbutyl)-2-propenyl]-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]ethyl 2-methoxyacetate		C₃₄H₆₀O₁₁Si	详情	详情
(XLII)	42403	2-((2S,4S,6S,8S,10S)-4-(acetoxy)-8-[2-[(1R,2S,3R)-2-(acetoxy)-4-hydroxy-1,3-dimethylbutyl]-2-propenyl]-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl)ethyl 2-methoxyacetate		C₂₈H₄₆O₁₁	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

合成路线2

该中间体在本合成路线中的序号：(XLIII)

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

Extended Information