[(2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl](triphenyl)phosphonium iodide -Drug Synthesis Database

【结构式】

【分子编号】42684

【品名】[(2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl](triphenyl)phosphonium iodide

【CA登记号】

【分子式】C₆₀H₉₀IO₄PSi₂

【分子量】1089.421432

【元素组成】C 66.15% H 8.33% I 11.65% O 5.87% P 2.84% Si 5.16%

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：(XXXIV)

The target compound has been obtained as follows: The reaction of intermediate iodo derivative (XV) with ZnCl2 and BuLi gives the organozinc compound (XXVI), which is condensed with intermediate iodo derivative (XVIII) by means of Pd(PPh3)4, yielding the adduct (XXVII). The selective deprotection of the Pmb group of (XXVII) with DDQ, followed by reprotection with Tr-Cl, affords the suitably protected adduct (XXVIII). Cleaving of the cyclic ketal group of (XXVIII) with DIBAL provides the primary alcohol (XXIX), which is oxidized with DMP, giving the aldehyde (XXX). The condensation of (XXX) with the titanium derivative (XXXI) yields the adduct (XXXII), which is selectively deprotected at the trityl group with chloro-catecholborane to afford the primary alcohol (XXXIII). The reaction of (XXXIII) with PPh3 , I2 and DIEA furnishes the phosphonium iodide (XXXIV).

参考文献中间体

合成目标

【1】 Smith, A.B. III; et al.; Evolution of a gram-scale synthesis of (+)-discodermolide. J Am Chem Soc 2000, 122, 36, 8654.
【2】 Smith, A.B. III; et al.; Gram-scale synthesis of (+)-discodermolide. Org Lett 1999, 1, 11, 1823.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XV)	42665	tert-butyl(dimethyl)silyl (1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl ether; tert-butyl[((1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl)oxy]dimethylsilane	C₂₄H₄₁IO₄Si	详情	详情
(XVIII)	42668	tert-butyl(dimethyl)silyl (1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl ether; tert-butyl[((1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl)oxy]dimethylsilane	C₂₃H₃₉IO₃Si	详情	详情
(XXVI)	42676	tert-butyl[(2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methylpentyl]zinc	C₂₈H₅₀O₄SiZn	详情	详情
(XXVII)	42677	(5R,6S,7Z,10S,11R)-5-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-11-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disila-7-pentadecene; 4-((4S,5S)-4-[(1R,2R,3S,5Z,7S,8R,9S)-2,8-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(4-methoxybenzyl)oxy]-1,3,5,7,9-pentamethyl-5-decenyl]-5-methyl-1,3-dioxan-2-yl)phenyl methyl ether	C₄₇H₈₀O₇Si₂	详情	详情
(XXVIII)	42678	(5R,6S,7Z,10S,11R)-11-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-2-(trityloxy)ethyl]-4,12-dioxa-3,13-disila-7-pentadecene; (2S,3R,4S,5Z,8S,9R,10R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2,4,6,8-tetramethyl-5-undecenyl trityl ether	C₅₈H₈₆O₆Si₂	详情	详情
(XXIX)	42679	(2S,3S,4R,5R,6S,8Z,10S,11R,12S)-5,11-bis[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-13-(trityloxy)-8-tridecen-1-ol	C₅₈H₈₈O₆Si₂	详情	详情
(XXX)	42680	(2R,3R,4R,5R,6S,8Z,10S,11R,12S)-5,11-bis[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-13-(trityloxy)-8-tridecenal	C₅₈H₈₆O₆Si₂	详情	详情
(XXXI)	42681		C₃₉H₃₄LiO₄PTi	详情	详情
(XXXII)	42682	(2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl trityl ether; (5R,6S,7Z,10S,11R)-11-[(1R,2S,3S,4Z)-2-[(4-methoxybenzyl)oxy]-1,3-dimethyl-4,6-heptadienyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-2-(trityloxy)ethyl]-4,12-dioxa-3,13-disila-7-pentadecene	C₆₁H₉₀O₅Si₂	详情	详情
(XXXIII)	42683	(2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrien-1-ol	C₄₂H₇₆O₅Si₂	详情	详情
(XXXIV)	42684	[(2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl](triphenyl)phosphonium iodide	C₆₀H₉₀IO₄PSi₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXIV)

The condensation of (XXXIV) with the intermediate aldehyde (XXV) by means of NaHMDS gives the fully protected lactone derivative (XXXV), which is selectively deprotected at the Pmb group with DDQ, yielding the secondary alcohol (XXXVI). The reaction of (XXXVI) with trichloroacetyl isocyanate and Al2O3 affords the corresponding carbamate (XXXVII), which is finally desilylated with HCl in methanol.

参考文献中间体

合成目标

【1】 Smith, A.B. III; et al.; Evolution of a gram-scale synthesis of (+)-discodermolide. J Am Chem Soc 2000, 122, 36, 8654.
【2】 Smith, A.B. III; et al.; Gram-scale synthesis of (+)-discodermolide. Org Lett 1999, 1, 11, 1823.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXV)	42675	(2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(2S,3R,4S,5R)-4-methoxy-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl]propanal	C₁₇H₃₂O₅Si	详情	详情
(XXXIV)	42684	[(2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl](triphenyl)phosphonium iodide	C₆₀H₉₀IO₄PSi₂	详情	详情
(XXXV)	42685	(3R,4S,5R,6S)-4-methoxy-3,5-dimethyl-6-[(2S,3Z,5S,6S,7S,8Z,11S,12R,13R,14S,15S,16Z)-2,6,12-tris[[tert-butyl(dimethyl)silyl]oxy]-14-[(4-methoxybenzyl)oxy]-5,7,9,11,13,15-hexamethyl-3,8,16,18-nonadecatetraenyl]tetrahydro-2H-pyran-2-one	C₅₉H₁₀₆O₈Si₃	详情	详情
(XXXVI)	42686	(3R,4S,5R,6S)-4-methoxy-3,5-dimethyl-6-((2S,3Z,5S,6S,7S,8Z,11S,12R,13R,14S,15S,16Z)-2,6,12-tris[[tert-butyl(dimethyl)silyl]oxy]-14-hydroxy-5,7,9,11,13,15-hexamethyl-3,8,16,18-nonadecatetraenyl)tetrahydro-2H-pyran-2-one	C₅₁H₉₈O₇Si₃	详情	详情
(XXXVII)	42687	(1S,2R,3R,4S,6Z,8S,9S,10S,11Z,13S)-3,9,13-tris[[tert-butyl(dimethyl)silyl]oxy]-14-[(2S,3R,4S,5R)-4-methoxy-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl]-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-6,11-tetradecadienyl carbamate	C₅₂H₉₉NO₈Si₃	详情	详情

Extended Information