Yaozh News Star Club Edu TOP100 Customer Service APP
Iphone Download Android Download
  • English
  • 简体中文
Login Register
Search
Current Location： Home > Feedback Help Print

【结 构 式】

【分子编号】44441

【品名】(3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-pentanone

【CA登记号】

【 分 子 式 】C17H38O3Si2

【 分 子 量 】346.65792

【元素组成】C 58.9% H 11.05% O 13.85% Si 16.2%
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：(X)

The silylation of 2-methyl-5-(tert-butyldimethylsilyloxy)-1-penten-3(s)-ol (VIII) with Tbdms-Cl and imidazole in DMF gives the disilylated compound (IX), which is treated with ozone and PPh3 in dichloromethane to yield the 2-pentanone (X). The condensation of (X) with phosphonate (XI) by means of BuLi in THF yields the fully silylated diol (XII), which is selectively monodesilylated with HF in acetonitrile to afford the primary alcohol (XIII). The oxidation of (XIII) with DMP in dichloromethane affords the aldehyde (XIV), which is methylenated with the phosphonium salt (XV) and NaNH2 in THF to provide the silylated hexadienol (XVI). The reaction of (XVI) with TBAF in THF gives the free secondary alcohol (XVII), which is esterified with the intermediate tridecenoic acid (VII) by means of DCC and DMAP in dichloromethane, yielding the ester (XVIII). Ring-closing metathesis of (XVIII), catalyzed by a Ru catalyst, affords the macrolactone (XIX), which is desilylated by means of HF in acetonitrile to furnish the dihydroxymacrolactone (XX). Finally, the double bond of (XX) is epoxidated with dimethyldioxirane (DMDO) in dichloromethane to provide the target epothilone A.

参考文献 中间体
合成目标
【1】 Schinzer, D.; et al.; Total synthesis of (-)-epothilone A. Angew Chem. Int Ed Engl 1997, 36, 5, 523.
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) 44438 (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid C29H58O5Si2 详情 详情
(VIII) 44439 (3S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-penten-3-ol C12H26O2Si 详情 详情
(IX) 44440 (5S)-5-isopropenyl-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecane; tert-butyl(dimethyl)silyl (1S)-1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-methyl-2-propenyl ether C18H40O2Si2 详情 详情
(X) 44441 (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-pentanone C17H38O3Si2 详情 详情
(XI) 44442 diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate C9H16NO3PS 详情 详情
(XII) 44443 tert-butyl(dimethyl)silyl (1S,2E)-1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-pentenyl)-2-methyl-1,3-thiazole C22H43NO2SSi2 详情 详情
(XIII) 40821 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol C16H29NO2SSi 详情 详情
(XIV) 40822 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal C16H27NO2SSi 详情 详情
(XV) 30484 Methyl(triphenyl)phosphonium bromide 1779-49-3 C19H18BrP 详情 详情
(XVI) 44444 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether C17H29NOSSi 详情 详情
(XVII) 43171 (1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol C11H15NOS 详情 详情
(XVIII) 44445 (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoate C40H71NO5SSi2 详情 详情
(XIX) 44446 (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione C38H67NO5SSi2 详情 详情
(XX) 44447 (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione C26H39NO5S 详情 详情

合成路线2

该中间体在本合成路线中的序号：(X)

The silylation of 2-methyl-5-(tert-butyldimethylsilyloxy)-1-penten-3(s)-ol (VIII) with Tbdms-Cl and imidazole in DMF gives the disilylated compound (IX), which is treated with ozone and PPh3 in dichloromethane to yield the 2-pentanone (X). The condensation of (X) with phosphonate (XI) by means of BuLi in THF yields the fully silylated diol (XII), which is selectively monodesilylated with HF in acetonitrile to afford the primary alcohol (XIII). The oxidation of (XIII) with DMP in dichloromethane affords the aldehyde (XIV), which is methylenated with the phosphonium salt (XV) and Na-NH2 in THF to provide the silylated hexadienol (XVI). The reaction of (XVI) with TBAF in THF gives the free secondary alcohol (XVII), which is esterified with the intermediate tridecenoic acid (VII) by means of DCC and DMAP in dichloromethane yielding the ester (XVIII). Ring-closing metathesis of (XVIII), catalyzed by a Ru catalyst, affords the macrolactone (XIX), which is finally desilylated by means of HF in acetonitrile to furnish the target epothilone C.

参考文献 中间体
合成目标
【1】 Schinzer, D.; et al.; Total synthesis of (-)-epothilone A. Angew Chem. Int Ed Engl 1997, 36, 5, 523.
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) 44438 (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid C29H58O5Si2 详情 详情
(VIII) 44439 (3S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-penten-3-ol C12H26O2Si 详情 详情
(IX) 44440 (5S)-5-isopropenyl-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecane; tert-butyl(dimethyl)silyl (1S)-1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-methyl-2-propenyl ether C18H40O2Si2 详情 详情
(X) 44441 (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-pentanone C17H38O3Si2 详情 详情
(XI) 44442 diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate C9H16NO3PS 详情 详情
(XII) 44443 tert-butyl(dimethyl)silyl (1S,2E)-1-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-pentenyl)-2-methyl-1,3-thiazole C22H43NO2SSi2 详情 详情
(XIII) 40821 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol C16H29NO2SSi 详情 详情
(XIV) 40822 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal C16H27NO2SSi 详情 详情
(XV) 30484 Methyl(triphenyl)phosphonium bromide 1779-49-3 C19H18BrP 详情 详情
(XVI) 44444 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether C17H29NOSSi 详情 详情
(XVII) 43171 (1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol C11H15NOS 详情 详情
(XVIII) 44445 (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoate C40H71NO5SSi2 详情 详情
(XIX) 44446 (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione C38H67NO5SSi2 详情 详情
Extended Information