• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】52391

【品名】3-[(2S,5S)-5-(2-{(2S,4R)-6-[((2S,3R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxy-3-{[(4-methoxybenzyl)oxy]methyl}tetrahydro-2-furanyl)methyl]-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl}ethyl)-4-methylenetetrahydro-2-furanyl]propyl 2,2-dimethylpropanoate

【CA登记号】

【 分 子 式 】C52H90O10Si2

【 分 子 量 】931.4516

【元素组成】C 67.05% H 9.74% O 17.18% Si 6.03%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXVIII)

Homologation of alcohol (XXII) was effected by Swern oxidation to aldehyde (XXIII), which was then converted to the vinyl derivative (XXIV) by Wittig reaction with methylene triphenylphosphorane. Hydroboration of olefin (XXIV), followed by oxidative work-up, furnished alcohol (XXV). This was subjected to a further Swern oxidation to aldehyde (XXVI). Coupling of aldehyde (XXVI) with the known vinyl iodide (XXVII) produced a mixture of pyran derivative (XXVIII) and some uncyclized intermediate. Cyclization to (XXVIII) was completed by subsequent treatment of the reaction mixture with potassium hexamethyldisilazide. The p-methoxybenzyl protecting group of (XXVIII) was removed by oxidative treatment with DDQ. The desired diastereomer (XXIX) was then isolated by column chromatography.

1 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXII) 52384 {5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methanol C30H56O7Si2 详情 详情
(XXIII) 52386 5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furancarbaldehyde C30H54O7Si2 详情 详情
(XXIV) 52387 5-({5-ethenyl-3-(methyloxy)-4-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane; 2-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-5-ethenyl-4-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-3-furanyl methyl ether C31H56O6Si2 详情 详情
(XXV) 52388 2-{5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}-1-ethanol C31H58O7Si2 详情 详情
(XXVI) 52389 2-{5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}acetaldehyde C31H56O7Si2 详情 详情
(XXVII) 52390 3-(5-{6-iodo-5-methyl-3-[(methylsulfonyl)oxy]-6-heptenyl}-4-methylidenetetrahydro-2-furanyl)propyl 2,2-dimethylpropanoate C22H37IO6S 详情 详情
(XXVIII) 52391 3-[(2S,5S)-5-(2-{(2S,4R)-6-[((2S,3R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxy-3-{[(4-methoxybenzyl)oxy]methyl}tetrahydro-2-furanyl)methyl]-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl}ethyl)-4-methylenetetrahydro-2-furanyl]propyl 2,2-dimethylpropanoate C52H90O10Si2 详情 详情
(XXIX) 52392 3-{5-[2-(6-{[5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-(methyloxy)tetrahydro-2-furanyl]methyl}-4-methyl-5-methylidenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylidenetetrahydro-2-furanyl}propyl 2,2-dimethylpropanoate C44H82O9Si2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XXVIII)

Homologation of alcohol (XXII) was effected by Swern oxidation to aldehyde (XXIII), which was then converted to the vinyl derivative (XXIV) by Wittig reaction with methylene triphenylphosphorane. Hydroboration of olefin (XXIV), followed by oxidative work-up, furnished alcohol (XXV). This was subjected to a further Swern oxidation to aldehyde (XXVI). Coupling of aldehyde (XXVI) with the known vinyl iodide (XXVII) produced a mixture of pyran derivative (XXVIII) and some uncyclized intermediate. Cyclization to (XXVIII) was completed by subsequent treatment of the reaction mixture with potassium hexamethyldisilazide. The p-methoxybenzyl protecting group of (XXVIII) was removed by oxidative treatment with DDQ. The desired diastereomer (XXIX) was then isolated by column chromatography.

1 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXII) 52384 {5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methanol C30H56O7Si2 详情 详情
(XXIII) 52386 5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furancarbaldehyde C30H54O7Si2 详情 详情
(XXIV) 52387 5-({5-ethenyl-3-(methyloxy)-4-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane; 2-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-5-ethenyl-4-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-3-furanyl methyl ether C31H56O6Si2 详情 详情
(XXV) 52388 2-{5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}-1-ethanol C31H58O7Si2 详情 详情
(XXVI) 52389 2-{5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}acetaldehyde C31H56O7Si2 详情 详情
(XXVII) 52390 3-(5-{6-iodo-5-methyl-3-[(methylsulfonyl)oxy]-6-heptenyl}-4-methylidenetetrahydro-2-furanyl)propyl 2,2-dimethylpropanoate C22H37IO6S 详情 详情
(XXVIII) 52391 3-[(2S,5S)-5-(2-{(2S,4R)-6-[((2S,3R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxy-3-{[(4-methoxybenzyl)oxy]methyl}tetrahydro-2-furanyl)methyl]-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl}ethyl)-4-methylenetetrahydro-2-furanyl]propyl 2,2-dimethylpropanoate C52H90O10Si2 详情 详情
(XXIX) 52392 3-{5-[2-(6-{[5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-(methyloxy)tetrahydro-2-furanyl]methyl}-4-methyl-5-methylidenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylidenetetrahydro-2-furanyl}propyl 2,2-dimethylpropanoate C44H82O9Si2 详情 详情
Extended Information