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 -Drug Synthesis Database

【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 合成路线2

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.

参考文献中间体

合成目标

【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	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)

参考文献中间体

合成目标

【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	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