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【结 构 式】 
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【分子编号】35882 【品名】(E,4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-((2S,3S,4S,5S,6R,9S,11S)-4-[[tert-butyl(dimethyl)silyl]oxy]-9-ethyl-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undec-2-yl)-4-methyl-2-hexenal 【CA登记号】 |
【 分 子 式 】C33H63NO5Si2 【 分 子 量 】610.03796 【元素组成】C 64.97% H 10.41% N 2.3% O 13.11% Si 9.21% |
合成路线1
该中间体在本合成路线中的序号：(XXV)The regiocontrolled condensation of (spirolactam (XVII) with the chiral borane (+)(Z)-crotyl-diisopinocampheylborane (XX) in THF gives the diol (XXI), which is silylated with TBDMS-OTf and lutidine in dichloromethane yielding the bis(silyloxy) compound (XXII). The ozonolysis of the terminal double bond of (XXII) with O3 in dichloromethane affords the aldehyde (XXIII), which is condensed with the silyl aldimine (XXIV) by means of LDA in THF giving the unsaturated aldehyde (XXV). Hydrogenation of the double bond of (XXV) yields aldehyde (XXVI), which is condensed with the diazo phosphonate (XXVII) by means of K2CO3 in methanol providing the terminal acetylenic compound (XXVIII). The reaction of (XXVIII) with TBAF in THF gives the desilylated acetylenic compound (XXIX), which is brominated with NBS and AgNO3 in acetone yielding the omega-bromoacetylenic compound (XXX). Finally, this compound is treated with tributyltin hydride, Pd2(dba)3 and PPh3 in chloroform to afford the desired tributyl stannane intermediate (I).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the novel immunosuppressant Sanglifehrin A. J Am Chem Soc 2000, 122, 16, 3830. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 35874 | (2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-2-[(2S,3S,6E)-2-hydroxy-3-methyl-7-(tributylstannyl)-6-heptenyl]-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one | C34H65NO4Sn | 详情 | 详情 | |
| (XVII) | 32424 | 2-[(2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undec-2-yl]acetaldehyde | C16H27NO4 | 详情 | 详情 | |
| (XXI) | 35879 | (2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-2-[(2S,3S)-2-hydroxy-3-methyl-4-pentenyl]-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one | C20H35NO4 | 详情 | 详情 | |
| (XXII) | 35880 | (2S,3S,4S,5S,6R,9S,11S)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-((2S,3S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-pentenyl)-9-ethyl-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one | C32H63NO4Si2 | 详情 | 详情 | |
| (XXIII) | 35881 | (2R,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-((2S,3S,4S,5S,6R,9S,11S)-4-[[tert-butyl(dimethyl)silyl]oxy]-9-ethyl-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undec-2-yl)-2-methylbutanal | C31H61NO5Si2 | 详情 | 详情 | |
| (XXV) | 35882 | (E,4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-((2S,3S,4S,5S,6R,9S,11S)-4-[[tert-butyl(dimethyl)silyl]oxy]-9-ethyl-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undec-2-yl)-4-methyl-2-hexenal | C33H63NO5Si2 | 详情 | 详情 | |
| (XXVI) | 35883 | (4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-((2S,3S,4S,5S,6R,9S,11S)-4-[[tert-butyl(dimethyl)silyl]oxy]-9-ethyl-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undec-2-yl)-4-methylhexanal | C33H65NO5Si2 | 详情 | 详情 | |
| (XXVII) | 35884 | diethyl 1-diazo-2-oxopropylphosphonate | C7H13N2O4P | 详情 | 详情 | |
| (XXVIII) | 35885 | (2S,3S,4S,5S,6R,9S,11S)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-((2S,3S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-6-heptynyl)-9-ethyl-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one | C34H65NO4Si2 | 详情 | 详情 | |
| (XXIX) | 35886 | (2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-2-[(2S,3S)-2-hydroxy-3-methyl-6-heptynyl]-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one | C22H37NO4 | 详情 | 详情 | |
| (XXX) | 32435 | (2S,3R,4S,5S,6R,9S,11S)-2-[(2S,3S)-7-bromo-2-hydroxy-3-methyl-6-heptynyl]-9-ethyl-4-hydroxy-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one | C22H36BrNO4 | 详情 | 详情 |