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【结 构 式】 
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【分子编号】47181 【品名】(2S,3S,4E,6E,8S,9R,10S)-9-[(4-methoxybenzyl)oxy]-2,4,6,8,10-pentamethyl-3-[(triethylsilyl)oxy]-4,6-icosadienal 【CA登记号】 |
【 分 子 式 】C39H68O4Si 【 分 子 量 】629.05202 【元素组成】C 74.47% H 10.9% O 10.17% Si 4.46% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)The reduction of the ester group of (XIX) with DIBAL in dichloromethane gives the alcohol (XX), which is oxidized with TPAP and NMO in the same solvent, yielding the corresponding aldehyde (XXI). The condensation of (XXI) with phosphorane (XVIII) in refluxing THF affords the diunsaturated ester (XXII), which is reduced with DIBAL as before to provide the alcohol (XXIII). The oxidation of (XXIII) with TPAP and NMO as before gives the aldehyde (XXIV), which is condensed with the silyl enol ether (II) by means of Sn(OTf)2, Bu2Sn(OAc)2 and a chiral catalyst to yield the unsaturated thioester (XXV). The reaction of the OH group of (XXV) with Tes-OTf and lutidine in dichloromethane affords the silyl ether (XXVI), which is reduced with DIBAL in the same solvent to provide the corresponding aldehyde (XXVII).
| 【1】 Wakabayashi, T.; Mori, K.; Kobayashi, S.; Total synthesis and structural elucidation of khafrefungin. J Am Chem Soc 2001, 123, 7, 1372. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 47158 | (Z)-1-(propylsulfanyl)-1-propenyl trimethylsilyl ether; trimethyl[[(Z)-1-(propylsulfanyl)-1-propenyl]oxy]silane | C9H20OSSi | 详情 | 详情 | |
| (XI) | 47175 | (E,4S,5R,6S)-5-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-2-hexadecenal | C27H44O3 | 详情 | 详情 | |
| (XVIII) | 47172 | propyl 2-(triphenylphosphoranylidene)propanoate | C24H25O2P | 详情 | 详情 | |
| (XIX) | 47173 | propyl (E,4S,5R,6S)-5-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-2-hexadecenoate | C30H50O4 | 详情 | 详情 | |
| (XX) | 47174 | (E,4S,5R,6S)-5-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-2-hexadecen-1-ol | C27H46O3 | 详情 | 详情 | |
| (XXII) | 47176 | ethyl (2E,4E,6S,7R,8S)-7-[(4-methoxybenzyl)oxy]-2,4,6,8-tetramethyl-2,4-octadecadienoate | C32H52O4 | 详情 | 详情 | |
| (XXIII) | 47177 | (2E,4E,6S,7R,8S)-7-[(4-methoxybenzyl)oxy]-2,4,6,8-tetramethyl-2,4-octadecadien-1-ol | C30H50O3 | 详情 | 详情 | |
| (XXIV) | 47178 | (2E,4E,6S,7R,8S)-7-[(4-methoxybenzyl)oxy]-2,4,6,8-tetramethyl-2,4-octadecadienal | C30H48O3 | 详情 | 详情 | |
| (XXV) | 47179 | S-propyl (2S,3S,4E,6E,8S,9R,10S)-3-hydroxy-9-[(4-methoxybenzyl)oxy]-2,4,6,8,10-pentamethyl-4,6-icosadienethioate | C36H60O4S | 详情 | 详情 | |
| (XXVI) | 47180 | S-propyl (2S,3S,4E,6E,8S,9R,10S)-9-[(4-methoxybenzyl)oxy]-2,4,6,8,10-pentamethyl-3-[(triethylsilyl)oxy]-4,6-icosadienethioate | C42H74O4SSi | 详情 | 详情 | |
| (XXVII) | 47181 | (2S,3S,4E,6E,8S,9R,10S)-9-[(4-methoxybenzyl)oxy]-2,4,6,8,10-pentamethyl-3-[(triethylsilyl)oxy]-4,6-icosadienal | C39H68O4Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXVII)The condensation of aldehyde (XXVII) with phosphorane (XVIII) in refluxing THF gives the triunsaturated ester (XXVIII), which is reduced with DIBAL in dichloromethane to yield the primary alcohol (XXIX), which is oxidized with TPAP and NMO, affording the aldehyde (XXX). Further oxidation of (XXX) with NaClO2 in tert-butanol/water provides the carboxylic acid (XXXI), which is esterified with the chiral alcohol (XXXII) by means of DCC and DMAP in refluxing dichloromethane to give the ester (XXXIII). Elimination of the silyl protecting groups of (XXXIII) with HCl in THF yields the dihydroxy compound (XXXIV). Oxidation of the secondary and primary OH groups of (XXXIV) with DMP and NaClO2 affords the corresponding oxo acid (XXXV), which is finally treated with BCl3 in dichloromethane to eliminate the Pmb protecting groups and afford the target compound.
| 【1】 Wakabayashi, T.; Mori, K.; Kobayashi, S.; Total synthesis and structural elucidation of khafrefungin. J Am Chem Soc 2001, 123, 7, 1372. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 47172 | propyl 2-(triphenylphosphoranylidene)propanoate | C24H25O2P | 详情 | 详情 | |
| (XXVII) | 47181 | (2S,3S,4E,6E,8S,9R,10S)-9-[(4-methoxybenzyl)oxy]-2,4,6,8,10-pentamethyl-3-[(triethylsilyl)oxy]-4,6-icosadienal | C39H68O4Si | 详情 | 详情 | |
| (XXVIII) | 47182 | ethyl (2E,4R,5S,6E,8E,10S,11R,12S)-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5-[(triethylsilyl)oxy]-2,6,8-docosatrienoate | C44H76O5Si | 详情 | 详情 | |
| (XXIX) | 47183 | (2E,4R,5S,6E,8E,10S,11R,12S)-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5-[(triethylsilyl)oxy]-2,6,8-docosatrien-1-ol | C42H74O4Si | 详情 | 详情 | |
| (XXX) | 47184 | (2E,4R,5S,6E,8E,10S,11R,12S)-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5-[(triethylsilyl)oxy]-2,6,8-docosatrienal | C42H72O4Si | 详情 | 详情 | |
| (XXXI) | 47185 | (2E,4R,5S,6E,8E,10S,11R,12S)-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5-[(triethylsilyl)oxy]-2,6,8-docosatrienoic acid | C42H72O5Si | 详情 | 详情 | |
| (XXXII) | 47186 | (2R,3R,4R)-5-[[tert-butyl(dimethyl)silyl]oxy]-1,3,4-tris[(4-methoxybenzyl)oxy]-2-pentanol | C35H50O8Si | 详情 | 详情 | |
| (XXXIII) | 47187 | (1R,2S,3R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2,3-bis[(4-methoxybenzyl)oxy]-1-[[(4-methoxybenzyl)oxy]methyl]butyl (2E,4R,5S,6E,8E,10S,11R,12S)-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5-[(triethylsilyl)oxy]-2,6,8-docosatrienoate | C77H120O12Si2 | 详情 | 详情 | |
| (XXXIV) | 47188 | (1R,2S,3R)-4-hydroxy-2,3-bis[(4-methoxybenzyl)oxy]-1-[[(4-methoxybenzyl)oxy]methyl]butyl (2E,4R,5S,6E,8E,10S,11R,12S)-5-hydroxy-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-2,6,8-docosatrienoate | C65H92O12 | 详情 | 详情 | |
| (XXXV) | 47189 | (2S,3S,4R)-2,3,5-tris[(4-methoxybenzyl)oxy]-4-([(2E,4R,6E,8E,10S,11R,12S)-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5-oxo-2,6,8-docosatrienoyl]oxy)pentanoic acid | C65H88O13 | 详情 | 详情 |