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【结 构 式】 
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【分子编号】47186 【品名】(2R,3R,4R)-5-[[tert-butyl(dimethyl)silyl]oxy]-1,3,4-tris[(4-methoxybenzyl)oxy]-2-pentanol 【CA登记号】 |
【 分 子 式 】C35H50O8Si 【 分 子 量 】626.8627 【元素组成】C 67.06% H 8.04% O 20.42% Si 4.48% |
合成路线1
该中间体在本合成路线中的序号：(XXXII)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 |
合成路线2
该中间体在本合成路线中的序号：(XX)Synthesis of the target compound: The condensation of the iodinated pivalate (X) with the alkenylboronic acid (XV) by means of TlOEt and Pd(PPh3)4 in hot THF gives the adduct (XVI), which is treated with DIBAL in dichloromethane to eliminate the pivaloyl group and yield the primary alcohol (XVII). The oxidation of (XVII) with MnO2 affords the aldehyde (XVIII), which is oxidized to the carboxylic acid (XIX) by means of NaClO2 in tert-butanol/water. The esterification of acid (XIX) with alcohol (XX) by means of DCC and DMAP in refluxing dichloromethane affords the ester (XXI), which is desilylated by means of HCl in THF to provide the dihydroxy compound (XXII). The oxidation of diol (XXII) first with DMP and then with NaClO2 leads to the ketoacid (XXIII), which is finally debenzylated by a treatment with BCl3 in dichloromethane to give the target Khafrefungin.
| 【1】 Kobayashi, S.; Mori, K.; Wakabayashi, T.; Yasuda, S.; Hanada, K.; Convergent total synthesis of khafrefungin and its inhibitory activity of fungal sphigolipid syntheses. J Org Chem 2001, 66, 16, 5580. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 60343 | 1,3,5-trimethyl-4-({[4-(methyloxy)phenyl]methyl}oxy)-1-pentadecenylboronic acid | C26H45BO4 | 详情 | 详情 | |
| (XVI) | 60344 | 7-iodo-2,4,6-trimethyl-5-[(triphenylsilyl)oxy]-2,6-heptadienyl 2,2-dimethylpropanoate | C33H39IO3Si | 详情 | 详情 | |
| (XVII) | 60345 | 2,4,6,8,10,12-hexamethyl-11-({[4-(methyloxy)phenyl]methyl}oxy)-5-[(triphenylsilyl)oxy]-2,6,8-docosatrienyl 2,2-dimethylpropanoate | C59H82O5Si | 详情 | 详情 | |
| (XVIII) | 60347 | 2,4,6,8,10,12-hexamethyl-11-({[4-(methyloxy)phenyl]methyl}oxy)-5-[(triphenylsilyl)oxy]-2,6,8-docosatrienal | C54H72O4Si | 详情 | 详情 | |
| (XIX) | 60348 | 2,4,6,8,10,12-hexamethyl-11-({[4-(methyloxy)phenyl]methyl}oxy)-5-[(triphenylsilyl)oxy]-2,6,8-docosatrienoic acid | C54H72O5Si | 详情 | 详情 | |
| (XX) | 47186 | (2R,3R,4R)-5-[[tert-butyl(dimethyl)silyl]oxy]-1,3,4-tris[(4-methoxybenzyl)oxy]-2-pentanol | C35H50O8Si | 详情 | 详情 | |
| (XXI) | 60350 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,3-bis({[4-(methyloxy)phenyl]methyl}oxy)-1-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]butyl 2,4,6,8,10,12-hexamethyl-11-({[4-(methyloxy)phenyl]methyl}oxy)-5-[(triphenylsilyl)oxy]-2,6,8-docosatrienoate | C89H120O12Si2 | 详情 | 详情 | |
| (XXII) | 60349 | 4-hydroxy-2,3-bis({[4-(methyloxy)phenyl]methyl}oxy)-1-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]butyl 5-hydroxy-2,4,6,8,10,12-hexamethyl-11-({[4-(methyloxy)phenyl]methyl}oxy)-2,6,8-docosatrienoate | C65H92O12 | 详情 | 详情 | |
| (XXIII) | 60347 | 2,4,6,8,10,12-hexamethyl-11-({[4-(methyloxy)phenyl]methyl}oxy)-5-[(triphenylsilyl)oxy]-2,6,8-docosatrienal | C54H72O4Si | 详情 | 详情 |