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【结 构 式】 
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【药物名称】 【化学名称】N1-[3-(N-Benzyloxysulfamoyl)-1(S)-(2-phenylethyl)-2-propenyl]-N2-(morpholin-4-ylcarbonyl)-L-phenylalaninamide 【CA登记号】 【 分 子 式 】C32H38N4O6S 【 分 子 量 】606.74686 |
【开发单位】University of California, San Francisco (Originator), University of Michigan (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antitrypanosomals, Treatment of Protozoal Diseases, Cysteine Protease Inhibitors |
合成路线1
The Horner-Wadsworth-Emmons olefination of N-(tert-butoxycarbonyl)-L-homophenylalaninal (I) with phosphonate (II) by means of NaH in THF gives the vinylsulfonate (III), which is treated with tetrabutylammonium iodide and triphosgene to yield the sulfonyl chloride (IV). The reaction of (IV) with O-benzylhydroxylamine in dichloromethane affords the N-sulfonylhydroxylamine derivative (V), which is deprotected with TFA in dichloromethane, providing compound (VI) with a free amino group. Finally, this compound is condensed with N-(morpholin-4-ylcarbonyl)-L-phenylalanine (VII) by means of HOBt, EDC and NMM in DMF, giving rise to the target amide.
| 【1】 Roush, W.R.; et al.; Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg Med Chem Lett 2001, 11, 20, 2759. |
| 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) | 23624 | diethyl (phenylsulfonyl)methylphosphonate | C11H17O5PS | 详情 | 详情 | |
| (II) | 51650 | ethyl dimethoxy(oxo)phosphoranesulfonate | C4H11O6PS | 详情 | 详情 | |
| (III) | 51651 | ethyl (E,3S)-3-[(tert-butoxycarbonyl)amino]-5-phenyl-1-pentene-1-sulfonate | C18H27NO5S | 详情 | 详情 | |
| (IV) | 51652 | tert-butyl (1S,2E)-3-(chlorosulfonyl)-1-phenethyl-2-propenylcarbamate | C16H22ClNO4S | 详情 | 详情 | |
| (V) | 51653 | tert-butyl (1S,2E)-3-[[(benzyloxy)amino]sulfonyl]-1-phenethyl-2-propenylcarbamate | C23H30N2O5S | 详情 | 详情 | |
| (VI) | 51654 | (E,3S)-3-amino-N-(benzyloxy)-5-phenyl-1-pentene-1-sulfonamide | C18H22N2O3S | 详情 | 详情 | |
| (VII) | 23627 | (2S)-2-[(4-morpholinylcarbonyl)amino]-3-phenylpropionic acid | C14H18N2O4 | 详情 | 详情 |