|
【结 构 式】 
|
【药物名称】Loxistatin, Aloxistatin, E-64-d, EST, Estate 【化学名称】(+)-(2S,3S)-2,3-Epoxy-N-[1(S)-(N-isopentylcarbamoyl)-3-methylbutyl]succinamic acid ethyl ester 【CA登记号】88321-09-9, 96244-68-7 (undefined stereoch.) 【 分 子 式 】C17H30N2O5 【 分 子 量 】342.43905 |
【开发单位】Taisho (Originator), Sumitomo Pharmaceuticals (Licensee) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Cysteine Protease Inhibitors |
合成路线1
The estrification of L-trans-epoxysuccinic acid hemi-ethyl ester (I) with 4-nitrophenol (II) by means of dicyclohexylcarbodiimide (DCC) gives the corresponding p-nitrophenyl ester (III), which is then condensed with N-isoamyl L-leucinamide (IV).
| 【1】 Soda, K.; et al. (Taisho Pharmaceutical Co., Ltd.); Trans-epoxysuccinic acid derivative. JP 60174777 . |
| 【2】 Castaner, J.; Prous, J.; EST. Drugs Fut 1986, 11, 11, 927. |
| 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) | 24344 | (2S,3S)-3-(ethoxycarbonyl)-2-oxiranecarboxylic acid | C6H8O5 | 详情 | 详情 | |
| (II) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
| (III) | 24346 | 2-ethyl 3-(4-nitrophenyl) (2S,3S)-2,3-oxiranedicarboxylate | C12H11NO7 | 详情 | 详情 | |
| (IV) | 24347 | 2-amino-N-isopentyl-4-methylpentanamide | C11H24N2O | 详情 | 详情 |
合成路线2
The synthesis of [14 C]-EST has been described ac cording to the following procedure: The oxidation of fumaric acid (I) with H2O2 gives trans-epoxysuccinic acid (II), which is submitted to optical resolution by means of its salt with L-arginine. The L-trans isomer (III) is esterified with ethanol and H2SO4 to the corresponding diethyl ester (IV), which is hydrolyzed selectively with KOH, affording the monoethyl ester (V). Finally, this monoester 5 condensed with N-isoamyl-L-leucinamide (VI).
| 【1】 Fukushima, K.; et al.; In vivo actions of EST (reort 1) - Absorption and excretion of 14C-EST. Kiso To Rinsho 1986, 20, 4, 319. |
| 【2】 Castaner, J.; Prous, J.; EST. Drugs Fut 1986, 11, 11, 927. |
| 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) | 23808 | Fumaric acid; (E)-2-butenedioic acid | 110-17-8 | C4H4O4 | 详情 | 详情 |
| (II) | 24349 | 2,3-oxiranedicarboxylic acid; Oxirane-2,3-dicarboxylic acid; Epoxysuccinic acid | C4H4O5 | 详情 | 详情 | |
| (III) | 24350 | (2S,3S)-2,3-oxiranedicarboxylic acid | C4H4O5 | 详情 | 详情 | |
| (IV) | 24351 | diethyl (2S,3S)-2,3-oxiranedicarboxylate | 74243-85-9 | C8H12O5 | 详情 | 详情 |
| (V) | 24344 | (2S,3S)-3-(ethoxycarbonyl)-2-oxiranecarboxylic acid | C6H8O5 | 详情 | 详情 | |
| (VI) | 24347 | 2-amino-N-isopentyl-4-methylpentanamide | C11H24N2O | 详情 | 详情 |