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【结 构 式】 
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【分子编号】27320 【品名】(8S)-7-[(2S)-2-aminopropanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid 【CA登记号】 |
【 分 子 式 】C10H16N2O3S2 【 分 子 量 】276.38072 【元素组成】C 43.46% H 5.84% N 10.14% O 17.37% S 23.2% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The cyclization of 1-benzyloxycarbonyl-4-oxoproline methyl ester (I) with ethanedithiol (II) by means of p-toluenesulfonic acid in refluxing acetic acid gives methyl 7-benzyloxycarbonyl-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate (III), which is deprotected with 20% HBr to give methyl 1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate (IV). The condensation of (IV) with N-benzyloxycarbonyl alanine N-hydroxysuccinimide ester (V) affords the corresponding dipeptide methyl ester (VI), which is hydrolyzed with NaOH to the free acid (VII), and deprotected with 20% HBr as before to 7-alanyl-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid (VIII). Finally, this compound is condensed with ethyl 2-oxo-4-phenylbutyrate (IX) by means of sodium cyanoborohydride in methanol.
| 【1】 Smith, E.M.; Neustadt, B.R.; Gold, E.H. (Schering Corp.); 7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids. JP 1989163197; US 4470972 . |
| 【2】 Prous, J.; Castaner, J.; Spirapril. Drugs Fut 1987, 12, 9, 860. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 27314 | benzyl hydrogen sulfate | C7H8O4S | 详情 | 详情 | |
| (I) | 27312 | 1-benzyl 2-methyl (2R)-4-oxo-1,2-cyclopentanedicarboxylate | C15H16O5 | 详情 | 详情 | |
| (II) | 27313 | 1,2-ethanedithiol | 540-63-6 | C2H6S2 | 详情 | 详情 |
| (III) | 27315 | 7-benzyl 8-methyl (8R)-1,4-dithiaspiro[4.4]nonane-7,8-dicarboxylate | C17H20O4S2 | 详情 | 详情 | |
| (IV) | 27316 | methyl (8S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate | C8H13NO2S2 | 详情 | 详情 | |
| (V) | 27317 | benzyl (1S)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-methyl-2-oxoethylcarbamate | C15H16N2O6 | 详情 | 详情 | |
| (VI) | 27318 | methyl (8S)-7-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate | C19H24N2O5S2 | 详情 | 详情 | |
| (VII) | 27319 | (8S)-7-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid | C18H22N2O5S2 | 详情 | 详情 | |
| (VIII) | 27320 | (8S)-7-[(2S)-2-aminopropanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid | C10H16N2O3S2 | 详情 | 详情 | |
| (IX) | 20896 | Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester | 64920-29-2 | C12H14O3 | 详情 | 详情 |