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【结 构 式】 
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【分子编号】32263 【品名】(2S,3S)-3-(acetamido)-2-hydroxy-4-oxo-4-phenylbutyric acid; threo-(2RS)-3-acetamido-2-hydroxy-4-oxo-4-phenylbutyric acid 【CA登记号】 |
【 分 子 式 】C12H13NO5 【 分 子 量 】251.23896 【元素组成】C 57.37% H 5.22% N 5.58% O 31.84% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of N-(2-oxo-2-phenylethyl)acetamide (I) with glyoxylic acid (II) by means of NaHCO3 in water gives threo-(2RS)-3-acetylamino-2-hydroxy-4-oxo-4-phenylbutanoic acid (III), which is reduced with H2 over Pd/C in acetic acid yielding threo-(2RS)-3-acetylamino-2-hydroxy-4-phenylbutanoic acid (IV). The treatment of (IV) with (S)-1-phenylethylamine followed by a fractionated crystallization affords (2S,3R)-3-acetyl-amino-2-hydroxy-4-phenylbutanoic acid (IV), which is hydrolyzed with HCl in refluxing water to afford (2R,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid (V). The protection of (V) with benzyl S-4,6-dimethylpyrimidin-2-ylthiolcarbonate (VI) by means of triethylamine in dioxane - water gives (2S,3R)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoic acid (VII), which is condensed whh benzyl (S)-leucinate (VIII) by means of di-cyclohexylcarbodiimide and p-toluenesulfonic acid yielding benzyl (2S,3R)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoyl-(S)-leucinate (IX). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C in acetic acid.
| 【1】 Umezawa, H.; Aoyagi, T.; Shirai, T.; Nishizawa, R.; Suzuki, M.; Saino, T. (Nippon Kayaku Co., Ltd.); Process for producing threo-3-amino-2-hydroxybutanoyl-aminoacetic acids, as well as novel intermediated therefor and process for producing them. DE 2947140; ES 486572; FR 2442227; GB 2090595; US 4281180 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Bestatin. Drugs Fut 1981, 6, 10, 604. |
| 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) | 14601 | N-(2-oxo-2-phenylethyl)acetamide | C10H11NO2 | 详情 | 详情 | |
| (II) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (III) | 32263 | (2S,3S)-3-(acetamido)-2-hydroxy-4-oxo-4-phenylbutyric acid; threo-(2RS)-3-acetamido-2-hydroxy-4-oxo-4-phenylbutyric acid | C12H13NO5 | 详情 | 详情 | |
| (IV) | 32264 | (2S,3R)-3-(acetamido)-2-hydroxy-4-phenylbutyric acid; threo-(2RS)-3-acetamido-2-hydroxy-4-phenylbutyric acid | C12H15NO4 | 详情 | 详情 | |
| (V) | 32265 | (2S,3R)-3-amino-2-hydroxy-4-phenylbutyric acid; (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid | 62023-63-6 | C10H13NO3 | 详情 | 详情 |
| (VI) | 32266 | O-benzyl S-(4,6-dimethyl-2-pyrimidinyl) carbonothioate; benzyl S-4,6-dimethylpyrimidin-2-ylthiolcarbonate | C14H14N2O2S | 详情 | 详情 | |
| (VII) | 32267 | (2S,3R)-3-benzyIoxycarbonyIamino-2-hydroxy-4-phenylbutyric acid; (2S,3R)-3-[[(benzyloxy)carbonyl]amino]-2-hydroxy-4-phenylbutyric acid | C18H19NO5 | 详情 | 详情 | |
| (VIII) | 22252 | Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate | C13H19NO2 | 详情 | 详情 | |
| (IX) | 32268 | benzyl (2S)-2-[((2S,3R)-3-[[(benzyloxy)carbonyl]amino]-2-hydroxy-4-phenylbutanoyl)amino]-4-methylpentanoate; benzyl (2S,3R)-3-Benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoyI-(S)-Ieucinate | C31H36N2O6 | 详情 | 详情 |