|
【结 构 式】 
|
【分子编号】15731 【品名】(2R)-2-hydroxy-3-(methylsulfanyl)propionic acid 【CA登记号】 |
【 分 子 式 】C4H8O3S 【 分 子 量 】136.17172 【元素组成】C 35.28% H 5.92% O 35.25% S 23.55% |
合成路线1
该中间体在本合成路线中的序号：(IV)D-Serine (I) is nitrosated in the presence of bromide ion to give (R)-2-bromo-3-hydroxypropanoic acid (II), which is converted into (R)-2-hydroxy-3-(methylthio)propanoic acid (IV), via the epoxy acid (III), using sodium methoxide followed by sodium methanethiolate. This hydroxy acid (IV) is coupled to (S)-3-(acetylthio)-2-methylpropanoic acid using either the imidazolide or acid chloride. Final deprotection of 2(R)-[3-(acetylthio)-2(S)-methyl-1-oxopropoxy]-3-(methylthio)propanoic acid (V) is achieved using aqueous ammonia. FPL 66564 is conveniently isolated either as the 1-adamantanamine or L-lysine salt.
| 【1】 Baxter, A.J.G.; Meghani, P. (Celltech Medeva plc); Angiotensin converting enzyme inhibitors. EP 0535496; JP 1993507919; US 5348978; WO 9200276 . |
| 【2】 Fraser-Rae, L.; Eyley, S.C.; Baxter, A.J.G.; Hallam, C.; Harper, S.T.; King, S.J.; Carr, R.D.; Hurved, P.A.; Meghani, P.; (R)-2-(3-Mercapto-2(S)-methyl-1-oxopropoxy)-3-(methylthio)propanoic acid (FPL 66564), the first ultra short-acting angiotensin converting enzyme inhibitor (USACEI). J Med Chem 1992, 35, 3718-20. |
| 【3】 Carr, R.D.; Baxter, A.J.G.; FPL 66564. Drugs Fut 1993, 18, 1, 12. |
| 【4】 Baxter, A.J.G.; Hallam, C.; Harper, S.T.; Meghani, P.; FPL 66564, the first ultra short-acting angiotensin converting enzyme inhibitor (USACEI). J Hypertension 1992, 10, Suppl. 4, S147. |
| 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) | 15728 | (+)-2-Amino-3-hydroxypropionic acid; D-(+)-Serine; D-serine | 312-84-5 | C3H7NO3 | 详情 | 详情 |
| (II) | 15729 | (2R)-2-bromo-3-hydroxypropionic acid | C3H5BrO3 | 详情 | 详情 | |
| (III) | 15730 | Oxirane-2(S)-carboxylic acid sodium salt | C3H3NaO3 | 详情 | 详情 | |
| (IV) | 15731 | (2R)-2-hydroxy-3-(methylsulfanyl)propionic acid | C4H8O3S | 详情 | 详情 | |
| (V) | 15732 | (2R)-2-[[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]oxy]-3-(methylsulfanyl)propionic acid | C10H16O5S2 | 详情 | 详情 |