FPL-66564

2(R)-[3-巯基-2(S)-甲基丙基桥氧基]-3-(甲硫基)丙酸Chemical Name: 2(R)-[3-Mercapto-2(S)-methylpropanoyloxy]-3-(methylthio)propanoic acid
CAS No. 140369-78-4
项目整合开发状态: Preclinical
项目研究机构: AstraZeneca (Originator)
合成路线: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.
📌 参考资料/链接:
参考文献标题:Angiotensin converting enzyme inhibitors
文献作者:Baxter,A.J.G.; Meghani,P.(Celltech Medeva plc)
参考来源:EP 0535496; JP 1993507919; US 5348978; WO 9200276

📄 详细内容


合成路线: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.

参考文献标题:FPL 66564,the first ultra short-acting angiotensin converting enzyme inhibitor (USACEI)
文献作者:Baxter,A.J.G.; Hallam,C.; Harper,S.T.; Meghani,P.
参考来源:J Hypertension 1992,10(Suppl.4),S147


合成路线: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.

参考文献标题:FPL 66564
文献作者:Carr,R.D.; Baxter,A.J.G.
参考来源:Drugs Fut 1993,18(1),12


合成路线: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.
参考文献标题:(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)
文献作者:Baxter,A.J.G.; Carr,R.D.; Eyley,S.C.; Fraser-Rae,L.; Hallam,C.; Harper,S.T.; Hurved,P.A.; King,S.J.; Meghani,P.
参考来源:J Med Chem 1992,353718-20


产品链接: CAS No. 140369-78-4››