Ubenimex, Ubestatin, NK-421, Bestatin
乌苯美司Chemical Name: (-)-N-[(2S,3R)-3-Amino-2-hydroxy-4-phenylbutyryl]-L-leucine
CAS No. 58970-76-6
项目整合开发状态: Launched-1987
项目研究机构: Nippon Kayaku (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Process for producing threo-3-amino-2-hydroxybutanoyl-aminoacetic acids,as well as novel intermediated therefor and process for producing them
文献作者:Umezawa,H.; Aoyagi,T.; Shirai,T.; Nishizawa,R.; Suzuki,M.; Saino,T.(Nippon Kayaku Co.,Ltd.)
参考来源:DE 2947140; ES 486572; FR 2442227; GB 2090595; US 4281180
📄 详细内容
合成路线: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.
参考文献标题:Bestatin
文献作者:Castar,J.; Blancafort,P.; Serradell,M.N.
参考来源:Drugs Fut 1981,6(10),604
产品链接: CAS No. 58970-76-6››