β2-AR别构拮抗剂Cmpd 15关键中间体(S)-9-芴基甲氧羰基-4-甲酰胺基苯丙氨酸的合成  

Synthesis of(S)-Fmoc-4-carbamoylphenylalanine,The Key Intermediate forβ2-AR Allosteric Inhibitor Cmpd 15

作　　者：赵帅[1] 芮雪 钱明成 陈新[1] ZHAO Shuai;RUI Xue;QIAN Ming-cheng;CHEN Xin(School of Pharmacy, Changzhou University, Changzhou 213164, China)

机构地区：[1]常州大学药学院,江苏常州213164

出　　处：《合成化学》2020年第12期1049-1054,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金青年基金资助项目(21602018)。

摘　　要：报道了β2-AR别构拮抗剂Cmpd 15的关键中间体——(S)-9-芴基甲氧羰基-4-甲酰胺基苯丙氨酸(12)的不对称合成方法。首先,二苯亚胺甘氨酸叔丁酯与对甲酸苄酯苄溴在手性相转移催化剂作用下发生不对称烷基化反应,以94%的产率和98%的ee值制得相应产物;接着经水解、脱保护基和酰胺化等多步反应成功合成了12。通过在其羧酸端引入长链的聚乙二醇羧酸酯结构,成功测得了12的ee值(97%)。产物的结构经1H NMR,13C NMR和HR-MS(ESI)确证。The asymmetric synthesis of(S)-Fmoc-4-carbamoylphenylalanine(12),the key intermediate ofβ2-AR allosteric inhibitor Cmpd 15 was developed.Firstly,asymmetric alkylation of tert-butyl diphenylimine glycine with 4-(bromomethyl)benzamide by chiral phase-transfer catalysts was accomplished.The product was afforded with 94%yield and 98%ee.Secondly,after several transformations,including hydrolysis,deprotection and amidation,compound 12 was successfully obtained.The ee value(97%)of the intermediate was measured by introducing a long-chain polyethylene glycol carboxylate at its carboxylic acid end.The structure of the product was confirmed by 1H NMR,13C NMR and HR-MS(ESI).

关 键 词：β2-AR别构拮抗剂 不对称烷基化 聚乙二醇羧酸酯 相转移催化 苯丙氨酸 

分 类 号：O626[理学—有机化学] R914.5[理学—化学]