一种前列腺特异性膜抗原小分子抑制剂的合成新路线  

A New Synthetic Route for Small-Molecule Inhibitor of Prostate Specific Membrane Antigen

作　　者：肖清炜 常媛媛 刘起发 臧小豪 胡蒙蒙 周渭 Xiao Qing-wei;Chang Yuan-yuan;Liu Qi-fa;Zang Xiao-hao;Hu Meng-meng;Zhou Wei(School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006

出　　处：《广东工业大学学报》2020年第3期95-100,共6页Journal of Guangdong University of Technology

基　　金：国家自然科学基金青年基金资助项目(81502911)。

摘　　要：以L-谷氨酸和L-赖氨酸为原料,经7步反应合成得到了具有谷氨酸-脲(Glu-Urea)骨架的前列腺特异性膜抗原小分子抑制剂,除了L-谷氨酸二叔丁基酯的合成,每一步的产率均高于60%,路线总产率为18%。产物经1H NMR,13C NMR及HR-MS(ESI)表征鉴定。针对中间体N6-(9-芴甲氧羰基)-L-赖氨酸叔丁酯的合成设计了一种合成新思路,一步实现了对赖氨酸α氨基的脱保护与羧基的Boc保护,简化了反应步骤,化合物3的合成产率由约20%提升到70%。Small molecular inhibitor with Glu-Urea skeleton of Prostate Specific Membrane Antigen was synthesized by 7 steps using L-glutamic acid and L-lysine as starting materials.The yield of each step was higher than 60%except for the synthesis of L-di-tert-butyl glutamate.The total yield of the route was 18%.The products were characterized by 1H NMR,13C NMR and HR-MS(ESI).A new synthetic method was designed for the synthesis of intermediate tert-butyl N6-(((9 H-fluoren-9-yl)methoxy)carbonyl)-L-lysinate,which realized the deprotection of lysine alpha amino group and the protection of carboxyl group by Boc in one step,simplified the reaction steps and increased the synthetic yield of compound 3 from 20%to 70%.

关 键 词：L-谷氨酸 L-赖氨酸 前列腺特异性膜抗原 小分子抑制剂 

分 类 号：O621.3[理学—有机化学]