广东工业大学学报 ›› 2020, Vol. 37 ›› Issue (03): 95-100.doi: 10.12052/gdutxb.190070

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一种前列腺特异性膜抗原小分子抑制剂的合成新路线

肖清炜, 常媛媛, 刘起发, 臧小豪, 胡蒙蒙, 周渭   

  1. 广东工业大学 生物医药学院, 广东 广州 510006
  • 收稿日期:2019-05-15 出版日期:2020-05-12 发布日期:2020-05-21
  • 通信作者: 周渭(1987-),男,讲师,博士,主要研究方向为神经炎症相关的药物化学, E-mail:Zhou_wei@gdut.edu.cn E-mail:Zhou_wei@gdut.edu.cn
  • 作者简介:肖清炜(1994-),男,硕士研究生,主要研究方向为药物化学
  • 基金资助:
    国家自然科学基金青年基金资助项目（81502911）

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

Xiao Qing-wei, Chang Yuan-yuan, Liu Qi-fa, Zang Xiao-hao, Hu Meng-meng, Zhou Wei   

  1. School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
  • Received:2019-05-15 Online:2020-05-12 Published:2020-05-21

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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%。

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

Abstract: 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-(((9H-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%.

Key words: L-glutamic acid, L-lysine, prostate specific membrane antigen, small-molecule inhibitors

中图分类号: 

  • O621.3
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