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

doi:10.12052/gdutxb.190070

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

更新时间：2026-05-27

- A New Synthetic Route for Small-Molecule Inhibitor of Prostate Specific Membrane Antigen
- Vol. 37, Issue 3, Pages: 95-100(2020)
- 作者机构：
  
  广东工业大学生物医药学院,广东,广州,510006
- 作者简介：
- 基金信息：
- DOI：10.12052/gdutxb.190070
  CLC： O621.3
- Online First：12 May 2020，
  
  Published：2020
- 稿件说明：
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肖清炜, 常媛媛, 刘起发, 臧小豪, 胡蒙蒙, 周渭. 一种前列腺特异性膜抗原小分子抑制剂的合成新路线[J]. 广东工业大学学报, 2020, 37(3): 95-100.

Xiao Qing-wei, Chang Yuan-yuan, Liu Qi-fa, et al. A New Synthetic Route for Small-Molecule Inhibitor of Prostate Specific Membrane Antigen[J]. 2020, 37(3): 95-100.
肖清炜, 常媛媛, 刘起发, 臧小豪, 胡蒙蒙, 周渭. 一种前列腺特异性膜抗原小分子抑制剂的合成新路线[J]. 广东工业大学学报, 2020, 37(3): 95-100. DOI： 10.12052/gdutxb.190070.

Xiao Qing-wei, Chang Yuan-yuan, Liu Qi-fa, et al. A New Synthetic Route for Small-Molecule Inhibitor of Prostate Specific Membrane Antigen[J]. 2020, 37(3): 95-100. DOI： 10.12052/gdutxb.190070.

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

H NMR

C NMR及HR-MS(ESI)表征鉴定。针对中间体N

-(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%。

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

H NMR

C NMR and HR-MS(ESI). A new synthetic method was designed for the synthesis of intermediate tert-butyl N

-(((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%.

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references

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CHEN X C, YANG D Y, CHE X Y at al. Synthesis of PSMA-targeted small molecule Glu-Urea-Lys analogue [J]. Journal of Dalian Medical University, 2012, 34(1): 13-17.

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