非甾体消炎药萘普生不对称合成研究

Asymmetric Synthesis of Naproxen

萘普生[(S)-(+)-2-(6 ＇-甲氧基一2 ＇-萘基)丙酸]是一种非常重要的非甾体消炎镇痛药.以(2R,3R)-酒石酸二甲酯为手性辅助剂,2-甲氧基萘经溴代、丙酰化、缩酮化、不对称溴化、水解、立体专一性重排和催化氢转移氢解等反应合成了光学活性萘普生,化学收率44%.制备的萘普生的光学纯度([α]_D^(25)=+63.5°)符合中华人民共和国药典(1995年版)的要求.

Naproxen was synthesized from 2 - methoxynaphthalene, using (2R,3R) - dimethyl tartrate as chiral auxiliary, DBDMH and Br2 as brominating agent, KH2PO4 as rearrangement agent, 10% Pd - C/ HCO2NH4 as catalytic transfer hydrogenolytic agent via propionylization, asymmetric bromination, hydrolysis, rearrangement and catalytic tranfer hydrogenolysis. Totalyield was 44% (based on 2 - methoxynaphthalene) with the e. e. value of product being 94 % .