消炎镇痛药萘普生不对称合成

ASYMMETRIC SYNTHESIS OF NAPROXEN，AN ANTIINFLAMMATERY ANALGESIC

摘要: 目的：不对称合成非麻醉性消炎镇痛药萘普生［(S)-(+)-2-(6′-甲氧基-2′-萘基)丙酸］。方法：以(2R，3R)-酒石酸二甲酯为手性辅助剂，6-甲氧基-2-丙酰基萘经缩酮化、不对称溴化、水解、重排和催化氢转移氢解等反应合成了光学活性萘普生。结果：化学总收率54%。制备的萘普生的光学纯度(［α］²⁵_D +63.5°)符合中华人民共和国药典(1995年版)的要求。结论：不对称合成萘普生的化学收率和光学收率较高。

Abstract: AIM: To systhesize naproxen by asymmetric method. METHODS: Naproxen was systhesized by acetalization, asymmetric bromination, hydrolysis, rearrangement and catalytic tranfer hydrogenolysis from 6-methoxy-2-propionyl naphthalene, using (2R,3R)-dimethyltartrate as chiral auxiliary, Br₂ as brominating agent, KH₂PO₄ as rearrangement agent, 10% Pd-C/HCO2NH4 as catalytic transfer hydrogenolytic agent. RESULTS: Total yield was 54%, e.e. value of product was 94%. CONCLUSION: The higher chemical yield and optical yield were obtained.