(S)-naproxen製程技術發展

　　　　　工業上，(S)-naproxen之製程技術主要可歸納為外消旋物分割法以及對掌性原 （ prochiral ）非對稱合成法。 前者以美國 Syntex 公司開發之非鏡像異構物結晶分割製 程為代表，且目前所生產之 (S)-naproxen 最具競爭力。然而近年來，非對稱合成法之進展 突飛猛進，若能在操作條件、觸媒製備與配位子選擇、降低原料價格及發展為連續式製程上 進一步改善， 則未來將有機會取代現有分割製程之空間。 此外， 發展動態動力分割法（ dynamic kinetic resolution ）以同時進行分割與消旋反應亦是一個可以努力的方向， 例 如以脂肪酵素（ lipases ）及有機鹼為觸媒進行外消旋 naproxen 硫酯動態動力分割， 可 得到產率及光學純度分別大於 97% 及 96% 之 (S)-naproxen 目標產物。
　　　　　(S)-Naproxen can be obtained by employing the resolution from the racemate or the asymmetric synthesis from the prochiral compound. For the former, a representative is the diastereomeric crystallization process developed by Syntex that is now the most competitive in industry. Asymmetric synthesis can compete with the resolution process if more improvements in the operation conditions, catalyst preparation and ligand selection, cost down of the raw material and development into a continuous process are found. Dynamic kinetic resolution represents another solution, as more than 97% conversion and 96% stereo-purity of (S)-naproxen were obtained when lipase and organic amine were the catalysts with racemic naproxen thioester as the substrate.