Improved Process for Pilot-Scale Synthesis of Danshensu ((卤)-DSS) and Its Enantiomer Derivatives

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• 作者：Yajun Bai ; Qunzheng Zhang ; Pu Jia ; Lingjian Yang ; Yuhong Sun ; Yefei Nan ; Shixiang Wang ; Xue Meng ; Yizhen Wu ; Fanggang Qin ; Zhe Sun ; Xiaokang Gao ; Pei Liu ; Kai Luo ; Yajun Zhang ; Xinfeng Zhao ; Chaoni Xiao ; Sha Liao ; Jianli Liu ; Cuiling Wang ; Jiacheng Fang ; Xiaoxiao Wang ; Jing Wang ; Rong Gao ; Xuexia An ; Xunli Zhang ; Xiaohui Zheng
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：December 19, 2014
• 年：2014
• 卷：18
• 期：12
• 页码：1667-1673
• 全文大小：276K
• ISSN：1520-586X

文摘

A pilot-scale process has been developed for green and scalable synthesis of (卤)-尾-(3,4-dihydroxyphenyl) lactic acid ((卤)-DSS) and their two important derivatives, namely, (卤)-IDHP [(卤)-isopropyl 2-hydroxy-3-(3,4-dihydroxyphenyl)propanoate] and (卤)-DBZ [(卤)-bornyl 2-hydroxy-3-(3,4-dihydroxyphenyl)propanoate]. Subsequent hydrogenation has been carried out by employing Raney Ni as catalyst. The improved process results in higher yields of 47.5% for (卤)-DBZ and 49.2% for (卤)-IDHP compared to the initial process with a yield of 12% for (卤)-DBZ and 18% for (卤)-IDHP in our original medicinal chemistry route. Furthermore, kilograms of optical DBZ [(鈭?-S-DBZ and (+)-R-DBZ, >99% ee] and IDHP [(鈭?-S-IDHP and (+)-R-IDHP, >99% ee] have been produced by chiral high-performance liquid chromatography in good yield (>84%).