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Two approaches for the synthesis of levo-praziquantel
Haowen Shou1, Zhaoting He2, Gang Peng3
1National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, PR China. yjb@zjut.edu.cn.
Abstract:
We report herein the development of two pathways for the preparation of levo-praziquantel (R-PZQ), which involves three-/four-step processes of a mechanochemical (asymmetric) aza-Henry/acylation reaction, a hydrogenation reaction, (chiral resolution) and a solvent-free acylation-ring closing reaction. The key intermediate (R)-1-aminomethyl tetrahydroisoquinoline could be obtained either by chiral resolution with a rational reuse of the S-isomer or by mechanochemical enantioselective synthesis that refrained from using a bulky toxic solvent. The efficiency and scalability of both the developed routes were demonstrated and desired target product was obtained in a satisfactory yield with excellent enantiopurity (>99%), offering practical, concise and environmentally friendly alternatives to access R-PZQ.
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