Two approaches for the synthesis of levo praziquantel.
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.
Organic biomolecular chemistry