Synthesis of Praziquantel via N-Acyliminium Ion Cyclization of Amido Acetals through Several Synthetic Routes

Syntheses of praziquantel have been accomplished viaan N-acylinium ion by several routes including the tandem nucleophilic addition-cyclization sequence from amido acetal ( 8) or ( 10) and a stepwise cyclization of enamide (9) generated from the nucleophilic addition reaction of amido acetal( 8) or ( 10).The discovery of pradquantel(1) represented as a synthetic drug of pyrazinoisoquinoline derivatives has played an important role in the treatment of cestodiasis disease.' Accordingly, many research groups have extensively investigated on structure-activity relationships of this class of compounds2 and attempted to develop a more efficient synthetic route to praziquantel and its derivative^.^-^Most of the known synthetic methods involve successive constructions of piperazine ring and isoquinoline ring in pyrazinoisoquinoline ring system, which require multistep sequence or vigorous reaction condition^."^On the other hand, we have recently reported an efficient synthesis of praziquantel by a tandem nucleophilic addition followed by N-acyliminium ion cyclization of amido acetal (2) (Scheme Scheme 1