An approach to canthine derivatives using the intramolecular Pictet-Spengler condensation

Abstract

The canthine derivative 1b was synthesized efficiently by treatment of N a-(4,4-diethoxybutyl)-N b-allyloxytryptamine 9b with TFA/H 2O in chloroform. This result demonstrates that PS cyclization can indeed occur by direct attack of the indole 2-position at the intermediate iminium ion under mild conditions. With N a-propanal chains, only dimeric and oligomeric compounds were isolated. With the N a-pentanal chain (unidentified) oligomeric compounds were formed as well. The monomeric canthine-like products have not been detected in these cases, probably because formation has to proceed via conformationally disfavored intermediate cyclic iminium ions. Cyclization of N a-butanal functionalized N b-formyl- or N b-benzyltryptamines 9c and 9d, which are known rate enhancing substituents in the PS condensation, unexpectedly gave the 3,4-dihydro pyrimidino[1,2- a]indoles 16c,d in high yields. The products 16c,d were formed by a direct electrophilic attack of the protonated aldehydes on the indole 2-position.