Synthesis of Substituted (+)-Bicuculline Derivatives Through Chloromethylation

Abstract

Treatment of the phthalide isoquinoline alkaloid (+)- bicuculline with paraformaldehyde and hydrochloric acid leads to the chloromethyl derivative (4) which can be further substituted with ammonia or piperazine . In reactions to study methods of linking bicuculline to macromolecules or to photolabile groups, the amino product (7a) has been further functionalized by the formation of amide linkages with succinic anhydride and 4-aminobenzoic acid.