[Total synthesis of marine cyclic guanidine compounds and development of novel guanidine type asymmetric organocatalysts]

Abstract

Crambescidins and batzelladines, novel marine guanidine alkaloids, have unique pentacyclic and tricyclic guanidine core structures, respectively. They display a considerable array of biological activity and not surprisingly have attracted considerable synthetic interest. The first total synthesis of crambescidin 359 (7) and stereoselective total synthesis of batzelladine D (11) were accomplished based on a successive 1,3-dipolar cycloaddition reaction strategy. During synthetic studies of 7, the absolute stereochemistry was revealed. Based on the structure of 7, the novel C2-symmetric pentacyclic guanidine compounds 69a-d were designed and synthesized as guanidine organocatalysts. The catalyst 69b works efficiently as an asymmetric catalyst of the alkylation reaction of the glycynate-benzophenone Schiff base 73, which gives 74 with 80-90% ee.