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.