| Abstract
| - A novel and efficient synthesis of the pyrido[3‘,2‘:4,5]pyrrolo[1,2-c]pyrimidine system, the heterocycliccore of the variolin family of marine alkaloids, is described. The route involves the reaction of3-bromo-2-(bromomethyl)pyrrolo[2,3-b]pyridine and tosylmethyl isocyanide (TosMIC) under phase-transfer conditions. This unprecedented reaction was also used to synthesize a series of newmethoxycarbonyl azolopyrimidines by reaction of TosMIC with bromomethylindoles, bromomethylbenzimidazole, and bromomethylpyrazole. Hydrolysis and decarboxylation of 5-bromo-7-methoxycarbonylpyrido[3‘,2‘:4,5]pyrrolo[1,2-c]pyrimidine obtained by this heterocyclization process andinstallation of the pyrimidine moiety in the C5 position open an alternative approach to completea total synthesis of variolin B.
|
