SYNTHETIC STUDIES ON DIDYMELINE USING SPIROCYCLIZATION OF PHENOLS WITH DIAZO FUNCTIONALITY

Didymeline is an alkaloid with an azaspiro tricyclic skeleton with various functionalities. Despite the fact that its unique architecture is synthetically attractive, its total synthesis has never been achieved before. Herein, we present synthetic studies on the core structure of didymeline. Accordingly, a spiro ring system was constructed through dearomatization of a phenol derivative with alpha-diazoamide unit. Based on the resulting 2-azaspiro[4,5]decane variant, a tricyclic molecule was synthesized via base-promoted intramolecular ring closure. For an asymmetric synthesis, an enantioselective dearomatization was also examined under silver catalysis, which led to the formation of an all-carbon substituted quaternary stereogenic center.

Automated summary

This study explores the chemical synthesis of the core structure of Didymeline. A tricyclic molecule containing a spiro ring system was successfully synthesized, and enantioselective reactions under silver catalysis were investigated.