Total Synthesis of a Marine Alkaloid—Rigidin E

Abstract

In the present paper, we report an efficient total synthesis of a marine alkaloid, rigidin E. The key tetrasubstituted 2-amino-3-carboxamidepyrrole intermediate was synthesized by cascade Michael addition/intramolecular cyclization between <em>N</em>-(2-(4-(benzyloxy)phenyl)-2-oxoethyl)methanesulfonamide and 3-(4-(benzyloxy)phenyl)-2-cyano-<em>N</em>-methylacrylamide. Subsequent carbonylation with triphosgene catalyzed by I₂ and deprotection of benzyl groups afforded rigidin E in 21% overall yield. This strategy has the merits of metal-free reactions, low cost, mild reaction protocols, and easy access to diversity-oriented derivatives for potential structure-activity relationship investigation.

Keywords

• pyrrolo[2,3-&lt;em&gt;d&lt;/em&gt;]pyrimidine
• alkaloids
• total synthesis
• domino reaction
• marine natural products