Synthesis of the spiroimine fragment of portimines A and B.

Abstract

Portimines A and B are spirocyclic imine natural products, which display remarkable anticancer, anti-HIV, and antifouling activities. Herein, we report a facile synthesis of the spirocyclic core of portimines A and B. Our strategy utilized a scalable Diels-Alder addition of a 2-bromo-1,3-butadiene to a symmetrical malonate dienophile, coupled with a diastereoselective lactonization of the resulting malonate that enabled differentiation of the two carbonyl groups. This approach overcame issues encountered in previous studies focused on the use of exo selective Diels-Alder reactions, by programming formation of the key stereodiad of the spiroimine fragment into the diastereoselective lactonization event, rather than the cycloaddition step. Elaboration of the key lactone intermediate afforded a functionalized spirolactam fragment as a useful intermediate en route to the portimines. Importantly, a key alcohol intermediate could be resolved by enzymatic resolution, thereby providing an asymmetric route to the spiroimine fragment of portimines A and B.