Synthesis of pyrrolophenanthridine alkaloids based on C(sp³)[BOND]H and C(sp²)[BOND]H functionalization reactions.

Abstract

Assoanine, pratosine, hippadine, and dehydroanhydrolycorine belong to the pyrrolophenanthridine family of alkaloids, which are isolated from plants of the Amaryllidaceae species. Structurally, these alkaloids are characterized by a tetracyclic skeleton that contains a biaryl moiety and an indole core, and compounds belonging to this class have received considerable interest from researchers in a number of fields because of their biological properties and the challenges associated with their synthesis. Herein, a strategy for the total synthesis of these alkaloids by using C-H activation chemistry is described. The tetracyclic skeleton was constructed in a stepwise manner by C(sp(3))[BOND]H functionalization followed by a Catellani reaction, including C(sp(2))[BOND]H functionalization. A one-pot reaction involving both C(sp(3))[BOND]H and C(sp(2))[BOND]H functionalization was also attempted. This newly developed strategy is suitable for the facile preparation of various analogues because it uses simple starting materials and does not require protecting groups.