Wanted: new multicomponent reactions for generating libraries of polycyclic natural products

The amalgamation of two of combinatorial chemistry's most attractive concepts--natural product libraries and multicomponent reactions (MCRs)--should provide a powerful tactic for generating libraries of bioactive compounds, but only a few MCRs can deliver functionalized products whose structures closely resemble that of complex polycyclic natural products.

Abstract

The amalgamation of two of combinatorial chemistry's most attractive concepts--natural product libraries and multicomponent reactions (MCRs)--should provide a powerful tactic for generating libraries of bioactive compounds. Yet, despite many recent advances in this area, only a few MCRs can deliver functionalized products whose structures closely resemble that of complex polycyclic natural products. A large proportion of recently developed MCRs are based on [4+2] or [3+2] cycloadditions, and isocyanide-based processes. Because of substrate limitations, however, they are not always ideally suitable for applications in diversity-oriented synthesis of natural product-like compounds. A promising area awaiting further development is the use of transition metal-catalyzed cascade reactions.