Total Synthesis of (+)-Raputindole A: An Iridium-Catalyzed Cyclization Approach

Abstract

This work describes the total synthesis of raputindole A ( 1 ) through a convergent approach that features (1) an iridium-catalyzed cyclization to assemble the tricyclic core of the northern part, (2) enzymatic resolution to secure the preparation of an enantiomerically pure benzylic alcohol intermediate, and (3) the installation of the isobutenyl side chain via methallylation of the corresponding benzylic carbocation and coupling of the northern and southern parts via the Heck reaction. (+)-Raputindole A ( 1 ) was prepared in 10 steps (longest linear sequence) in 3.3% overall yield.

Chemo-enzymatic synthesis of natural products and their analogs

“…By enabling transformations in a fashion orthogonal to established chemical approaches, enzymes streamline the preparation of complex natural products and introduce new retrosynthetic disconnections and synthetic strategies. While dearomatization with Rieske dioxygenases 3 and lipase-catalyzed deracemization of early alcohol intermediates [4][5][6][7][8][9] have found a solid foothold in contemporary natural product synthesis, several other classes of enzymes have recently made an appearance in routes toward natural products and their analogues. Owing to their versatility, enzymes have found applications in nearly all phases of (total) synthesis and continue to reshape the way organic chemists approach complex target compounds.…”