Bioinspired Total Synthesis of (+)-Euphorikanin A

Abstract

We have achieved a bioinspired total synthesis of (+)-euphorikanin A, which possesses an intriguing and complex 5/6/7/3-fused tetracyclic skeleton bearing a bridged [3.2.1]-γ-lactone moiety. Key transformations include stereoselective alkylation and aldol condensation to install the main stereocenters, an intramolecular nucleophile-catalyzed aldol lactonization of carboxylic acid-ketone to assemble the five-membered ring, a McMurry coupling to construct the seven-membered ring, and a biomimetic benzilic acid type rearrangement to form the bridged [3.2.1]-γ-lactone moiety.

Keywords: Asymmetric Synthesis; Bioinspired Synthesis; Natural Products; Terpenoids; Total Synthesis.