Enantioselective total syntheses of citrinadins A and B. Stereochemical revision of their assigned structures.

Abstract

The concise, enantioselective total syntheses of (−)-citrinadin A and (+)-citrinadin B in a total of only 20 and 21 steps, respectively, from commercially available starting materials are described. Our strategy, which minimizes refunctionalization and protection/deprotection operations, features the highly diastereoselective, vinylogous Mannich addition of a dienolate to a chiral pyridinium salt to set the first chiral center. The absolute stereochemistry of this key center was then relayed by a sequence of substrate-controlled reactions, including a highly stereoselective epoxidation/ring opening sequence and an oxidative rearrangement of an indole to furnish a spirooxindole to establish the remaining stereocenters in the pentacyclic core of the citrinadins. An early stage intermediate in the synthesis of (−)-citrinadin A was deoxygenated to generate a dehydroxy compound that was elaborated into (+)-citrinadin B by a sequence of reaction identical to those used to prepare (−)-citrinadin A. These concise syntheses of (−)-citrinadin A and (+)-citrinadin B led to a revision of their stereochemical structures.