Enantioselective Total Syntheses of Citrinadins A and B. Stereochemical Revision of Their Assigned Structures

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.