Enantioselective total synthesis of atpenin A5

Abstract

Enantioselective total synthesis of atpenin A5, a potent mitochondrial complex II (succinate-ubiquinone oxidoreductase) inhibitor, has been achieved by a convergent approach through a coupling reaction between 5-iodo-2,3,4,6- tetraalkoxypyridine and a side-chain aldehyde. The two key segments were synthesized through ortho-metalation/boronation with (MeO) 3 B/oxidation with mCPBA, ortho-iodination, halogen dance reaction, Sharpless epoxidation and regioselective epoxide-opening reaction. This synthetic study resulted in the revision of the earlier reported 1 H-NMR data of the natural atpenin A5 and the confirmation of the stereochemical assignment. © 2009 Japan Antibiotics Research Association All rights reserved.