Enantioselective total synthesis of atpenin A5

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 H-1-NMR data of the natural atpenin A5 and the confirmation of the stereochemical assignment. The Journal of Antibiotics (2009) 62, 289-294; doi:10.1038/ja.2009.29; published online 17 April 2009