TOTAL SYNTHESIS OF (+ -)-ATPENIN-B - AN ORIGINAL CLOCKWISE FUNCTIONALIZATION OF ALPHA-CHLOROPYRIDINE/

(-)-Atpenin B (1) is an antibiotic produced by Penicillium sp. FO-125. The first synthesis of hoxy-3-((2RS,4RS)-2;4-dimethyl-1-oxohexyl)pyri dine (atpenin B) (16) is reported. This molecule, which exhibits a pen tasubstituted pyridine structure, was prepared from 2-chloropyridine i n 13 steps, by metalating and then functionalizing, one after another, all the remaining positions of the pyridine ring. The methodology inv olves four metalation steps (including metalation of 2,3-dimethoxypyri dine and pyridyl N,N-diisopropylcarbamates), one halogen-scrambling st ep, and one bromine-lithium exchange step.