Total Synthesis of (+/-)-Atpenin B. An Original "Clockwise" Functionalization of 2-Chloropyridine

Article abstract of DOI:10.1021/jo00100a017

(-)-Atpenin B (1) is an antibiotic produced by Penicillim sp.FO-125.The first synthesis of 2,4-dihydroxy-5,6-dimethoxy-3-((2RS,4RS)-2,4-dimethyl-1-oxohexyl)pyridine (atpenin B) (16) is reported.This molecule, which exhibits a pentasubstituted pyridine structure, was prepared from 2-chloropyridine in 13 steps, by metalating and then functionalizing, one after another, all the remaining positions of the pyridine ring.The methodology involves four metalation steps (including metalation of 2,3-dimethoxypyridine and pyridyl N,N-diisopropylcarbamates), one halogen-scrambling step, and one bromine-lithium exchange step.