A Synthesis of Exiguaquinol Dessulfate.

A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels-Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N-acyl hemiaminal, which was based upon an analysis of internal hydrogen-bonding interactions with polar functional groups, was proven correct. A late-stage intermediate did not demonstrate bactericidal activity against H. pylori cultures.