Synthesis of the naphthoquinone core of divergolides (C–D) and model studies for elaboration of the ansabridge

Herein, we describe a facile synthesis of the naphthoquinone fragment of the aromatic core of the novel ansamycins such as hygrocins A–B and the divergolides C–D, starting from the inexpensive 2-hydroxy-3-methylbenzoic acid. We demonstrate the utility of naphthalenic synthon for further elaboration of the ansabridge via C5–C6 bond formation by employing a commercially available sterically demanding organomagnesium reagent as a model ansa chain. Facile conversion of the resulting alcohol to the naphthoquinone fragment of the targets in one pot has also been realized. These model studies set the stage for the completion of total synthesis of the biologically important novel ansamycins.