Second-Generation Synthesis of (-)-Viriditoxin

Charles I. Grove, James C. Fettinger & Jared T. Shaw
Viriditoxin is a secondary metabolite isolated from Aspergillus­ viridinutans that has been shown to inhibit FtsZ, the bacterial homologue of eukaryotic tubulin. A streamlined, scalable, and highly diastereoselective synthesis of this complex natural product is described. Key advances include a more efficient synthesis of the requisite unsaturated pyranone, scalable assembly of the naphthopyranone monomer, and improved diastereoselectivity in the biaryl-coupling reaction. In addition, we disclose a serendipitous ruthenium-catalyzed anion dimerization resulting from trace metal left...