Total Synthesis of Spirotenuipesines A and B

Abstract

Spirotenuipesines A and B, isolated from the entomopathogenic fungus <i>Paecilomyces tenuipes</i> by Oshima and co-workers, have been synthesized. The synthesis features the highly stereoselective construction of two vicinal all-carbon quaternary centers (C₅ and C₆) via an intramolecular cyclopropanation/radical initiated fragmentation sequence and a diastereoselective intermolecular Diels−Alder reaction between α-methylenelactone dienophile <b>20</b> and synergistic diene <b>6a</b>. Installation of the C₉ tertiary alcohol occurred via nucleophilic methylation. An RCM reaction to produce a tetrasubstituted double bond in the presence of free allylic alcohol and homoallylic oxygenated functional group is also described. This route shortened the synthesis of <b>11</b> from 9 steps to 3 steps. We have further developed a strategy to gain access to optically active spirotenuipesines A and B through the synthesis of enantioenriched <b>10</b> from commercially available <i>R</i>-(−)-epichlorohydrin