Total Synthesis of Spirotenuipesines A and B

Spirotenuipesines A and B, isolated from the entomopathogenic fungus Paecilomyces tenuipes 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 20 and synergistic diene 6a. 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 11 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 10 from commercially available R-(−)-epichlorohydrin.