Formal Synthesis of (+)-Phomactin A via a Prins/Conia-ene Cascade and -Hydroxylation Strategy

An asymmetric formal synthesis of (+)-phomactin A has been accomplished. The key steps in the synthetic strategy included establishing the AB ring system in one-pot via Prins/Conia-ene cascade cyclization reaction and the C ring formation via gamma-hydroxylation of enone in the late-stage of the synthesis. The two major fragments are readily prepared from (+)-pulegone and geraniol via a modified Eschenmoser-Tanabe fragmentation strategy in 6 steps and a Sharpless asymmetric epoxidation/hydrozirconation/ Roskamp reaction sequence in 11 steps respectively.