Total Synthesis of Penicyclone A Using a Double Grignard Reaction

Abstract

We describe the first total synthesis of penicyclone A, a novel deep-sea fungus-derived polyketide, and a reevaluation of its antimicrobial activity. The synthesis of this unique spirolactone was achieved in 10 steps starting from a known D-ribose derivative. The key steps include a double Grignard reaction for the diastereoselective construction of the chiral tertiary alcohol intermediate, tandem oxidation/cyclization, and photooxygenation, followed by an oxidative rearrangement to introduce the enone functionality.