Unified Route to the Palmarumycin and Preussomerin Natural Products. Enantioselective Synthesis of (−)-Preussomerin G

Abstract

The total syntheses of eight members of the palmarumycin family have been achieved, with identification of the absolute stereochemistry for three of these natural products. In addition, the ras-farnesyl transferase inhibitor (-)-preussomerin G has been synthesized, achieving the first enantioselective route for accessing this family of natural products. Highlights of the synthetic work include an asymmetric epoxidation of a cyclic enone in excellent yield and enantiomeric excess and a potentially biomimetic oxidative spirocyclization for the introduction of the bis-spiroketal array unique to the preussomerin natural products.