A Concise Bioinspired Semisynthesis of Rumphellaones A–C and Their C-8 Epimers from β-Caryophyllene

Abstract

The first semisynthetic route toward rumphellaones B (<b>2</b>) and C (<b>3</b>) and their C-8 epimers as well as the shortest synthesis of rumphellaone A (<b>1</b>) and its C-8 epimer from the most accessible sesquiterpene, β-caryophyllene (<b>4</b>), is presented. Synthetic routes involved caryophyllonic acid as a key intermediate, which was converted to rumphellaone A (and epimer) via acid-catalyzed lactonization and rumphellaone C (and epimer) using one-pot epoxidation-lactonization. Rumphellaone B (<b>2</b>) and its epimer were obtained from rumphellaone A (<b>1</b>) and its epimer, respectively, using Saegusa-Ito oxidation. The absolute configuration at C-8 was confirmed by single-crystal X-ray analysis of rumphellaone B (<b>2</b>) and an acylated derivative of rumphellaone C.