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

The first semisynthetic route toward rumphellaones B (2) and C (3) and their C-8 epimers as well as the shortest synthesis of rumphellaone A (1) and its C-8 epimer from the most accessible sesquiterpene, β-caryophyllene (4), 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 (2) and its epimer were obtained from rumphellaone A (1) 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 (2) and an acylated derivative of rumphellaone C.