Bioinspired Chemical Transformations of Grayanotoxin III to Kalmanol, seco-Rhodomollone, and Rhodomolleins XXIII and XXIV.

Grayanotoxin III (GTX III), isolated from Leucothoe grayana Max., was chemically converted into kalmanol, seco-rhodomollone, rhodomollein XXIV, and rhodomollein XXIII in accordance with their proposed biosynthetic hypotheses. The key skeletal rearrangement from the grayanane to the kalmane framework was achieved at low temperature by introducing triflate as the leaving group of the C14 hydroxyl group. Subsequent regio- and stereoselective hydration and global deprotection gave kalmanol in a total of six steps from GTX III. Further conversion to seco-rhodomollone, rhodomollein XXIV, and XXIII demonstrated the putative biosynthetic pathway of these natural products. The present findings establish the route to structurally complex and rare kalmane diterpenoids, which can serve as potential lead compounds for drug discovery and advance the overall understanding of the biogenetic pathway of grayanoids.