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.