14-Step Synthesis of (+)-Ingenol from (+)-3-Carene

Abstract

Ingenol Ingenuity The diterpenoid i ngenol is the core structure of a topical drug recently commercialized to treat actinic keratosis, a precancerous skin condition. Sourcing the compound from the Euphorbia plants that produce it is relatively inefficient, so Jørgensen et al. (p. 878 , published online 1 August) devised a chemical synthesis starting from the comparatively simple and inexpensive monoterpene chiral (+)-3-carene. The synthetic sequence involves 14 steps—less than half as long as prior chemical routes to the target—and relies on a two-stage approach, inspired by the posited biosynthetic pathway, in which preliminary assembly of the fused ring framework precedes hydroxylation of the periphery.