14-step synthesis of (+)-ingenol from (+)-3-carene.

摘要: Ingenol is a diterpenoid with unique architecture and has derivatives possessing important anticancer activity, including the recently Food Drug Administration–approved Picato, first-in-class drug for treatment of precancerous skin condition actinic keratosis. Currently, that compound sourced inefficiently from Euphorbia peplus. Here, we detail an efficient, highly stereocontrolled synthesis (+)-ingenol proceeding in only 14 steps inexpensive (+)-3-carene using two-phase design. This will allow creation fully synthetic analogs bioactive ingenanes to address pharmacological limitations provides strategic blueprint chemical production. These results validate terpene total as not academic curiosity but also viable alternative isolation or bioengineering efficient preparation polyoxygenated terpenoids at limits complexity.