Sesquiterpene Backbones Generated by Sesquiterpene Cyclases: Formation of iso-Caryolan-1-ol and an Isoclovane

New sesquiterpene backbones are accessible after incubation of caryolan-synthase (GcoA) and presilphiperfolan-8-beta-ol synthase (BcBOT2) with a non-natural farnesyldiphosphate in which the central olefinic double bond is isomerized toward the methyl group. Two newly formed sesquiterpenoids are reported, a constitutional isomer of caryolan-1-ol (3), which we name iso-caryolan-1-ol (17), and the first terpenoid based on the isoclovane ring skeleton generated enzymatically thus far.