Synthesis of Diverse Terpenoid Frameworks via Enzyme-Enabled Abiotic Scaffold Hop

Owing to their structural complexity, target-oriented syntheses of natural products usually require the design of individualized routes that are tailor-made for the specific targets. As such, route re-design is needed when targets of different skeletal connectivities are considered. Here, we report a versatile synthetic strategy that runs counter to this conventional wisdom and allows access to a range of terpenoids with distinct skeletal frameworks from the sesquiterpene lactone sclareolide as the starting material. By viewing a biocatalytically-installed alcohol as an exploitable motif rather than a structural endpoint, a number of abiotic skeletal rearrangements were designed, resulting in significant structural divergence from the original drimane ring system of sclareolide. Using this approach, the syntheses of four terpenoid natural products, namely merosterolic acid B, cochlioquinone B, (+)-daucene and dolasta-1(15),8-diene, were achieved.