Synthesis of diverse terpenoid frameworks via enzyme-enabled abiotic scaffold hop

Abstract

Due to the structural complexity of natural products, their target-oriented syntheses usually require the design of individualized routes that are tailor-made for the specific targets. As such, route redesign 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 substantial 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.