Merging chemoenzymatic and radical-based retrosynthetic logic for rapid and modular synthesis of oxidized meroterpenoids

Meroterpenoids are natural products of hybrid biosynthetic origins—derived from both terpenoid and polyketide pathways—with a wealth of biological activities. Given their therapeutic potential, a general strategy to access these natural products in a concise and divergent fashion is highly desirable. Here, we report a modular synthesis of a suite of oxidized meroterpenoids using a hybrid synthetic strategy that is designed to harness the power of both biocatalytic and radical-based retrosynthetic logic. This strategy enables direct introduction of key hydroxyl groups and rapid construction of key bonds and stereocentres, facilitating the development of a concise route (7–12 steps from commercial materials) to eight oxidized meroterpenoids from two common molecular scaffolds. This work lays the foundation for rapid access to a wide range of oxidized meroterpenoids through the use of similar hybrid strategy that combines two synthetic approaches. Meroterpenoids are mixed terpenoid–polyketide natural products that exhibit a range of biological activities. A hybrid synthetic strategy that combines biocatalytic and radical-based methods has now been developed and it enables eight different oxidized meroterpenoids to be made in just 7–12 steps from commercially available materials.