A 14-step synthesis of (+)-cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate. A subsequent Catellani reaction incorporated the remaining carbon atoms featured in the skeleton of cochlearol B. An ensuing visible-light-mediated [2+2] photocycloaddition closed the cyclobutane and formed the central bicyclo-[3.2.0]heptane core. Notably, careful design and tuning of the Catellani and photocycloaddition reactions proved crucial in overcoming undesired reactivity, including cyclopropanation reactions and [4+2] cycloadditions.

Since the first reports of their isolation, the meroterpenoids cochlearol A and B have attracted interest from the synthetic community for their unique structural features. This review describes the attempted and successful total syntheses of these natural products and provides a summary of the strategies developed in the years since their isolation.

A 14-step synthesis of (+)-cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate. A subsequent Catellani reaction incorporated the remaining carbon atoms featured in the skeleton of cochlearol B. An ensuing visible-light-mediated [2+2] photocycloaddition closed the cyclobutane and formed the central bicyclo-[3.2.0]heptane core. Notably, careful design and tuning of the Catellani and photocycloaddition reactions proved crucial in overcoming undesired reactivity, including cyclopropanation reactions and [4+2] cycloadditions.

A new, twelve-step approach towards the meroterpenoid cochlearol B is reported. This strategy takes advantage of a palladium-catalyzed Catellani reaction of a complex chromenyl triflate and a subsequent visible light-mediated [2+2]-cycloaddition to form the central bicyclo[3.2.0]heptane core of cochlearol B. Notably, careful selection and tuning of the photocycloaddition precursor proved crucial to differentiate between cyclopropanation reactions, [4+2] cycloadditions, and selective [2+2]-photocycloadditions.