Total Synthesis of (+)-Cochlearol B by an Approach Based on a Catellani Reaction and Visible-Light-Enabled [2+2] Cycloaddition

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.

Automated summary

A 14-step synthesis of (+)-cochlearol B, a renoprotective meroterpenoid, was reported. The synthesis involves the use of organocatalytic Kabbe condensation, Catellani reaction, and visible-light-mediated photocycloaddition. The synthesis features a unique core structure with a densely substituted cyclobutane ring.