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

ABSTRACT: 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.

SUBMITTER: Richardson AD 

PROVIDER: S-EPMC9401860 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature