A Divergent Approach to (+)-Habiterpenol and (−)-Corey’s Protolimonoid

A concise and divergent enantioselective strategy has been developed for the total synthesis of the meroterpenoid (+)-habiterpenol and the formal synthesis of (-)-Corey's protolimonoid. The route originates from a readily available Hajos-Parrish ketone derivative and exploits a highly efficient iterative Robinson annulation sequence to assemble the A/B/C/D tetracyclic core in only four steps. This tetracyclic scaffold serves as a versatile divergent intermediate, enabling completion of (+)-habiterpenol in a 10-step longest linear sequence. Key features include a late-stage aromatization via formylation followed by Michael addition-aldol condensation and copper-mediated oxidation. The synthetic utility of the common tetracyclic intermediate is further demonstrated by its conversion into a known limonoid precursor, constituting a 7-step formal synthesis of (-)-Corey's protolimonoid. Overall, this work highlights a flexible and efficient platform for accessing complex meroterpenoid and terpenoid architectures from a common precursor.