Total Synthesis of the Antibiotic Kendomycin: A Macrocyclization Using the Tsuji-Trost Etherification

摘要

A highly stereocontrolled, convergent total synthesis of kendomycin (—)-TAN2162, an ansa-macrocyclic antibiotic, is reported. The key of the strategy is an unprecedented Tsuji-Trost macrocyclic etherification, followed by a trans-annular Claisen rearrangement to construct the 18-membered carbocyclic framework. The oxa-six- and five-membered rings were also stereoselectively constructed respectively by a cascade oxidative cyclization at an unfunctionalized benzylic position and using a one-pot epoxidation/5-exo-tet epoxide opening.