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

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 transannular 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. A new construct: The asymmetric total synthesis of the antibiotic kendomycin was accomplished by using a highly stereocontrolled convergent route. The key feature of the synthetic strategy is the construction of an 18‐membered carbocycle based on an intramolecular Tsuji–Trost etherification/transannular Claisen rearrangement sequence. TBS=tert‐butyldimethylsilyl.