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.