Synthesis of the Kedarcidin Core Structure by a Transannular Cyclization Pathway

The chromoprotein enediyne antibiotic kedarcidin has a structurally complex and highly reactive chromophore component. An enantioselective synthesis of compound 1, which contains the full functionality of the chromophore core, is described. The key step in the synthetic route involves low-temperature halogen–lithium exchange initiated transannular cyclization of the macrocyclic vinyl bromide 2. TBS=tert-butyldimethylsilyl.