Rapid entry into the cryptophycin core via an acyl-β-lactam macrolactonization: Total synthesis of cryptophycin-24

(formula presented) An efficient, concise approach to the macrolide core of the cryptophycins, potent antimitotic agents, has been achieved. The reaction sequence features a novel macrolactonization utilizing a reactive acyl-β-lactam intermediate that incorporates the β-amino acid moiety within the 16-membered macrolide core. This highly modular approach, which allows for multiple alterations throughout the structure, was successfully applied to the total synthesis of cryptophycin-24.