Rapid entry into the cryptophycin core via an acyl-beta-lactam macrolactonization: total synthesis of cryptophycin-24.
[see structure]. 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-beta-lactam intermediate that incorporates the beta-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.
Eggen
M
M
Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, USA.
Nair
S K
SK
Georg
G I
GI
D047630:Depsipeptides; D008938:Mitosis / Q000187:drug effects; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047090:beta-Lactams / Q000737:chemistry*
D047630:Depsipeptides; D010456:Peptides, Cyclic; D047090:beta-Lactams; C088419:cryptophycin