Synthesis of cryptophycins via an N-acyl-beta-lactam macrolactonization.
An efficient and concise approach to the synthesis of the macrolide core of the cryptophycins has been developed. A novel macrolactonization utilizing a reactive acyl-beta-lactam intermediate incorporates the beta-amino acid moiety within the 16-membered macrolide core. This modular approach, involving a cyanide-initiated acyl-beta-lactam ring opening followed by cyclization, was successfully applied to the total synthesis of cryptophycin-24. The strategy was also used in an efficient synthesis of the 6,6-dimethyl-substituted dechlorocryptophycin-52. In this case, the cyanide-initiated ring opening of the bis-substituted 2-azetidinone followed by macrolactonization was achieved through a catalytic process.
Vidya
Ramdas
R
Department of Medicinal Chemistry and Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
Eggen
MariJean
M
Nair
Sajiv K
SK
Georg
Gunda I
GI
Himes
Richard H
RH
D000215:Acylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001384:Azetidines / Q000138:chemical synthesis; D002713:Chlorine / Q000737:chemistry; D047630:Depsipeptides; D007783:Lactones / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
C116379:2-azetidinone; D000970:Antineoplastic Agents; D001384:Azetidines; D047630:Depsipeptides; D007783:Lactones; D010456:Peptides, Cyclic; C096566:arenastatin A; D047090:beta-Lactams; C088419:cryptophycin; D002713:Chlorine