Amide bond cleavage: acceleration due to a 1,3-diaxial interaction with a carboxylic acid.
To independently assess the contribution of ground-state pseudoallylic strain to the enormous rates of amide bond cleavage in tertiary amide derivatives of Kemp's triacid, we have studied four amide derivatives of (1alpha-3alpha-5beta)-5-tert-butyl-1,3-cyclohexanedicarboxylic acid. Our results demonstrate that absent pseudoallylic strain, a 1,3-diaxial interaction of an amide with a carboxylic acid leads to only a 2400-fold increase in the rate of amide bond cleavage as compared with the rate of hydrolysis of an unactivated peptide bond.
Gerschler
Jared J
JJ
Department of Chemistry, Amherst College, Amherst, Massachusetts 01002, USA.
Wier
Kevin A
KA
Hansen
David E
DE
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013997:Time Factors
D000577:Amides; D002264:Carboxylic Acids