108694-84-4Relevant academic research and scientific papers
Intramolecular Acylolysis of Amide Derivatives of Kemp's Triacid: Strain Effects and Reaction Rates
Curran, Timothy P.,Borysenko, Christopher W.,Abelleira, Susan M.,Messier, Renee J.
, p. 3522 - 3529 (2007/10/02)
Intramolecular acylolysis of comparable secondary and tertiary amide derivatives of Kemp's triacid, 4, and its cis,trans isomer 5 has been examined.For both triacids, the tertiary amide derivatives undergo acylolysis about 1000 times faster than the corresponding secondary amide.Also, amide derivatives of Kemp's triacid undergo acylolysis about 100 times faster than the corresponding amide derivatives of the cis,trans isomer.Thus, acylolysis rates spanning a range of nearly 1E6 are observed.It is proposed that the large rate difference between secondary and tertiary amides in these molecules results from greater pseudoallylic (pseudo-A1,3) strain associated with the tertiary amides.It also is proposed that the slower acylolysis rates observed with amide derivatives of the cis,trans isomer of Kemp's triacid result from greater 1,3-diaxial strain associated with acylolysis of these compounds.The data show that both the structure of the triacid and the structure of the amide have a direct effect on the acylolysis rate.Because previous studies only focused on the structure of the triacid, the proposal that intramolecular acylolysis of amide derivatives of Kemp's triacid is a useful model system for studying enzyme catalysis (Menger, F.M.; Ladika, M.J.Am.Chem.Soc. 1988, 110, 6794.Menger, F.M.Biochemistry 1992, 31, 5368) is reexamined.
Fast Hydrolysis of an Aliphatic Amide at Neutral pH and Ambient Temperature. A Peptidase Model
Menger, F. M.,Ladika, M.
, p. 6794 - 6796 (2007/10/02)
An intramolecular-catalysed cleavage of an aliphatic amide under biological conditions (ambient temperature, neutral pH, absence of alien transition metals) was found to occur with the fastest rate yet recorded for such a reaction: t1/2 = 8 min (pD=7.05, 21.5 deg C) and an effective molarity EM>1E14 M.The peptidase "model" has a carboxyl oxygen perched above the plane of the amide carbonyl at a van der Waals contact distance of 2.8 Angstroem.The carboxyl is poised for synchronous nucleophilic attack and proton delivery.Evidence (based on the observation that the amide actually cleaves much faster than the corresponding methyl ester) suggest that proton transfer plays a key role in the rate-determining step.The results show that an enzyme need not employ esoteric mechanisms to cleave an unreactive entity such as an amide.If the enzyme merely positions a carboxyl adjacent to an amide substrate with the geometry established in the "model", most of the necessary catalytic power would be achieved.
