Phosphoenolpyruvamides. Amide-Phosphate Interactions in Analogues of Phosphoenolpyruvate

Article abstract of DOI:10.1021/ja00326a022

Ethyl esters of nitrogen-substituted carboxamides of phosphoenolpyruvate (1 and 2) were obtained from the reactions of triethyl phosphite with the corresponding nitrogen-substituted 3-bromopyruvamide.The hydrolysis of the ethyl ester portions of 1 and 2 occurs with an observed first-order rate constant that is 4 orders of magnitude larger than is estimated for triethyl phosphate under comparable conditions, indicating that participation by the neighboring carboxamide group is occurring.However, the enol phosphate ester substituent is cleaved much more slowly than are vinyl phosphate esters.The results are consistent with a mechanism in which the amide adds to the adjacent phosphate to form a reactive cyclic intermediate.The data support the proposal that amides can become phosphorylated during process that involve interactions of peptides and nucleotides or during phosphate-transfer process.The hydrolysis products of 1 and 2 may also be useful analogues of phosphoenolpyruvate in studies of enzyme mechanisms and in the design of inhibitors.