74084-18-7Relevant academic research and scientific papers
Unexpected hydrolytic instability of N-acylated amino acid amides and peptides
Samaritoni, J. Geno,Copes, Alexus T.,Crews, Demarcus K.,Glos, Courtney,Thompson, Andre L.,Wilson, Corydon,O'Donnell, Martin J.,Scott, William L.
, p. 3140 - 3151 (2014/05/06)
Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent's Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis.
Synthesis of Acylamino Acid Amides and Acylamino Acids via 2,4-Disubstituted 2-Imidazolin-5-ones
Devasia, Ganapathiplackal M.,Shafi, P. Mohamed
, p. 70 - 72 (2007/10/02)
Unsaturated 2,4-disubstituted 2-imidazolin-5-ones (I) have been reduced with a mixture of hydriodic acid and red phosphorus in the presence of acetic anhydride to give the saturated 2,4-disubstituted 2-imidazolin-5-ones (II) which have been hydrolysed to acylamino acid amides (III) and acylamino acids (IV) with sodium hydroxide solution under different conditions.In all six acylamino acid amides (23 - 51percent yields) and four acylamino acids (26 - 65percent yields) have been prepared.One saturated 2-imidazolin-5-one, namely 2-phenyl-4-benzyl-2-imidazolin-5-one has been isolated from the reaction in 40percent yield and identified.
