A three-component Mannich-type condensation leading to phosphinic dipeptides—extended transition state analogue inhibitors of aminopeptidases

• Published in: Tetrahedron letters Vol. 52; no. 24; pp. 3141 - 3145
• Main Authors: Dziełak, Anna, Pawełczak, Małgorzata, Mucha, Artur
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 15-06-2011; Elsevier
• Subjects: Amines; Amino acids; Aminopeptidases; Analogue; Bearing; Chemistry; Condensing; Exact sciences and technology; Inhibitors; Mannich condensation; Organic chemistry; Peptides; Phosphinomethylation; Preparations and properties; Tetrahedrons; Transition state inhibitors; Utilities; Phosphinomethylation; Mannich condensation; Transition state inhibitors; Aminopeptidases; Phosphinic acids; Phosphorylation; Peptides; Molecular structure; Formaldehyde; Phosphorus Organic compounds; Carboxylic acid; Chemical synthesis; Protection; Secondary amine; Condensation reaction; Multicomponent reaction; Enzyme; Phosphopeptide; Pseudopeptide; Peptidases; Aminoacid; Mannich reaction; Transition state; Dipeptides; Hydrolases; Inhibitor; Methylation
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2011.04.037

N-Protected α-aminoalkylphosphinic acids bearing a P–H function were found to be novel practical building blocks in three-component condensations with formaldehyde and secondary amines (amino acids). Such Mannich-type
N-phosphonomethylation is a common approach for phosphorus acid derived substrates and leads to multifunctional (phosphonic/amino/carboxylic) compounds of diverse relevance. The utility of this reaction was examined for construction, in a single synthetic step, of advanced phosphinic pseudodipeptides designed to act as extended transition state analogue inhibitors of selected aminopeptidases. Phosphinomethylation of primary amino acids was less efficient and yielded mixtures of products which were separated into individual components, and their structures identified.