The Synthesis of Azapeptidomimetic β-Lactam Molecules as Potential Protease Inhibitors

Abstract

Synthetic methods for the construction of a novel peptidomimetic structure are reported. The structure incorporates a beta-lactam and an azapeptide in a peptide backbone with the intention of generating rationally designed substrate-based protease inhibitors. The beta-lactam is formed by subjecting serine or threonine-azapeptides to Mitsunobu reaction conditions. Importantly, the azapeptidomimetic beta-lactam structure permits extended binding inhibition and the synthetic methods to create tetrapeptidomimetic structures are described.

N‐Acylhydrazines: Future Perspectives Offered by New Syntheses and Chemistry

“…Malachowski [34] has recently reported the synthesis of a conceptually new azapeptidomimetic in which an N-amino-β-lactam moiety is incorporated in the peptide backbone. In particular, the authors synthesised the tetrapeptidomimetic 42 as a potential second-generation protease inhibitor.…”

Synthesis of 1‐Amino‐1H‐indole‐3‐carboxylates by Copper(I)‐Catalyzed Intramolecular Amination of Aryl Bromides

“…TLC was carried out on silica gel 60 F254 plates (Merck), and the spots were located with UV light. Methyl 2-(2-bromophenyl)-2-formylacetate (1a), [17] methyl 2-(2-bromo-5-methoxyphenyl)-2-formylacetate (1b), [17] tert-butyl 1-methylhydrazinecarboxylate (2b), [18] tert-butyl 1-(4-chlobenzyl)hydrazinecarboxylate (2f), [14] and tert-butyl 1-phenylhydrazinecarboxylate (2g) [15] were prepared in accordance with previously reported procedures.…”

Update 1 of: Beta-Strand Mimetics

“…Aza-amino acids confer unique conformational properties to the peptide backbone. The conformational effects of other variations, such as the incorporation of an aza group within -lactams 185 and aza-peptide Michael acceptors, 186 have not yet been fully explored. The conformational effects of other variations, such as the incorporation of an aza group within -lactams 185 and aza-peptide Michael acceptors, 186 have not yet been fully explored.…”