3-Hydroxyazetidine carboxylic acids: non-proteinogenic amino acids for medicinal chemists.

Journal article

The formation from D-glucose of both enantiomers of 2,4-dideoxy-2,4-iminoribonic acid is the first chemical synthesis of unprotected 3-hydroxyazetidine carboxylic acids. The long-term stability of 3-hydroxyazetidine amides is established at acidic and neutral pH and implies their value as non-proteinogenic amino acid components of peptides, providing medicinal chemists with a new class of peptide isosteres. The structure of N,3-O-dibenzyl-2,4-dideoxy-2,4-imino-D-ribonic acid was established by X-ray crystallographic analysis. An N-methylazetidine amide derivative is a specific inhibitor of β-hexosaminidases at the micromolar level, and is only the second example of potent inhibition of any glycosidase by an amide of a sugar amino acid related to an iminosugar.

Authors: Glawar, A; Jenkinson, S; Thompson, A; Nakagawa, S; Kato, A

• Publication status: Published
• Journal: ChemMedChem
• Volume: 8
• Issue: 4
• Pages: 658-666
• Publication date: 2013-04-01
• DOI: 10.1002/cmdc.201200541
• EISSN: 1860-7187
• ISSN: 1860-7179
• Language: English
• Keywords: Imino Sugars; Azetidines; Protein Binding; Molecular Conformation; Structure-Activity Relationship; Stereoisomerism; Enzyme Inhibitors; Crystallography, X-Ray; Animals; Amino Acids; Azetidinecarboxylic Acid; Amides; Humans; Hexosaminidases