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3‐Hydroxyazetidine Carboxylic Acids: Non‐Proteinogenic Amino Acids for Medicinal Chemists
Author(s) -
Glawar Andreas F. G.,
Jenkinson Sarah F.,
Thompson Amber L.,
Nakagawa Shinpei,
Kato Atsushi,
Butters Terry D.,
Fleet George W. J.
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200541
Subject(s) - chemistry , amino acid , amide , stereochemistry , enantiomer , carboxylic acid , iminosugar , peptide , derivative (finance) , organic chemistry , biochemistry , enzyme , financial economics , economics
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.