Work

Synthesis of an N ‐Galactosyl Norbornane Aziridine and its Potent Mixed Inhibition of Aspergillus oryzae β‐Galactosidase

Year: 2025

Type: article

Abstract: Aziridine‐bearing cyclic polyols are established as irreversible covalent inhibitors of glycosyl hydrolases and have been employed as activity‐based probes. In the present study, the stereoselective synthesis of a novel N ‐galactosyl aziridine derivative on a norbornane scaffold and its subsequent evaluation as an inhibitor of glycosyl hydrolase activity are described. The diastereoselective Huisgen cycloaddition between 2,3,4,6‐tetra‐ O ‐acetyl‐β‐ d ‐galactopyranosyl azide and norbornene yields exo ‐triazoline intermediates of norbornane. Following the removal of the acetyl protecting groups and a silica gel‐mediated decomposition of the triazoline intermediates, exo N ‐galactopyranosyl norbornane aziridine ( N ‐(β‐ d ‐galactopyranosyl)‐ exo ‐3‐azatricyclo[3.2.1.0 2,4 ]octane, NGNA) is obtained. Enzymatic assays demonstrate that NGNA exerts potent mixed‐mode inhibition of Aspergillus oryzae β‐galactosidase, while exhibiting significant selectivity over green coffee bean α‐galactosidase.

Source: ChemBioChem

DOI: 10.1002/cbic.202500623

Authors: Aaron McCormack, Ronan Gavin, Mikael Bols, Paul V. Murphy

Institutions: University of Copenhagen, Ollscoil na Gaillimhe – University of Galway

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,430

Funder: Irish Centre for High-End Computing