Halogenated d-xylono-δ-lactams: synthesis and enzyme inhibition study

•The Corey–Link reaction was exploited with 3-keto-d-gluco derived sugar.•New C-3 halogenated d-xylono-δ-lactams were synthesized.•The Schmidt–Boyer reaction was exploited for the synthesis of d-xylono-δ-lactams.•Glycosidase inhibitory activity of halogenated d-xylono-δ-lactams was studied.

A concise synthesis of four C-3 fluoro/chloro-d-xylono-δ-lactams 3/4 has been reported. The methodology involves Corey–Link approach with suitably protected 3-oxo-d-gluco-furanose to introduce F/Cl as well as ester/amide functionalities at C-3 of glucose. In next steps, 5,6-O-isopropylidene group was converted to the 5-azido xylosugars that on opening of 1,2-acetonide group, and intramolecular Schmidt–Boyer reaction with TFA/H2O, in one pot, afforded lactams 3/4. Conformational aspect of δ-lactams was studied by the 1H NMR spectroscopy. The halogenated δ-lactams 3/4 showed no inhibition against different glycosidase enzymes.

Graphical abstractHalogenated d-xylono-δ-lactams were synthesized from commercially available d-glucose by using Corey–Link reaction and intra molecular Schmidt reaction as key steps. The glycosidase inhibition activity and conformational analysis by 1H NMR of these compounds was studied.Figure optionsDownload full-size imageDownload as PowerPoint slide