Design and synthesis of iso-allo-DNJ and l-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase

Abstract

A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC₅₀ = 9.3 μM) than the others. Molecular docking study revealed different docking modes of the iso-allo-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.