Bicyclic Hybrid Sugars as Glycosidase Inhibitors: Synthesis and Comparative Study of Inhibitory Activities of Fused Oxa-Oxa, Oxa‑Aza, and Oxa-Carbasugar Hybrid Molecules

A few bicyclic hybrid sugar molecules comprising of oxa-aza, oxa-oxa, and oxa-carbasugar fused skeletons were designed and synthesized from C-2 acetoxyglucal involving Ferrier rearrangement, Grignard addition, and ring-closing metathesis as key steps. The inhibitory activities of the synthesized molecules were tested against commercially available enzymes, which revealed the sugar–piperidine and sugar–pyran hybrids as potent and selective inhibitors