Synthesis of 2-carboxymethyl polyhydroxyazepanes and their evaluation as glycosidase inhibitors

•Synthesis of seven new polyhydroxylated azepanes was carried out.•Cis- and trans-diols were obtained from an unsaturated azepane.•Determination of the configurations was achieved for each compound by NMR and X-ray diffraction.•Azepanes were assayed for their inhibitory activity toward a range of six commercially available glycosidases.•A selective and good inhibition of β-galactosidase was obtained for one polyhydroxylated azepane.

A series of diastereomeric tetrahydroxylated azepanes featuring a carboxymethyl group at the pseudo-anomeric position have been synthesized from a common unsaturated intermediate. Syn- and anti-dihydroxylation reactions were achieved to yield the target compounds after efficient one-step deprotection of carbamate, ester and acetonide groups simultaneously. Screening of these polyhydroxylated azepanes toward a range of commercially available glycosidases was performed and one of the stereoisomers showed potent and selective inhibition toward β-galactosidase (IC50 = 21 μM).

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