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

ABSTRACT

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 ß-galactosidase (IC50=21 µM).