C-5a-substituted validamine type glycosidase inhibitors

A series of N-alkyl derivatives of the D-galactosidase inhibitor 1,4-di-epi-validamine featuring lipophilic substituents at position C-5a was prepared and screened for their glycosidase inhibitory properties. Products turned out selective for β-galactosidases as well as β-glucosidases. [Display omitted] •A simple route enables access to C-5a-hydroxylated derivatives of 1,4-di-epi-validamine.•Regioselective derivatization with a range of isocyanates provides one-step access to lipophilic analogs.•Additional modifications are available by simple 1-N-alkylation.•Final products are inhibitors of β-galactosidases.