Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors

Abstract N -Alkylation at the ring nitrogen of the D-galactosidase inhibitor 1-deoxygalactonojirimycin with a functionalised C 6 alkyl chainfollowed by modification with different aromatic substituents provided lipophilic 1-deoxygalactonojirimycin derivatives which ex-hibit inhibitory properties against β-glycosidases from E. coli and Agrobacterium sp. as well as green coffee bean α-galactosidase.In preliminary studies, these compounds also showed potential as chemical chaperones for GM1-gangliosidosis relatedβ-galactosidase mutants. Introduction Iminosugars such as compounds 1 – 4 (Figure€1) have beenshown to be potent glycosidase inhibitors and useful tools forthe study of glycoside-hydrolysing enzymes. These sugarmimetics have been found to have anti-viral, anti-cancer, anti-diabetes, anti-infective, as well as insect anti-feedant and plantgrowth regulatory effects. Because of their diverse properties,iminosugars have enjoyed continuous interest since theirdiscovery in the 1960s. Consequently, many different