Beilstein J. Org. Chem.2010,6, No. 21, doi:10.3762/bjoc.6.21
provided lipophilic 1-deoxygalactonojirimycin derivatives which exhibit 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 chemicalchaperones for GM1-gangliosidosis
related β-galactosidase mutants.
Keywords: chemicalchaperones; 1-deoxy-D-galactonojirimycin; iminosugars; lipophilic galactosidase inhibitor; N-modified iminosugars; Introduction
Iminosugars such as compounds 1–4 (Figure 1) have been shown to be potent glycosidase inhibitors and useful tools for the
-galactosidase from green coffee beans. However, the Ki values are still in the low µM range and thus, suitable for use as chemicalchaperones. Gratifyingly, compounds 20 and 22 exhibited IC50 values of 10.9 µM (Ki = 2.0 µM) and 3.26 µM (Ki = 0.72 µM), respectively, with human lysosomal β-galactosidase.
In