N-Butyl-L-deoxynojirimycin (L-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease

The highly stereocontrolled de novo synthesis of L-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. L-NBDNJ is able to enhance lysosomal alpha-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human alpha-glucosidase. In addition, differently from its D-enantiomer, L-NBDNJ does not act as a glycosidase inhibitor.