IBBR publication #2006

N-Butyl-l-deoxynojirimycin (l-NBDNJ): synthesis of an allosteric enhancer of α-glucosidase activity for the treatment of pompe disease

D’alonzo D, De Fenza M, Porto C, Iacono R, Huebecker M, Cobucci-Ponzano B, Priestman DA, Platt F, Parenti G, Moracci M, Palumbo G, Guaragna A

Journal of Medicinal Chemistry 60 (23): 9462-9469. (2017)
doi: 10.1021/acs.jmedchem.7b00646

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 α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor.