Looking-Glass Synergistic Pharmacological Chaperones: DGJ and L-DGJ from the Enantiomers of Tagatose

The enantiomers of tagatose are converted to L-DGJ [a noncompetitive inhibitor of human lysosome alpha-galactosidase A (alpha-Gal A), K-i 38.5 mu M] and DGJ [a competitive inhibitor of alpha-Gal A, K-i 15.1 nM] in 66% yield. L-DGJ and DGJ provide the first examples of pharmacological chaperones that (a) are enantiomeric iminosugars and (b) have synergistic activity with implications for the treatment of lysosomal storage disorders and other protein deficiencies.