De novo synthesis of L-DNJ and its N-alkylated derivatives

herein we report a synthetic procedure for the preparation of L-DNJ and its N-alkylated derivatives (FIGURE 1). The highly stereocontrolled access to the iminosugar core has been devised through de novo synthesis starting from the synthetically available homologating agent ,and the Garner aldehyde . In addition, the use of polymer-bound triphenylphosphine/iodine has been conceived for the assembly of the alkyl chains, thereby providing a variety of N-alkyl L-DNJ derivatives. Biological assays for some of these derivatives are also presented, revealing an interesting therapeutic potential in the treatment of some genetic disorders including Pompe disease and Cystic Fibrosis