An improved methodology for the synthesis of 1-C-allyl imino-D-xylitol and -L-arabinitol and their rapid functionalization

As part of our research program dedicated to the design and synthesis of new iminosugars as pharmacological chaperones for the treatment of lysosomal storage disorders, we developed a rapid and efficient methodology for the access to functionalized and non-functionalized 1-C-alkylated derivatives in the D-xylo and L-arabino series. These compounds, as gluco and galacto mimics, were designed to be potent inhibitors of, respectively, beta-glucocerebrosidase, involved in Gaucher disease, and beta-galactocerebrosidase, responsible for Krabbe disease. The key step of the synthesis is the diastereoselective addition of allyltrimethylsilane to the D-xylo or L-arabino N-benzyloxycarbonyl protected glycopyranosylamine. This protective group allows the direct functionalization of the obtained iminosugars using metathesis or oxidation reactions. For determination of the absolute configuration of dihydroxylation reaction products the in situ dimolybdenum methodology of electronic circular dichroism spectroscopy was successfully used. (C) 2013 Elsevier Ltd. All rights reserved.