Synthesis of Novel Iminosugar-based Trehalase Inhibitors by Cross-Metathesis Reactions

The synthesis of a novel class of trehalase inhibitors composed of iminopyranose or iminofuranose residues linked at the pseudoanomeric carbon through an alkyl chain is described. A set of six novel compounds was prepared by the same reaction sequence involving the Grubbs Ru–carbenecatalyzed cross-metathesis (CM) of different N-Cbz-protected allyl C-iminoglycosides as the key step in homo- or heterodimerization reactions. The target products, obtained with the CM reaction, were fully hydrogenated by catalytic hydrogenolysis, and preliminary biological screening of the products as inhibitors of commercially available porcine trehalase was performed.