2-Acetamido-2-deoxy-l-iminosugar C-Alkyl and C-Aryl Glycosides: Synthesis and Glycosidase Inhibition

The synthesis of a series of six-membered 2-acetamido l-iminosugar C-alkyl and C-aryl glycosides is reported. A diastereoselective sugar-ring enlargement/C-alkylation (or arylation) /ring-contraction sequence applied to d-gluco- and d-manno-configured 2-acetamido azidolactols provides new l-iminosugar C-glycosides. The 1,2-trans stereocontrolled introduction of the pseudoanomeric substituent in these heterocycles strongly suggests a NHAc neighbouring-group participation. In their deprotected form, the nine iminosugars exhibit moderate hexosaminidases and β-glucuronidase inhibition.