Triazole‐Linked Iminosugars and Aromatic Systems as Simplified UDP‐Galf Mimics: Synthesis and Preliminary Evaluation as Galf‐Transferase Inhibitors

The convenient preparation of 1,4‐dideoxy‐1,4‐imino‐l‐arabinitol derivatives bearing a propargyl group through the addition of a trimethylsilylpropargyl Grignard reagent to an N‐sulfinylglycosylamine is reported. One of these compounds was coupled by a triazole tether to various aromatic and heteroaromatic groups to give structures that can be considered to be simplified mimics of UDP‐Galf, the substrate of GlfT2, a galactofuranosyltransferase present in mycobacteria. The new compounds were evaluated as inhibitors of this enzyme and were found to have significant activity (IC50 values in the high µm to low mm range), despite the absence of the diphospho linkage present in the parent sugar nucleotide. The convenient preparation of 1‐C‐propargyl‐imino‐l‐arabinitol derivatives coupled by a triazole tether to various aromatic and heteroaromatic groups is reported. These structures, which can be considered to be simplified mimics of UDP‐Galf, the substrate of GlfT2, a galactofuranosyltransferase present in mycobacteria, were evaluated as inhibitors of the enzyme and were found to have significant activity.