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 carrying a propargyl group by way of the addition of TMS-propargyl Grignard reagent to a N-sulfinylglycosylamine is reported. This compound was coupled via a triazole-tether to various aromatic and heteroaromatic groups, thus providing structures that can be considered as simplified mimics of UDP-Galf, the substrate of GlfT2, a galactofuranosyltransferase present in mycobacteria. These new compounds were evaluated as inhibitors of this enzyme and found to have significant activity (IC50 values in the high M to low mM range) in spite of the absence of the diphospho linkage present in the parent sugar nucleotide.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2y3I69h