Regioselective sulfamoylation at low temperature enables concise syntheses of putative small molecule inhibitors of sulfatases

Regioselective sulfamoylation of primary hydroxyl groups enabled a 5-step synthesis (overall yield 17%) of the first reported small molecule inhibitor of sulfatase-1 and 2, ((2S, 3R, 4R, 5S, 6R)-4,5-dihydroxy-2-methoxy-6-((sulfamoyloxy)methyl) tetrahydro-2H-pyran-3-yl) sulfamic acid, which obviated the use of hydroxyl protecting groups and is a marked improvement on the reported 9-step synthesis (overall yield 9%) employing hazardous trifluoromethylsulfonyl azide. The sulfamoylation methodology was used to prepare a range of derivatives of 1, and inhibition data was generated for Sulf-2, ARSA and ARSB.