title: Regioselective sulfamoylation at low temperature enables concise syntheses of putative small molecule inhibitors of sulfatases.
abstract: 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.
authors: Newcastle Cancer Centre, Northern Institute for Cancer Research, School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK. bernard.golding@newcastle.ac.uk.
authors: Duncan C
authors: DC
authors: Miller
authors: Benoit
authors: B
authors: Carbain
authors: Gary S
authors: GS
authors: Beale
authors: Sari F
authors: SF
authors: Alhasan
authors: Helen L
authors: HL
authors: Reeves
authors: Ulrich
authors: U
authors: Baisch
authors: David R
authors: DR
authors: Newell
authors: Bernard T
authors: BT
authors: Golding
authors: Roger J
authors: RJ
authors: Griffin
mesh_terms: D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013429:Sulfatases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D013429:Sulfatases