Miller Duncan C, Carbain Benoit, Beale Gary S, Alhasan Sari F, Reeves Helen L, Baisch Ulrich, Newell David R, Golding Bernard T, Griffin Roger J
Newcastle Cancer Centre, Northern Institute for Cancer Research, School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.
Org Biomol Chem. 2015 May 14;13(18):5279-84. doi: 10.1039/c5ob00211g.
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.
伯羟基的区域选择性氨磺酰化实现了首个报道的硫酸酯酶 -1 和 -2 的小分子抑制剂（(2S,3R,4R,5S,6R)-4,5 - 二羟基 -2 - 甲氧基 -6 - ((氨磺酰氧基)甲基)四氢 -2H - 吡喃 -3 - 基)氨磺酸）的五步合成（总产率 17%），该合成避免了使用羟基保护基，相较于报道的使用危险的三氟甲基磺酰叠氮的九步合成（总产率 9%）有显著改进。氨磺酰化方法用于制备一系列 1 的衍生物，并生成了针对硫酸酯酶 -2、芳基硫酸酯酶 A 和芳基硫酸酯酶 B 的抑制数据。
