6-deoxy-6-dihydrogenophosphono-D-arabinono-1,4-lactone | 1194397-06-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-deoxy-6-dihydrogenophosphono-D-arabinono-1,4-lactone
• CAS: 1194397-06-2
• 化学式: C₆H₁₁O₇P
• 分子量: 226.123
• InChiKey: MGILTUDMECAILE-WDCZJNDASA-N

反应信息

• 作为反应物：
  描述：

  6-deoxy-6-dihydrogenophosphono-D-arabinono-1,4-lactone 在 羟胺 作用下， 以 水 为溶剂， 反应 0.33h， 以100%的产率得到5-deoxy-5-phosphonomethyl-D-arabinonohydroxamic acid dihydroxylammonium salt
  参考文献：
  名称：

  Synthesis and evaluation of non-hydrolyzable d-mannose 6-phosphate surrogates reveal 6-deoxy-6-dicarboxymethyl-d-mannose as a new strong inhibitor of phosphomannose isomerases

  摘要：

  Non-hydrolyzable D-mannose 6-phosphate analogues in which the phosphate group was replaced by a phosphonomethyl, a dicarboxymethyl, or a carboxymethyl group were synthesized and kinetically evaluated as substrate analogues acting as potential inhibitors of type I phosphomannose isomerases (PMIs) from Saccharomyces cerevisiae and Escherichia coli. While 6-deoxy-6-phosphonomethyl-D-mannose and 6-deoxy-6-carboxymethyl-D-mannose did not inhibit the enzymes significantly, 6-deoxy-6-dicarboxymethyl-D-mannose appeared as a new strong competitive inhibitor of both S. cerevisiae and E. coli PMIs with K-m/K-i ratios of 28 and 8, respectively. We thus report the first malonate-based inhibitor of an aldose-ketose isomerase to date. Phosphonomethyl mimics of the 1,2-cis-enediolate high-energy intermediate postulated for the isomerization reaction catalyzed by PMIs were also synthesized but behave as poor inhibitors of PMIs. A polarizable molecular mechanics (SIBFA) study was performed on the complexes of D-mannose 6-phosphate and two of its analogues with PMI from Candida albicans, an enzyme involved in yeast infection homologous to S. cerevisiae and E. coli PMIs. It shows that effective binding to the catalytic site occurs with retention of the Zn(II)-bound water molecule. Thus the binding of the hydroxyl group on C1 of the ligand to Zn(II) should be water-mediated. The kinetic study reported here also suggests the dianionic character of the phosphate surrogate as a likely essential parameter for strong binding of the inhibitor to the enzyme active site. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.005
• 作为产物：
  描述：

  (2S,3R,4R)-2,3,4-trihydroxy-6-phosphonohexanoic acid 生成 6-deoxy-6-dihydrogenophosphono-D-arabinono-1,4-lactone
  参考文献：
  名称：

  Synthesis and evaluation of non-hydrolyzable d-mannose 6-phosphate surrogates reveal 6-deoxy-6-dicarboxymethyl-d-mannose as a new strong inhibitor of phosphomannose isomerases

  摘要：

  Non-hydrolyzable D-mannose 6-phosphate analogues in which the phosphate group was replaced by a phosphonomethyl, a dicarboxymethyl, or a carboxymethyl group were synthesized and kinetically evaluated as substrate analogues acting as potential inhibitors of type I phosphomannose isomerases (PMIs) from Saccharomyces cerevisiae and Escherichia coli. While 6-deoxy-6-phosphonomethyl-D-mannose and 6-deoxy-6-carboxymethyl-D-mannose did not inhibit the enzymes significantly, 6-deoxy-6-dicarboxymethyl-D-mannose appeared as a new strong competitive inhibitor of both S. cerevisiae and E. coli PMIs with K-m/K-i ratios of 28 and 8, respectively. We thus report the first malonate-based inhibitor of an aldose-ketose isomerase to date. Phosphonomethyl mimics of the 1,2-cis-enediolate high-energy intermediate postulated for the isomerization reaction catalyzed by PMIs were also synthesized but behave as poor inhibitors of PMIs. A polarizable molecular mechanics (SIBFA) study was performed on the complexes of D-mannose 6-phosphate and two of its analogues with PMI from Candida albicans, an enzyme involved in yeast infection homologous to S. cerevisiae and E. coli PMIs. It shows that effective binding to the catalytic site occurs with retention of the Zn(II)-bound water molecule. Thus the binding of the hydroxyl group on C1 of the ligand to Zn(II) should be water-mediated. The kinetic study reported here also suggests the dianionic character of the phosphate surrogate as a likely essential parameter for strong binding of the inhibitor to the enzyme active site. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.005