5,6-di-O-acetyl-3-deoxy-3-fluoro-α,β-D-galactofuranose | 356533-63-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5,6-di-O-acetyl-3-deoxy-3-fluoro-α,β-D-galactofuranose
• 英文别名: [(2R)-2-acetyloxy-2-[(2S,3R,4S)-3-fluoro-4,5-dihydroxyoxolan-2-yl]ethyl] acetate
• CAS: 356533-63-6
• 化学式: C₁₀H₁₅FO₇
• 分子量: 266.223
• InChiKey: ACIKSOKRZRLZAM-NZDCWBGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5,6-di-O-acetyl-3-deoxy-3-fluoro-α,β-D-galactofuranose 在 吡啶 、 三甲基溴硅烷 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 20.0h， 生成 dibenzyl (2,5,6-tri-O-acetyl-3-deoxy-3-fluoro-α-D-galactofuranosyl)phosphate
  参考文献：
  名称：

  Mechanistic Investigation of UDP-Galactopyranose Mutase from Escherichia coli Using 2- and 3-Fluorinated UDP-Galactofuranose as Probes

  摘要：

  The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by UDP-Galp mutase. This enzyme, which has been isolated from several bacterial sources, is a flavoprotein. To study this catalysis, the cloned Escherichia coli mutase was purified and two fluorinated analogues, UDP-[2-F]Galf(9) and UDP-[3-F]Galf(10), were chemically synthesized. These two compounds were found to be substrates for the reduced UDP-Galp mutase with the K-m values determined to be 65 and 861 muM for 9 and 10, respectively, and the corresponding k(cat) values estimated to be 0.033 and 5.7 s(-1). Since the fluorine substituent is redox inert, a mechanism initiated by the oxidation of 2-OH or 3-OH on the galactose moiety can thus be firmly ruled out. Furthermore, both 9 and 10 are poorer substrates than UDP-Galf, and the rate reduction for 9 is especially significant. This finding may be ascribed to the inductive effect of the 2-F substituent that is immediately adjacent to the anomeric center, and is consistent with a mechanism involving formation of oxocarbenium intermediates or transition states during turnover. Interestingly, under nonreducing conditions, compounds 9 and 10 are not substrates, but instead are inhibitors for the mutase. The inactivation by 10 is time-dependent, active-site-directed. and irreversible with a K-I of 270 muM and a k(inact) of 0.19 min(-1). Since the K-I value is similar to K-m, the observed inactivation is unlikely a result of tight binding. To our surprise, the inactivated enzyme could be regenerated in the presence of dithionite, and the reduced enzyme is resistant to inactivation by these fluorinated analogues. It is possible that reduction of the enzyme-bound FAD may induce a conformational change that facilitates the breakdown of the putative covalent enzyme-inhibitor adduct to reactivate the enzyme. It is also conceivable that the reduced flavin bears a higher electron density at N-1, which may play a role in preventing the formation of the covalent adduct or facilitating its breakdown by charge stabilization of the oxocarbenium intermediates/transition states. Clearly, this study has led to the identification of a potent inactivator (10) for this enzyme, and study of its inactivation has also shed light on the possible mechanism of this mutase.

  DOI：

  10.1021/ja010473l
• 作为产物：
  描述：

  1,2:5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-galactofuranose 在 吡啶 作用下， 反应 8.42h， 生成 5,6-di-O-acetyl-3-deoxy-3-fluoro-α,β-D-galactofuranose
  参考文献：
  名称：

  Mechanistic Investigation of UDP-Galactopyranose Mutase from Escherichia coli Using 2- and 3-Fluorinated UDP-Galactofuranose as Probes

  摘要：

  The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by UDP-Galp mutase. This enzyme, which has been isolated from several bacterial sources, is a flavoprotein. To study this catalysis, the cloned Escherichia coli mutase was purified and two fluorinated analogues, UDP-[2-F]Galf(9) and UDP-[3-F]Galf(10), were chemically synthesized. These two compounds were found to be substrates for the reduced UDP-Galp mutase with the K-m values determined to be 65 and 861 muM for 9 and 10, respectively, and the corresponding k(cat) values estimated to be 0.033 and 5.7 s(-1). Since the fluorine substituent is redox inert, a mechanism initiated by the oxidation of 2-OH or 3-OH on the galactose moiety can thus be firmly ruled out. Furthermore, both 9 and 10 are poorer substrates than UDP-Galf, and the rate reduction for 9 is especially significant. This finding may be ascribed to the inductive effect of the 2-F substituent that is immediately adjacent to the anomeric center, and is consistent with a mechanism involving formation of oxocarbenium intermediates or transition states during turnover. Interestingly, under nonreducing conditions, compounds 9 and 10 are not substrates, but instead are inhibitors for the mutase. The inactivation by 10 is time-dependent, active-site-directed. and irreversible with a K-I of 270 muM and a k(inact) of 0.19 min(-1). Since the K-I value is similar to K-m, the observed inactivation is unlikely a result of tight binding. To our surprise, the inactivated enzyme could be regenerated in the presence of dithionite, and the reduced enzyme is resistant to inactivation by these fluorinated analogues. It is possible that reduction of the enzyme-bound FAD may induce a conformational change that facilitates the breakdown of the putative covalent enzyme-inhibitor adduct to reactivate the enzyme. It is also conceivable that the reduced flavin bears a higher electron density at N-1, which may play a role in preventing the formation of the covalent adduct or facilitating its breakdown by charge stabilization of the oxocarbenium intermediates/transition states. Clearly, this study has led to the identification of a potent inactivator (10) for this enzyme, and study of its inactivation has also shed light on the possible mechanism of this mutase.

  DOI：

  10.1021/ja010473l