(R)-N-(benzyloxycarbonyl)-O-(2-hydroxy-3-phenylpropanoyl)hydroxylamine | 1257267-02-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-N-(benzyloxycarbonyl)-O-(2-hydroxy-3-phenylpropanoyl)hydroxylamine
• 英文别名: phenylmethoxycarbonylamino (2R)-2-hydroxy-3-phenylpropanoate
• CAS: 1257267-02-9
• 化学式: C₁₇H₁₇NO₅
• 分子量: 315.326
• InChiKey: INDIARWCCHBBAC-OAHLLOKOSA-N

物化性质

• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-(benzyloxycarbonyl)-O-(2-hydroxy-3-phenylpropanoyl)hydroxylamine 在 4-二甲氨基吡啶 、 乙酰氯 、 N,N'-二环己基碳二亚胺 、 Enterobacter cloacae P99 β-lactamase 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 28.33h， 生成 1-(R)-(tert-butoxycarbonyl)-2-phenylethyl chloroformate
  参考文献：
  名称：

  Serendipitous Discovery of α-Hydroxyalkyl Esters as β-Lactamase Substrates

  摘要：

  O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates, While the former molecules do not react rapidly with serine beta-lactamases, the latter are quite good substrates of representative class A and C, but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze hydrolysis of these compounds to a mixture of the alpha-hydroxy acid and hydroxamate. Analogous compounds containing aryloxy leaving groups rather that hydroxamates are also substrates. Structure-activity experiments showed that the alpha-hydroxyl group was required for any substantial substrate activity. Although both D- and L-alpha-hydroxy acid derivatives were substrates, the former were preferred. The response of the class C activity to pH and to alternative nucleophiles (methanol and D-phenylalanine) suggested that the same active site functional groups participated in catalysis as for classical substrates. Molecular modeling was employed to explore how the alpha-hydroxy group might interact with the class C beta-lactamase active site. Incorporation of the alpha-hydroxyalkyl moiety into novel inhibitors will be of considerable interest.

  DOI：

  10.1021/bi101071r
• 作为产物：
  描述：

  N-(苄羰氧基)羟基胺 在 吡啶 、 potassium hydrogensulfate 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 121.0h， 生成 (R)-N-(benzyloxycarbonyl)-O-(2-hydroxy-3-phenylpropanoyl)hydroxylamine
  参考文献：
  名称：

  Serendipitous Discovery of α-Hydroxyalkyl Esters as β-Lactamase Substrates

  摘要：

  O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates, While the former molecules do not react rapidly with serine beta-lactamases, the latter are quite good substrates of representative class A and C, but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze hydrolysis of these compounds to a mixture of the alpha-hydroxy acid and hydroxamate. Analogous compounds containing aryloxy leaving groups rather that hydroxamates are also substrates. Structure-activity experiments showed that the alpha-hydroxyl group was required for any substantial substrate activity. Although both D- and L-alpha-hydroxy acid derivatives were substrates, the former were preferred. The response of the class C activity to pH and to alternative nucleophiles (methanol and D-phenylalanine) suggested that the same active site functional groups participated in catalysis as for classical substrates. Molecular modeling was employed to explore how the alpha-hydroxy group might interact with the class C beta-lactamase active site. Incorporation of the alpha-hydroxyalkyl moiety into novel inhibitors will be of considerable interest.

  DOI：

  10.1021/bi101071r

文献信息

• Serendipitous Discovery of α-Hydroxyalkyl Esters as β-Lactamase Substrates
  作者：Ryan B. Pelto、R. F. Pratt

  DOI：10.1021/bi101071r

  日期：2010.12.14

  O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates, While the former molecules do not react rapidly with serine beta-lactamases, the latter are quite good substrates of representative class A and C, but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze hydrolysis of these compounds to a mixture of the alpha-hydroxy acid and hydroxamate. Analogous compounds containing aryloxy leaving groups rather that hydroxamates are also substrates. Structure-activity experiments showed that the alpha-hydroxyl group was required for any substantial substrate activity. Although both D- and L-alpha-hydroxy acid derivatives were substrates, the former were preferred. The response of the class C activity to pH and to alternative nucleophiles (methanol and D-phenylalanine) suggested that the same active site functional groups participated in catalysis as for classical substrates. Molecular modeling was employed to explore how the alpha-hydroxy group might interact with the class C beta-lactamase active site. Incorporation of the alpha-hydroxyalkyl moiety into novel inhibitors will be of considerable interest.