| 219992-19-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• CAS: 219992-19-5
• 化学式: C₁₃H₁₆O₅
• 分子量: 252.267
• InChiKey: ALEWMEUJGLYSKT-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.55
• 重原子数：
  18.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 sodium tetrahydroborate 、 dimethyl sulfide borane 作用下， 生成 (2R,3S)-2-Benzyl-3,4-dihydroxy-butyric acid methyl ester
  参考文献：
  名称：

  Hydrogen Bonding and Attenuation of the Rate of Enzymic Catalysis

  摘要：

  Hydrogen bonds between a small molecule and an enzyme can potentially contribute significantly to the stability of the complex. Such electrostatic interactions can also lower energy barriers for reactions by solvation of high-energy species. A novel type bf inhibitor is described in this report, which was designed to take advantage of a hydrogen bond that it makes to the active-site histidine of chymotrypsin to attenuate its basicity. Substrates of chymotrypsin acylate the active-site serine (of the catalytic triad), and the acyl-enzyme intermediate undergoes deacylation in a second step of the catalytic turnover. The active-site histidine (of the catalytic triad) serves as the general base in both steps of the turnover process. Such attenuation of basicity by hydrogen bonding was expected to impair catalysis by the enzyme. Two molecules of this type were synthesized that are based on the structure of the chymotrypsin substrate Ac-L-Ala-L-Ala-Gly-L-Phe methyl ester. These were methyl (2R,3R)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (1) and methyl (2R,3S)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (2). Compound 1 acylated chymotrypsin, but the acyl-enzyme species resisted deacylation. On the other hand, compound 2 did not even have the ability to acylate the active-site serine. Molecular modeling supported the assertion that compound 1 makes a critical hydrogen bond to the active-site histidine at the acyl-enzyme stage, whereas compound 2 does so at the preacylation complex. The concepts described herein are of general interest and should find applications for inhibition of enzymes that employ general acid-base chemistry for their catalytic processes.

  DOI：

  10.1021/ja983063e
• 作为产物：
  描述：

  L-苹果酸二甲酯 、 溴甲苯 在 lithium diisopropyl amide 作用下， 生成
  参考文献：
  名称：

  Hydrogen Bonding and Attenuation of the Rate of Enzymic Catalysis

  摘要：

  Hydrogen bonds between a small molecule and an enzyme can potentially contribute significantly to the stability of the complex. Such electrostatic interactions can also lower energy barriers for reactions by solvation of high-energy species. A novel type bf inhibitor is described in this report, which was designed to take advantage of a hydrogen bond that it makes to the active-site histidine of chymotrypsin to attenuate its basicity. Substrates of chymotrypsin acylate the active-site serine (of the catalytic triad), and the acyl-enzyme intermediate undergoes deacylation in a second step of the catalytic turnover. The active-site histidine (of the catalytic triad) serves as the general base in both steps of the turnover process. Such attenuation of basicity by hydrogen bonding was expected to impair catalysis by the enzyme. Two molecules of this type were synthesized that are based on the structure of the chymotrypsin substrate Ac-L-Ala-L-Ala-Gly-L-Phe methyl ester. These were methyl (2R,3R)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (1) and methyl (2R,3S)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (2). Compound 1 acylated chymotrypsin, but the acyl-enzyme species resisted deacylation. On the other hand, compound 2 did not even have the ability to acylate the active-site serine. Molecular modeling supported the assertion that compound 1 makes a critical hydrogen bond to the active-site histidine at the acyl-enzyme stage, whereas compound 2 does so at the preacylation complex. The concepts described herein are of general interest and should find applications for inhibition of enzymes that employ general acid-base chemistry for their catalytic processes.

  DOI：

  10.1021/ja983063e

文献信息

• Enantioselective synthesis of α-hydroxylated enterolactone and analogs
  作者：Michael Sefkow、Alexandra Kelling、Uwe Schilde

  DOI：10.1016/s0040-4039(01)00907-8

  日期：2001.7

  A short and general synthesis of enantiomerically pure α-hydroxylated lactone lignans starting from commercially available iPr malate is presented. Key reactions are two stereoselective alkylations of malic acid derivatives. Some enhancements of the alkylation of malic acid esters and a general extension of the alkylation of dioxolanones is reported. Proof of the stereochemical outcome of the alkylation

  对映体纯α羟基化内酯木脂素从商购的起始短而一般合成我镨苹果酸被呈现。关键反应是苹果酸衍生物的两个立体选择性烷基化。据报道，苹果酸酯的烷基化有一些增强，而二氧戊环酮的烷基化也有普遍的扩展。X-射线衍射分析α-羟基-α，β-二苄基-γ-丁内酯是对映体纯的α-羟基化内酯木脂体的第一个晶体结构，提供了烷基化反应的立体化学结果的证据。