(1S,3R,4R,5R)-3,4-Bis-benzyloxymethoxy-1,5-dihydroxy-cyclohexanecarboxylic acid | 160912-07-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,3R,4R,5R)-3,4-Bis-benzyloxymethoxy-1,5-dihydroxy-cyclohexanecarboxylic acid
• 英文别名: (1S,3R,4R,5R)-1,3-dihydroxy-4,5-bis(phenylmethoxymethoxy)cyclohexane-1-carboxylic acid
• CAS: 160912-07-2
• 化学式: C₂₃H₂₈O₈
• 分子量: 432.471
• InChiKey: UKXAEIWEJYIBLI-FQOCKNPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1S,3R,4R,5R)-3,4-Bis-benzyloxymethoxy-1,5-dihydroxy-cyclohexanecarboxylic acid 在 palladium on activated charcoal 正丁基锂 、 氢气 、 caesium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， -78.0~25.0 ℃ 、344.73 kPa 条件下， 反应 20.25h， 生成 <1(R)-(1α,3α,4α,5β)>-3-(Phosphonooxy)-1,4,5-trihydroxycyclohexane-1-carboxylic acid
  参考文献：
  名称：

  Inversion of an Asymmetric Center in Carbocyclic Inhibitors of 3-Dehydroquinate Synthase: Examining and Exploiting the Mechanism for syn-Elimination during Substrate Turnover

  摘要：

  Conversion of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) into 3-dehydroquinate (DHQ) by the enzyme DHQ synthase has been proposed to proceed through a step where the phosphate monoester of a reactive intermediate mediates its own elimination. This hypothesis was tested by challenging DHQ synthase with a series of carbocyclic substrate analogues possessing an inverted methine carbon relative to the same asymmetric center in substrate DAHP which loses a proton during elimination of inorganic phosphate. Despite the stereochemical alteration, epicarbocyclic substrate analogues 5-[(phosphonooxy)methyl]-5-deoxyquinate, 5-(phosphonomethyl)-5-deoxyquinate, 5-(phosphonoethyl)-5-deoxyquinate, and 3-(phosphonooxy)quinate inhibited DHQ synthase with respective inhibition constants (K-i) of 30 nM, 55 nM, 30 mu M, and 53 mu M. These inhibitors were synthesized from quinic acid and with the exception of 3-(phosphono oxy)quinate, were assembled via a strategy employing intramolecular, radical cyclization to establish the stereocenter where the (phosphonooxy)methyl, phosphonomethyl, and phosphonoethyl moieties were attached to the carbocyclic ring. The observed diastereomeric promiscuity in the binding of epicarbocyclic substrate analogues by DHQ synthase is consistent with the hypothesized nonenzymic syn-elimination of inorganic phosphate during substrate turnover.

  DOI：

  10.1021/jo00102a025
• 作为产物：
  描述：

  (1S,3R,4R,5R)-3,4-Bis-benzyloxymethoxy-1,5-dihydroxy-cyclohexanecarboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以90%的产率得到(1S,3R,4R,5R)-3,4-Bis-benzyloxymethoxy-1,5-dihydroxy-cyclohexanecarboxylic acid
  参考文献：
  名称：

  Inversion of an Asymmetric Center in Carbocyclic Inhibitors of 3-Dehydroquinate Synthase: Examining and Exploiting the Mechanism for syn-Elimination during Substrate Turnover

  摘要：

  Conversion of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) into 3-dehydroquinate (DHQ) by the enzyme DHQ synthase has been proposed to proceed through a step where the phosphate monoester of a reactive intermediate mediates its own elimination. This hypothesis was tested by challenging DHQ synthase with a series of carbocyclic substrate analogues possessing an inverted methine carbon relative to the same asymmetric center in substrate DAHP which loses a proton during elimination of inorganic phosphate. Despite the stereochemical alteration, epicarbocyclic substrate analogues 5-[(phosphonooxy)methyl]-5-deoxyquinate, 5-(phosphonomethyl)-5-deoxyquinate, 5-(phosphonoethyl)-5-deoxyquinate, and 3-(phosphonooxy)quinate inhibited DHQ synthase with respective inhibition constants (K-i) of 30 nM, 55 nM, 30 mu M, and 53 mu M. These inhibitors were synthesized from quinic acid and with the exception of 3-(phosphono oxy)quinate, were assembled via a strategy employing intramolecular, radical cyclization to establish the stereocenter where the (phosphonooxy)methyl, phosphonomethyl, and phosphonoethyl moieties were attached to the carbocyclic ring. The observed diastereomeric promiscuity in the binding of epicarbocyclic substrate analogues by DHQ synthase is consistent with the hypothesized nonenzymic syn-elimination of inorganic phosphate during substrate turnover.

  DOI：

  10.1021/jo00102a025