Methyl <1(S)-(1α,3β,4α,5α)>-4-(acetyloxy)-3-<<(benzyloxy)methyl>oxy>-1-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-5-<2-(dimethoxyphosphinyl)ethyl>cyclohexane-1-carboxylate | 160911-99-9

• 分子结构分类: 有机化合物
• 英文名称: Methyl <1(S)-(1α,3β,4α,5α)>-4-(acetyloxy)-3-<<(benzyloxy)methyl>oxy>-1-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-5-<2-(dimethoxyphosphinyl)ethyl>cyclohexane-1-carboxylate
• 英文别名: methyl (1S,3S,4R,5R)-4-acetyloxy-1-[tert-butyl(dimethyl)silyl]oxy-3-(2-dimethoxyphosphorylethyl)-5-(phenylmethoxymethoxy)cyclohexane-1-carboxylate
• CAS: 160911-99-9
• 化学式: C₂₈H₄₇O₁₀PSi
• 分子量: 602.734
• InChiKey: NAPGLDLQJHYTAQ-NXNJFABFSA-N

物化性质

• 沸点：
  591.395±50.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.140±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  40
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Methyl <1(S)-(1α,3β,4α,5α)>-4-(acetyloxy)-3-<<(benzyloxy)methyl>oxy>-1-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-5-<2-(dimethoxyphosphinyl)ethyl>cyclohexane-1-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 methyl (1S,3S,4R,5R)-4-acetyloxy-3-(2-dimethoxyphosphorylethyl)-1-hydroxy-5-(phenylmethoxymethoxy)cyclohexane-1-carboxylate
  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：

  Methyl <1(R)-(1α,4α,5β)>-4-(benzoyloxy)-5-<<(benzyloxy)methyl>oxy>-1-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-2-cyclohexene-1-carboxylate 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 偶氮二异丁腈 、 四溴化碳 、 三正丁基氢锡 、 sodium methylate 、 对甲苯磺酸 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 116.83h， 生成 Methyl <1(S)-(1α,3β,4α,5α)>-4-(acetyloxy)-3-<<(benzyloxy)methyl>oxy>-1-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-5-<2-(dimethoxyphosphinyl)ethyl>cyclohexane-1-carboxylate
  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