3-methyl-10-(4-hydroxyphenyl)isoalloxazine | 119100-14-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 3-methyl-10-(4-hydroxyphenyl)isoalloxazine
• 英文别名: Benzo[g]pteridine-2,4(3H,10H)-dione, 10-(4-hydroxyphenyl)-3-methyl-；10-(4-hydroxyphenyl)-3-methylbenzo[g]pteridine-2,4-dione
• CAS: 119100-14-0
• 化学式: C₁₇H₁₂N₄O₃
• 分子量: 320.307
• InChiKey: MKNALTBDBSYVSP-UHFFFAOYSA-N

物化性质

• 熔点：
  >360 °C
• 沸点：
  542.8±52.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  85.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-苯甲基-1,4-二氢烟酰胺 、 3-methyl-10-(4-hydroxyphenyl)isoalloxazine 以 水 为溶剂， 生成 1-benzyl-3-carbamoylpyridinium ion 、
  参考文献：
  名称：

  Flavin Activation by Intramolecular Acid Catalysis at N(1) Position

  摘要：

  为了评估分子内酸催化对特定黄素反应性的影响，合成了3-甲基-10-(2-羟基苯基)异黄素（1(2OH)）和3-甲基-10-(2-羟基-1-萘基)异黄素（2(2OH)），并将其氧化还原性质与参考黄素如3-甲基-10-(2-甲氧基苯基)异黄素（1(2OMe)）和3-甲基-10-(2-甲氧基-1-萘基)异黄素（2(2OMe)）进行了比较。1(2OH)和2(2OH)的pKa值分别为7.7和7.0，均低于3-甲基-10-(4-羟基苯基)异黄素（1(4OH)：pKa 8.6）。因此，在反应的初始状态（即氧化状态）下，2′-OH和N(1)形成氢键的可能性较小。X射线晶体学研究表明，苯环与异黄素环之间的夹角为79.7°，而2′-OH基团与晶体格中包含的甲醇形成氢键。在30 °C的乙腈中，1-苯基-1,4-二氢烟酰胺未被1(2OMe)、1(4OH)和2(2OMe)氧化。另一方面，1(2OH)和2(2OH)（在10-芳基取代基的2′位置具有酸性OH基团）发生了氧化。分子内酸催化的存在表明，2′-OH和N(1)至少可以在反应的过渡态或最终状态（即还原状态）下相互作用。一般来说，氧化的黄素采用“平面”结构，立体张力较大，而还原的黄素则采用“弯曲”结构，立体张力较小。由于过渡态的结构或多或少与还原形式相似，因此在从紧张的初始状态转变为放松的过渡状态时，氢键相互作用可能会增强。这是黄素介导反应中酸催化的新颖例子。

  DOI：

  10.1246/bcsj.61.2095
• 作为产物：
  描述：

  3-methyl-10-(4-methoxyphenyl)isoalloxazine 在 氢溴酸 、 溶剂黄146 作用下， 反应 20.0h， 以69%的产率得到3-methyl-10-(4-hydroxyphenyl)isoalloxazine
  参考文献：
  名称：

  Flavins as potential antimalarials. 2. 3-Methyl-10-(substituted-phenyl)flavins

  摘要：

  A series of 3-methyl-10-(substituted-phenyl)flavins was prepared and tested for antimalarial activity against the lethal parasite Plasmodium vinckei in mice. Several of these analogues were found to be effective antimalarial agents. A quantitative structure-activity relationship study was undertaken with 44 analogues and no satisfactory relationship could be established.

  DOI：

  10.1021/jm00110a009

文献信息

• COWDEN, WILLIAM B.;HALLADAY, PETER K.;CUNNINGHAM, ROSS B.;HUNT, NICHOLAS +, J. MED. CHEM., 34,(1991) N, C. 1818-1822
  作者：COWDEN, WILLIAM B.、HALLADAY, PETER K.、CUNNINGHAM, ROSS B.、HUNT, NICHOLAS +

  DOI：——

  日期：——
• Flavins as potential antimalarials. 2. 3-Methyl-10-(substituted-phenyl)flavins
  作者：William B. Cowden、Peter K. Halladay、Ross B. Cunningham、Nicholas H. Hunt、Ian A. Clark

  DOI：10.1021/jm00110a009

  日期：1991.6

  A series of 3-methyl-10-(substituted-phenyl)flavins was prepared and tested for antimalarial activity against the lethal parasite Plasmodium vinckei in mice. Several of these analogues were found to be effective antimalarial agents. A quantitative structure-activity relationship study was undertaken with 44 analogues and no satisfactory relationship could be established.
• Flavin Activation by Intramolecular Acid Catalysis at N(1) Position
  作者：Seiji Shinkai、Sayuri Kawanabe、Akito Kawase、Toshiro Yamaguchi、Osamu Manabe、Shigeharu Harada、Hideki Nakamura、Nobutami Kasai

  DOI：10.1246/bcsj.61.2095

  日期：1988.6

  In order to assess the effect of intramolecular acid catalysis on the specific flavin reactivities, 3-methyl-10-(2-hydroxyphenyl)isoalloxazine (1(2OH)) and 3-methyl-10-(2-hydroxy-1-naphthyl)isoalloxazine (2(2OH)) were synthesized and the redox properties were compared with those of reference flavins such as 3-methyl-10-(2-methoxyphenyl)isoalloxazine (1(2OMe)) and 3-methyl-10-(2-methoxy-1-naphthyl)isoalloxazine (2(2OMe)). The pKa values for 1(2OH) and 2(2OH) were determined to be 7.7 and 7.0, respectively, which were lower than that of 3-methyl-10-(4-hydroxyphenyl)isoalloxazine (1(4OH): pKa 8.6). It is thus unlikely that 2′-OH and N(1) form a hydrogen bond at the initial state of the reaction (i.e., at the oxidized state). The X-ray crystallographic studies indicated that the phenyl ring makes an angle of 79.7° with the isoalloxazine ring and the 2′-OH group forms a hydrogen bond with methanol included in the crystal lattice. In acetonitrile at 30 °C 1-benzyl-1,4-dihydronicotinamide was not oxidized by 1(2OMe), 1(4OH), and 2(2OMe). On the other hand, the oxidation took place with 1(2OH) and 2(2OH) which have an acidic OH group at the 2′-position of the 10-aryl substituent. The presence of the intramolecular acid catalysis suggests that 2′-OH and N(1) can interact at least at the transition state or at the final state of the reaction (i.e., at the reduced state). In general, the oxidized flavin adopts a “planar” structure which is sterically tense while the reduced flavin adopts a “bent” structure which is sterically relaxed. As the structure of the transition state is more or less similar to the reduced form, the hydrogen-bonding interaction could increase on going from the tense initial state to the relaxed transition state. This is a novel example for acid catalysis in flavin-mediated reactions.

  为了评估分子内酸催化对特定黄素反应性的影响，合成了3-甲基-10-(2-羟基苯基)异黄素（1(2OH)）和3-甲基-10-(2-羟基-1-萘基)异黄素（2(2OH)），并将其氧化还原性质与参考黄素如3-甲基-10-(2-甲氧基苯基)异黄素（1(2OMe)）和3-甲基-10-(2-甲氧基-1-萘基)异黄素（2(2OMe)）进行了比较。1(2OH)和2(2OH)的pKa值分别为7.7和7.0，均低于3-甲基-10-(4-羟基苯基)异黄素（1(4OH)：pKa 8.6）。因此，在反应的初始状态（即氧化状态）下，2′-OH和N(1)形成氢键的可能性较小。X射线晶体学研究表明，苯环与异黄素环之间的夹角为79.7°，而2′-OH基团与晶体格中包含的甲醇形成氢键。在30 °C的乙腈中，1-苯基-1,4-二氢烟酰胺未被1(2OMe)、1(4OH)和2(2OMe)氧化。另一方面，1(2OH)和2(2OH)（在10-芳基取代基的2′位置具有酸性OH基团）发生了氧化。分子内酸催化的存在表明，2′-OH和N(1)至少可以在反应的过渡态或最终状态（即还原状态）下相互作用。一般来说，氧化的黄素采用“平面”结构，立体张力较大，而还原的黄素则采用“弯曲”结构，立体张力较小。由于过渡态的结构或多或少与还原形式相似，因此在从紧张的初始状态转变为放松的过渡状态时，氢键相互作用可能会增强。这是黄素介导反应中酸催化的新颖例子。