6(R)-methyl-4a-hydroxytetrahydrobiopterin | 294885-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6(R)-methyl-4a-hydroxytetrahydrobiopterin
• 英文别名: (6S)-2-amino-4a-hydroxy-6-methyl-3,5,6,7-tetrahydropteridin-4-one
• CAS: 294885-50-0
• 化学式: C₇H₁₁N₅O₂
• 分子量: 197.197
• InChiKey: LRQOEVGTDREQQD-NSJQTVLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6(R)-methyl-4a-hydroxytetrahydrobiopterin 在 三羟甲基氨基甲烷盐酸盐 作用下， 生成 (S)-2-Amino-6-methyl-7,8-dihydro-6H-pteridin-4-one
  参考文献：
  名称：

  Synthesis of 4a-Hydroxytetrahydropterins and the Mechanism of Their Nonenzymic Dehydration to Quinoid Dihydropterins

  摘要：

  4a-Hydroxytetrahydropterins 2 (R = Me, Pr, and 1'(R),2'(S)-dihydroxypropyl) were synthesized by intramolecular Schiff base condensation of 2'-substituted 2-amino-6-[(aminoethyl)amino]-4,5-pyrimidinediones 6. The rate vs pH of cyclization of 6 (which is predominately monohydrated) follows a bell-shaped curve with maxima at pH 9.8 in H2O (consistent with pK values of 8.8 and 10.8) and pH 9.1 in MeOH. Although almost insignificant in organic solvents, substantial 7-substituted dihydropterin was generated in water, particularly with 6 (R = dihydroxypropyl). The minimum rate of dehydration of carbinolamine 2 (R = Me or Pr) in ''zero'' buffer (0.0035 s(-1) at 17 degrees C) occurs at pH 8.25, and is catalyzed by proton (1.3 x 10(5) M(-1) s(-1)) and general acids. Between pH 8.4 and pH 7.4 Delta H* decreases from 15 to 12 kcal/mol, while Delta S* decreases from -18 to -26 eu for 2 (R = Me or Pr), consistent with concerted proton transfer in the dehydration transition state. Surprisingly, the rate also increases in more alkaline conditions up to 12-fold (in zero buffer), coincident with formation of a pteridine anion (pK = 9.8). Below pH 11.5 catalysis by buffer base was also observed. A solvent kinetic isotope effect (k(H2O)/k(D2O)) of 2.6, 2.2, and 3.5 was found in dilute buffers at pH 7.4, 8.2, and 10.9, respectively. The overall rate of disappearance of 2 (R = dihydroxypropyl) is similar to that of the alkyl analogs, but a second pathway competes with dehydration to produce a compound tentatively identified as a side-chain 4a-cyclic adduct, which subsequently decays to quinoid 6(R)-dihydrobiopterin. These synthetic substrates have permitted the first kinetic characterization of 4a-hydroxytetrahydropterin dehydratase (Rebrin, I.; et al. Biochemistry 1995, 34, 5801-5810), the enzyme involved in cofactor regeneration during aromatic amino acid hydroxylation.

  DOI：

  10.1021/ja00146a005
• 作为产物：
  描述：

  2-Amino-6-((S)-2-amino-propylamino)-pyrimidine-4,5-dione 在 硼酸三钠 作用下， 生成 6(R)-methyl-4a-hydroxytetrahydrobiopterin
  参考文献：
  名称：

  Synthesis of 4a-Hydroxytetrahydropterins and the Mechanism of Their Nonenzymic Dehydration to Quinoid Dihydropterins

  摘要：

  4a-Hydroxytetrahydropterins 2 (R = Me, Pr, and 1'(R),2'(S)-dihydroxypropyl) were synthesized by intramolecular Schiff base condensation of 2'-substituted 2-amino-6-[(aminoethyl)amino]-4,5-pyrimidinediones 6. The rate vs pH of cyclization of 6 (which is predominately monohydrated) follows a bell-shaped curve with maxima at pH 9.8 in H2O (consistent with pK values of 8.8 and 10.8) and pH 9.1 in MeOH. Although almost insignificant in organic solvents, substantial 7-substituted dihydropterin was generated in water, particularly with 6 (R = dihydroxypropyl). The minimum rate of dehydration of carbinolamine 2 (R = Me or Pr) in ''zero'' buffer (0.0035 s(-1) at 17 degrees C) occurs at pH 8.25, and is catalyzed by proton (1.3 x 10(5) M(-1) s(-1)) and general acids. Between pH 8.4 and pH 7.4 Delta H* decreases from 15 to 12 kcal/mol, while Delta S* decreases from -18 to -26 eu for 2 (R = Me or Pr), consistent with concerted proton transfer in the dehydration transition state. Surprisingly, the rate also increases in more alkaline conditions up to 12-fold (in zero buffer), coincident with formation of a pteridine anion (pK = 9.8). Below pH 11.5 catalysis by buffer base was also observed. A solvent kinetic isotope effect (k(H2O)/k(D2O)) of 2.6, 2.2, and 3.5 was found in dilute buffers at pH 7.4, 8.2, and 10.9, respectively. The overall rate of disappearance of 2 (R = dihydroxypropyl) is similar to that of the alkyl analogs, but a second pathway competes with dehydration to produce a compound tentatively identified as a side-chain 4a-cyclic adduct, which subsequently decays to quinoid 6(R)-dihydrobiopterin. These synthetic substrates have permitted the first kinetic characterization of 4a-hydroxytetrahydropterin dehydratase (Rebrin, I.; et al. Biochemistry 1995, 34, 5801-5810), the enzyme involved in cofactor regeneration during aromatic amino acid hydroxylation.

  DOI：

  10.1021/ja00146a005