6-(trifluoromethyl)-8-(D-ribityl)lumazine

• 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: 6-(trifluoromethyl)-8-(D-ribityl)lumazine
• 英文别名: 8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-6-(trifluoromethyl)pteridine-2,4-dione
• 化学式: C₁₂H₁₃F₃N₄O₆
• 分子量: 366.254
• InChiKey: MGTUBLUQHAIEJW-UUEMRFSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-(trifluoromethyl)-8-(D-ribityl)lumazine 在 sodium sulfide 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Fluorine-19 NMR studies of the mechanism of riboflavin synthase. Synthesis of 6-(trifluoromethyl)-8-(D-ribityl)lumazine and derivatives

  摘要：

  6-(Trifluoromethyl)-8-(D-ribityl)lumazine (17) was synthesized in order to study its reactivity at C-7 and its binding to riboflavin synthase of Bacillus subtilis. Compound 17 was prepared by reaction of 5-amino-4-[(D-ribityl)amino]-2,4-(1H,3H)-pyrimidinedione hydrochloride (3.HCl) with trifluoropyruvaldehyde hydrate (18). NMR studies revealed that under basic conditions, 17 forms only one major anionic species in which the oxygen of the 3'-hydroxyl group on the ribityl side chain binds covalently to C-7 of the lumazine, resulting in the formation of a pyran ring. As a model for possible addition of nucleophilic groups on the enzyme to C-7 of 17, the reactions of 17 with a variety of sulfur nucleophiles were studied. Fluorolumazine 17 was found to form covalent adducts 27-31 with sulfite, sulfide, mercaptoethanol, D,L-1,4-dithiothreitol, and L-cysteine. Three molecules of 17 were found to bind per enzyme molecule (alpha subunit trimer). Equilibrium dialysis experiments and F-19 NMR spectroscopy provided dissociation constants K(D) of 38 and 100 muM, respectively. The inhibition constant K(I) was 58 muM. There was no evidence obtained for the formation of a covalent adduct between the fluorolumazine 17 and the enzyme, suggesting that the nucleophile adding to C-7 during the enzyme-catalyzed reaction is derived from water. The covalent adducts obtained from 17 were found to bind to the enzyme significantly more tightly than 17 itself. The covalent adducts 27-31 as well as 17 could be displaced from the enzyme by both riboflavin (2) and 5-nitroso-6-[(D-ribityl)-amino]-2,4(1H,3H)-pyrimidinedione (32).

  DOI：

  10.1021/jo00067a041
• 作为产物：
  描述：

  5-amino-6-D-ribitol-1-ylamino-1H-pyrimidine-2,4-dione; hydrochloride 、 trifluoropyruvaldehyde hydrate 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以27 mg的产率得到6-(trifluoromethyl)-8-(D-ribityl)lumazine
  参考文献：
  名称：

  Fluorine-19 NMR studies of the mechanism of riboflavin synthase. Synthesis of 6-(trifluoromethyl)-8-(D-ribityl)lumazine and derivatives

  摘要：

  6-(Trifluoromethyl)-8-(D-ribityl)lumazine (17) was synthesized in order to study its reactivity at C-7 and its binding to riboflavin synthase of Bacillus subtilis. Compound 17 was prepared by reaction of 5-amino-4-[(D-ribityl)amino]-2,4-(1H,3H)-pyrimidinedione hydrochloride (3.HCl) with trifluoropyruvaldehyde hydrate (18). NMR studies revealed that under basic conditions, 17 forms only one major anionic species in which the oxygen of the 3'-hydroxyl group on the ribityl side chain binds covalently to C-7 of the lumazine, resulting in the formation of a pyran ring. As a model for possible addition of nucleophilic groups on the enzyme to C-7 of 17, the reactions of 17 with a variety of sulfur nucleophiles were studied. Fluorolumazine 17 was found to form covalent adducts 27-31 with sulfite, sulfide, mercaptoethanol, D,L-1,4-dithiothreitol, and L-cysteine. Three molecules of 17 were found to bind per enzyme molecule (alpha subunit trimer). Equilibrium dialysis experiments and F-19 NMR spectroscopy provided dissociation constants K(D) of 38 and 100 muM, respectively. The inhibition constant K(I) was 58 muM. There was no evidence obtained for the formation of a covalent adduct between the fluorolumazine 17 and the enzyme, suggesting that the nucleophile adding to C-7 during the enzyme-catalyzed reaction is derived from water. The covalent adducts obtained from 17 were found to bind to the enzyme significantly more tightly than 17 itself. The covalent adducts 27-31 as well as 17 could be displaced from the enzyme by both riboflavin (2) and 5-nitroso-6-[(D-ribityl)-amino]-2,4(1H,3H)-pyrimidinedione (32).

  DOI：

  10.1021/jo00067a041