5-amino-6-[[(4R,5R)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]methylsulfanyl]-1H-pyrimidine-2,4-dione | 952288-36-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-amino-6-[[(4R,5R)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]methylsulfanyl]-1H-pyrimidine-2,4-dione
• CAS: 952288-36-7
• 化学式: C₁₅H₂₃N₃O₆S
• 分子量: 373.43
• InChiKey: DFUNVKNGRNNBEF-KHQFGBGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-amino-6-[[(4R,5R)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]methylsulfanyl]-1H-pyrimidine-2,4-dione 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以64%的产率得到2,4-Dioxo-6-[[(2r,3r,4r)-2,3,4,5-tetrahydroxypentyl]sulfanyl]-1,2,3,4-tetrahydropyrimidin-5-aminium chloride
  参考文献：
  名称：

  Synthesis and Enzyme Inhibitory Activity of the S-Nucleoside Analogue of the Ribitylaminopyrimidine Substrate of Lumazine Synthase and Product of Riboflavin Synthase

  摘要：

  [GRAPHICS]Lumazine synthase and riboflavin synthase catalyze the last two steps in the biosynthesis of riboflavin. To obtain structural and mechanistic probes of these two enzymes, as well as inhibitors of potential value as antibiotics, a sulfur analogue of the pyrimidine substrate of the lumazine synthase-catalyzed reaction and product of the riboflavin synthase-catalyzed reaction was designed. Facile syntheses of the S-nucleoside 5-amino-6-(D-ribitylthio)pyrimidine-2,4(1H,3H)-dione hydrochloride (15) and its nitro precursor 5-nitro-6-(D-ribitylthio)pyrimidine-2,4(I H,3H)-dione (14) are described. These compounds were tested against lumazine synthase and riboflavin synthase obtained from a variety of microorganisms. Compounds 14 and 15 were found to be inhibitors of both riboflavin synthase and lumazine synthase. Compound 14 is an inhibitor of Bacillus subtilis lumazine synthase (K-i 26 mu M), Schizosaccharomyces pombe lumazine synthase (K-i 2.0 mu M), Mycobacterium tuberculosis lumazine synthase (K-i 11 mu M), Escherichia coli riboflavin synthase (K-i 2.7 mu M), and Mycobacterium tuberculosis riboflavin synthase (K-i 0.56 mu M), while compound 15 is an inhibitor of B. subtilis lumazine synthase (K-i 2.6 mu M), S. pombe lumazine synthase (K-i 0.16 mu M), M. tuberculosis lumazine synthase (K-i 31 mu M), E. coli riboflavin synthase (K-i 47 mu M), and M. tuberculosis riboflavin synthase (K-i 2.5 mu M).

  DOI：

  10.1021/jo0709495
• 作为产物：
  描述：

  ((4S,4’R,5S)-2,2,2’,2’-tetramethyl-[4,4’-bi(1,3-dioxolan)]-5-yl)methanol 在 吡啶 、 4-二甲氨基吡啶 、 sodium disulfite 、 sodium methylate 、 碳酸氢钠 、 sodium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 50.0h， 生成 5-amino-6-[[(4R,5R)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]methylsulfanyl]-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Enzyme Inhibitory Activity of the S-Nucleoside Analogue of the Ribitylaminopyrimidine Substrate of Lumazine Synthase and Product of Riboflavin Synthase

  摘要：

  [GRAPHICS]Lumazine synthase and riboflavin synthase catalyze the last two steps in the biosynthesis of riboflavin. To obtain structural and mechanistic probes of these two enzymes, as well as inhibitors of potential value as antibiotics, a sulfur analogue of the pyrimidine substrate of the lumazine synthase-catalyzed reaction and product of the riboflavin synthase-catalyzed reaction was designed. Facile syntheses of the S-nucleoside 5-amino-6-(D-ribitylthio)pyrimidine-2,4(1H,3H)-dione hydrochloride (15) and its nitro precursor 5-nitro-6-(D-ribitylthio)pyrimidine-2,4(I H,3H)-dione (14) are described. These compounds were tested against lumazine synthase and riboflavin synthase obtained from a variety of microorganisms. Compounds 14 and 15 were found to be inhibitors of both riboflavin synthase and lumazine synthase. Compound 14 is an inhibitor of Bacillus subtilis lumazine synthase (K-i 26 mu M), Schizosaccharomyces pombe lumazine synthase (K-i 2.0 mu M), Mycobacterium tuberculosis lumazine synthase (K-i 11 mu M), Escherichia coli riboflavin synthase (K-i 2.7 mu M), and Mycobacterium tuberculosis riboflavin synthase (K-i 0.56 mu M), while compound 15 is an inhibitor of B. subtilis lumazine synthase (K-i 2.6 mu M), S. pombe lumazine synthase (K-i 0.16 mu M), M. tuberculosis lumazine synthase (K-i 31 mu M), E. coli riboflavin synthase (K-i 47 mu M), and M. tuberculosis riboflavin synthase (K-i 2.5 mu M).

  DOI：

  10.1021/jo0709495

文献信息

• <i>O</i>-Nucleoside, <i>S</i>-Nucleoside, and <i>N</i>-Nucleoside Probes of Lumazine Synthase and Riboflavin Synthase
  作者：Arindam Talukdar、Yujie Zhao、Wei Lv、Adelbert Bacher、Boris Illarionov、Markus Fischer、Mark Cushman

  DOI：10.1021/jo3010364

  日期：2012.7.20

  nitro groups, alkenes, and halogens. The target compounds were tested as inhibitors of lumazine synthase and riboflavin synthase obtained from a variety of microorganisms. In general, the S-nucleosides and N-nucleosides were more potent than the corresponding O-nucleosides as lumazine synthase and riboflavin synthase inhibitors, while the C-nucleosides were the least potent. A series of molecular dynamics

  Lumazine 合酶催化核黄素生物合成的倒数第二步，而核黄素合酶催化最后一步。O-核苷、S-核苷和N已经合成了假设的 lumazine 生物合成中间体的核苷类似物，以获得这两种酶的结构和机制探针，以及作为抗生素具有潜在价值的抑制剂。设计了在其他容易还原的官能团存在下通过在 Lindlar 催化剂上受控氢解来选择性裂解苄基保护基团的方法。脱保护反应在其他反应性官能团（包括硝基、烯烃和卤素）的存在下进行。目标化合物作为从各种微生物获得的 lumazine 合酶和核黄素合酶的抑制剂进行了测试。一般来说，S-核苷和N-核苷比相应的O-核苷更有效核苷作为 lumazine 合酶和核黄素合酶抑制剂，而C-核苷的效力最低。进行了一系列分子动力学模拟，然后使用泊松-玻尔兹曼/表面积 (MM-PBSA) 方法进行自由能计算，以使配体与 lumazine 合酶结合的结果合理化，结果提供了对配体结合以及稳定酶催化反应中的中间体的分子力。
• Synthesis and Enzyme Inhibitory Activity of the <i>S</i>-Nucleoside Analogue of the Ribitylaminopyrimidine Substrate of Lumazine Synthase and Product of Riboflavin Synthase
  作者：Arindam Talukdar、Boris Illarionov、Adelbert Bacher、Markus Fischer、Mark Cushman

  DOI：10.1021/jo0709495

  日期：2007.9.1

  [GRAPHICS]Lumazine synthase and riboflavin synthase catalyze the last two steps in the biosynthesis of riboflavin. To obtain structural and mechanistic probes of these two enzymes, as well as inhibitors of potential value as antibiotics, a sulfur analogue of the pyrimidine substrate of the lumazine synthase-catalyzed reaction and product of the riboflavin synthase-catalyzed reaction was designed. Facile syntheses of the S-nucleoside 5-amino-6-(D-ribitylthio)pyrimidine-2,4(1H,3H)-dione hydrochloride (15) and its nitro precursor 5-nitro-6-(D-ribitylthio)pyrimidine-2,4(I H,3H)-dione (14) are described. These compounds were tested against lumazine synthase and riboflavin synthase obtained from a variety of microorganisms. Compounds 14 and 15 were found to be inhibitors of both riboflavin synthase and lumazine synthase. Compound 14 is an inhibitor of Bacillus subtilis lumazine synthase (K-i 26 mu M), Schizosaccharomyces pombe lumazine synthase (K-i 2.0 mu M), Mycobacterium tuberculosis lumazine synthase (K-i 11 mu M), Escherichia coli riboflavin synthase (K-i 2.7 mu M), and Mycobacterium tuberculosis riboflavin synthase (K-i 0.56 mu M), while compound 15 is an inhibitor of B. subtilis lumazine synthase (K-i 2.6 mu M), S. pombe lumazine synthase (K-i 0.16 mu M), M. tuberculosis lumazine synthase (K-i 31 mu M), E. coli riboflavin synthase (K-i 47 mu M), and M. tuberculosis riboflavin synthase (K-i 2.5 mu M).