5-amino-6-D-ribitol-1-ylamino-1H-pyrimidine-2,4-dione; hydrochloride | 134452-11-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-amino-6-D-ribitol-1-ylamino-1H-pyrimidine-2,4-dione; hydrochloride
• 英文别名: 5-Amino-6-D-ribit-1-ylamino-1H-pyrimidin-2,4-dion; Hydrochlorid；5-A-RU hydrochloride；5-amino-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidine-2,4-dione;hydrochloride
• CAS: 134452-11-2
• 化学式: C₉H₁₆N₄O₆*ClH
• 分子量: 312.71
• InChiKey: VGAFXPBLNINPEY-ZUOBHZEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.57
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  179
• 氢给体数：
  8
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-amino-6-D-ribitol-1-ylamino-1H-pyrimidine-2,4-dione; hydrochloride 在 sodium sulfite 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 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：

  卡培他滨杂质25 在 ammonium hydroxide 、 sodium dithionite 、 ammonium acetate 、 sodium cyanoborohydride 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 26.0h， 生成 5-amino-6-D-ribitol-1-ylamino-1H-pyrimidine-2,4-dione; hydrochloride
  参考文献：
  名称：

  MR1配体糖类似物对粘膜相关不变T（MAIT）细胞活化的影响。

  摘要：

  粘膜相关不变T（MAIT）细胞是最近鉴定的先天样T淋巴细胞的一个子集，它们似乎在从病毒和细菌感染到自身免疫性疾病和癌症的许多病理中起着重要作用。MAIT细胞通过MR1在MAIT T细胞受体（TCR）的抗原呈递细胞上呈递配体而被激活，但是很少有研究探索系统改变配体结构对MR1结合和MAIT细胞活化的影响。在此，我们报道了关于已知MAIT细胞激动剂7-羟基-6-甲基-8-d-ribityllumazine（RL-6-Me-7-OH）和5中糖基序变化的影响的首次研究。 （2-氧代丙基亚氨基）-6-d-核糖基氨基尿嘧啶（5-OP-RU）。MAIT细胞的四聚体染色显示缺少2' lumazines的糖主链上的-羟基基团改善了MR1-MAIT TCR结合，这可以使用计算对接研究进行合理化。尽管没有一种二嗪类化合物激活MAIT细胞，但所有5-OP-RU类似物均显示出显着的MAIT细胞激活，其中几种类似物的

  DOI：

  10.1039/c9ob01436e

文献信息

• Agonistic or antagonistic mucosal-associated invariant T (MAIT) cell activity is determined by the 6-alkylamino substituent on uracil MR1 ligands
  作者：Chriselle D. Braganza、Chihiro Motozono、Koh-Hei Sonoda、Sho Yamasaki、Kensuke Shibata、Mattie S. M. Timmer、Bridget L. Stocker

  DOI：10.1039/d0cc00247j

  日期：——

  The 6-alkylamino side chain of aminouracil MR1 ligands controls MAIT cell agonistic or antagonistic activity.

  6-烷基氨基尿嘧啶MR1配体的侧链控制MAIT细胞的激动或拮抗活性。
• Synthesis, stabilization, and characterization of the MR1 ligand precursor 5-amino-6-D-ribitylaminouracil (5-A-RU)
  作者：Kelin Li、Charles K. Vorkas、Ashutosh Chaudhry、Donielle L. Bell、Richard A. Willis、Alexander Rudensky、John D. Altman、Michael S. Glickman、Jeffrey Aubé

  DOI：10.1371/journal.pone.0191837

  日期：——

  Mucosal-associated invariant T (MAIT) cells are an abundant class of innate T cells restricted by the MHC I-related molecule MR1. MAIT cells can recognize bacterially-derived metabolic intermediates from the riboflavin pathway presented by MR1 and are postulated to play a role in innate antibacterial immunity through production of cytokines and direct bacterial killing. MR1 tetramers, typically stabilized by the adduct of 5-amino-6-D-ribitylaminouracil (5-A-RU) and methylglyoxal (MeG), are important tools for the study of MAIT cells. A long-standing problem with 5-A-RU is that it is unstable upon storage. Herein we report an efficient synthetic approach to the HCl salt of this ligand, which has improved stability during storage. We also show that synthetic 5-A-RU•HCl produced by this method may be used in protocols for the stimulation of human MAIT cells and production of both human and mouse MR1 tetramers for MAIT cell identification.

  粘膜相关不变 T (MAIT) 细胞是一类丰富的先天 T 细胞，受 MHC I 相关分子 MR1 的限制。 MAIT 细胞可以识别 MR1 呈现的核黄素途径中细菌衍生的代谢中间体，并被认为通过产生细胞因子和直接杀灭细菌，在先天抗菌免疫中发挥作用。 MR1 四聚体通常由 5-氨基-6-D-核糖氨基尿嘧啶 (5-A-RU) 和甲基乙二醛 (MeG) 的加合物稳定，是研究 MAIT 细胞的重要工具。 5-A-RU 的一个长期存在的问题是它在存储时不稳定。在此，我们报告了一种该配体 HCl 盐的有效合成方法，该方法提高了储存期间的稳定性。我们还表明，通过这种方法产生的合成 5-A-RU·HCl 可用于刺激人类 MAIT 细胞以及生产人类和小鼠 MR1 四聚体以进行 MAIT 细胞鉴定的方案。
• Synthesis of epimeric 6,7-bis(trifluoromethyl)-8-ribityllumazine hydrates. Stereoselective interaction with the light riboflavin synthase of Bacillus subtilis
  作者：Mark Cushman、Donald A. Patrick、Adelbert Bacher、Johannes Scheuring

  DOI：10.1021/jo00015a009

  日期：1991.7

  Reaction of perfluorobutane-2,3-dione with 5-amino-6-(D-ribitylamino)pyrimidine-2,4(1H,3H)-dione hydrochloride (13) gave a mixture of the epimeric covalently hydrated fluorolumazines 14a and 14b, which were separated by preparative HPLC. The epimer that eluted first using a methanol-ammonium formate buffer mobile phase (epimer A) interacts stereospecifically with light riboflavin synthase of Bacillus subtilis as shown by F-19 NMR spectroscopy, which provided evidence for the formation of three enzyme-bound species that exchange with the free ligand on the NMR time scale. Dissociation constants of 13.0 and 16.2-mu-M were obtained from NMR and equilibrium dialysis experiments, respectively. Both methods showed the binding of one ligand molecule per protein subunit. Epimer A is a competitive inhibitor of the enzyme (K(I) = 38-mu-M at pH 6.8). Epimer B did not bind to the enzyme.
• Masuda et al., Chemical and pharmaceutical bulletin, 1959, vol. 7, p. 366
  作者：Masuda et al.

  DOI：——

  日期：——
• Synthesis of 2,6-Dioxo-(1 H ,3 H )-9- N -ribitylpurine and 2,6-Dioxo-(1 H ,3 H )-8-aza-9- N -ribitylpurine as inhibitors of lumazine synthase and riboflavin synthase
  作者：Mark Cushman、Farahnaz Mavandadi、Karl Kugelbrey、Adelbert Bacher

  DOI：10.1016/s0968-0896(98)00013-3

  日期：1998.4

  2,6-Dioxo-(1H,3H)-9-N-ribitylpurine (6) and 2,6-dioxo-(1H,3H)-8-aza-9-N-ribitylpurin (7) have been synthesized and evaluated as inhibitors of lumazine synthase and riboflavin synthase. Reaction of 5-amino-6-ribityl-aminouracil hydrochloride (8) with diethoxymethyl acetate (9) afforded the purine 6, while diazotization of 8 afforded the 8-aza purine 7. Compounds 6 and 7 were evaluated against lumazine synthase of Bacillus subtilis and riboflavin synthase of Escherichia coli. Both 6 and 7 were better inhibitors of lumazine synthase than riboflavin synthase. The 8-azapurine 7 had a lower K-I (0.33 and 0.39 mM) than the purine 6 (0.47 and 0.54 mM) when evaluated with lumazine synthase and riboflavin synthase, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.