[(2R)-2-羟基-3-氧代丁基]磷酸二氢酯 | 130971-02-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 中文名称: [(2R)-2-羟基-3-氧代丁基]磷酸二氢酯
• 英文名称: L-3,4-dihydroxy-2-butanone 4-phosphate
• 英文别名: (3S)-3,4-dihydroxy-2-butanone 4-phosphate；3,4-dihydroxybutanone 4-phosphate；L-3,4-dihydroxy-2-butanone phosphate；3,4-dihydroxy-2-butanone 4-phosphate；3,4-Dihydroxy-2-butanone-4-phosphate；[(2S)-2-hydroxy-3-oxobutyl] dihydrogen phosphate
• CAS: 130971-02-7
• 化学式: C₄H₉O₆P
• 分子量: 184.086
• InChiKey: OKYHYXLCTGGOLM-BYPYZUCNSA-N

物化性质

• 沸点：
  425.2±55.0 °C(Predicted)
• 密度：
  1.599±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6,7-二甲基核糖基2,4-二羟基蝶啶 、 [(2R)-2-羟基-3-氧代丁基]磷酸二氢酯 在 riboflavin synthase 、 sodium chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 生成 维生素 B2
  参考文献：
  名称：

  Lumazine 合酶和核黄素合酶的 O-核苷、S-核苷和 N-核苷探针

  摘要：

  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。

  DOI：

  10.1021/jo3010364
• 作为产物：
  描述：

  Ribulose-5-phosphate 生成 [(2R)-2-羟基-3-氧代丁基]磷酸二氢酯
  参考文献：
  名称：

  VOLK, RAINER, FAK. CHEM., BIOL. UND GEOWISS. TESNN. UNIV. MUNSNEN, DOKT. NATURWISS. S19+

  摘要：

  DOI：

文献信息

• A New Series of 3-Alkyl Phosphate Derivatives of 4,5,6,7-Tetrahydro-1-<scp>d</scp>-ribityl-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidinedione as Inhibitors of Lumazine Synthase:  Design, Synthesis, and Evaluation
  作者：Yanlei Zhang、Guangyi Jin、Boris Illarionov、Adelbert Bacher、Markus Fischer、Mark Cushman

  DOI：10.1021/jo070982r

  日期：2007.9.1

  hypothetical intermediate in the lumazine synthase-catalyzed reaction were synthesized and evaluated as lumazine synthase inhibitors. The key steps of the synthesis were C-5 deprotonation of 4-chloro-2,6-dimethoxypyrimidine, acylation of the resulting anion, and conversion of the product to a pyrazolopyrimidine with hydrazine. Alkylation of the pyrazolopyrimidine with a substituted ribityl iodide and

  Lumazine合酶催化核黄素生物合成中的倒数第二个步骤。合成了在LUM嗪合酶催化的反应中的假定中间体的三个系列的吡唑并嘧啶类似物的同源系列，并评价为LUM嗪合酶抑制剂。合成的关键步骤是4-氯-2,6-二甲氧基嘧啶的C-5脱质子化，所得阴离子的酰化作用以及产物与肼的转化为吡唑并嘧啶。吡唑并嘧啶与取代的碘化碘化物的烷基化和核糖链的脱保护得到了最终的三种产物。这三种化合物都是结核分枝杆菌，稻瘟病菌，白色念珠菌的鲁嗪合酶的极强抑制剂。，和粟酒裂殖酵母（Schizosaccharomyces pombe lumazine）合酶，其抑制常数在低纳摩尔至亚纳摩尔范围内。结合至结核分枝杆菌lumazine合酶的同系物之一的分子模型表明，lumazine合酶催化的反应途径中的假设中间体与代谢稳定的类似物均相似地结合。
• Biosynthesis of Riboflavin. The Reaction Catalyzed by 6,7-Dimethyl-8-ribityllumazine Synthase Can Proceed without Enzymatic Catalysis under Physiological Conditions^†
  作者：Klaus Kis、Karl Kugelbrey、Adelbert Bacher

  DOI：10.1021/jo001120s

  日期：2001.4.1

  lumazine by condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and 3,4-dihydroxy-2-butanone 4-phosphate is catalyzed by the enzyme, lumazine synthase. We show that the condensation reaction can proceed without enzyme catalysis in dilute aqueous solution at room temperature and neutral pH. The reaction rate is proportional to e (pH). The activation energy of the uncatalyzed reaction is E(a)

  6,7-二甲基-8-ribityllumazine是维生素核黄素的生物合成前体。通过5-氨基-6-核糖基氨基-2,4（1H，3H）-嘧啶二酮和3,4-二羟基-2-丁酮4-磷酸的缩合反应，通过生物合成酶催化合成玉米素。我们表明在室温和中性pH的稀水溶液中，缩合反应可以在没有酶催化的情况下进行。反应速率与e（pH）成正比。未催化反应的活化能为E（a）= 46.3 kJ mol（-）（1）。未催化反应的区域选择性随pH和温度（65℃和pH 7.75的70％）而增加。数据表明未催化反应通过两个不同的反应途径分配。
• Evidence for the Chemical Mechanism of RibB (3,4-Dihydroxy-2-butanone 4-phosphate Synthase) of Riboflavin Biosynthesis
  作者：Nikola Kenjić、Kathleen M. Meneely、Daniel J. Wherritt、Melissa C. Denler、Timothy A. Jackson、Graham R. Moran、Audrey L. Lamb

  DOI：10.1021/jacs.2c03376

  日期：2022.7.20

  4-phosphate synthase) is a magnesium-dependent enzyme that excises the C4 of d-ribulose-5-phosphate (d-Ru5P) as formate. RibB generates the four-carbon substrate for lumazine synthase that is incorporated into the xylene moiety of lumazine and ultimately the riboflavin isoalloxazine. The reaction was first identified by Bacher and co-workers in the 1990s, and their chemical mechanism hypothesis became

  RibB (3,4-dihydroxy-2-butanone 4-phosphate synthase) 是一种镁依赖性酶，可切除d-核酮糖-5-磷酸 ( d-Ru5P) 作为甲酸盐。RibB 为 lumazine 合酶生成四碳底物，该底物被并入 lumazine 的二甲苯部分，最终形成核黄素异恶嗪。Bacher 及其同事在 1990 年代首次发现了该反应，尽管直接证据很少，但他们的化学机制假设成为规范。RibB 的 X 射线晶体结构通常在存在非天然金属和/或配体非底物类似物的情况下溶解时显示两个金属离子，并且共识假设机制已纳入该辅因子组。我们使用了多种生化方法来进一步表征来自霍乱弧菌的 RibB 催化的化学性质(VcRibB)。我们表明在金属离子浓度等​​于酶浓度时实现了完全活性。这通过用锰和与Mn 2+和多种糖磷酸盐配体的晶体结构重构的酶的电子顺磁共振得到证实。使用单周转反应的酸猝灭结合
• Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase
  作者：Arindam Talukdar、Ekaterina Morgunova、Jianxin Duan、Winfried Meining、Nicolas Foloppe、Lennart Nilsson、Adelbert Bacher、Boris Illarionov、Markus Fischer、Rudolf Ladenstein、Mark Cushman

  DOI：10.1016/j.bmc.2010.03.072

  日期：2010.5

  Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid ( 9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a K-i of 70 mu M. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (K-i 38 mu M). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve pi-pi stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87. (C) 2010 Elsevier Ltd. All rights reserved.
• Incorporation of an Amide into 5-Phosphonoalkyl-6-<scp>d</scp>-ribitylaminopyrimidinedione Lumazine Synthase Inhibitors Results in an Unexpected Reversal of Selectivity for Riboflavin Synthase vs Lumazine Synthase
  作者：Mark Cushman、Donglai Yang、Jeffrey T. Mihalic、Jinhua Chen、Stefan Gerhardt、Robert Huber、Markus Fischer、Klaus Kis、Adelbert Bacher

  DOI：10.1021/jo020144r

  日期：2002.10.1

  Several analogues of a hypothetical intermediate in the reaction catalyzed by lumazine synthase were synthesized and tested as inhibitors of both Bacillus subtilis lumazine synthase and Escherichia coli riboflavin synthase. The new compounds were designed by replacement of a two-carbon fragment of several 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors with an amide linkage that was envisioned as an analogue of a Schiff base moiety of a hypothetical intermediate in the enzyme-catalyzed reaction. The incorporation of the amide group led to an unexpected reversal in selectivity for inhibition of lumazine synthase vs riboflavin synthase. Whereas the parent 5-phosphonoalkyl-6-D-ribitylaminopyrimidinediones were lumazine synthase inhibitors and did not inhibit riboflavin synthase, the amide-containing derivatives inhibited riboflavin synthase and were only very weak or inactive as lumazine synthase inhibitors. Molecular modeling of inhibitor-lumazine synthase complexes did not reveal a structural basis for these unexpected findings. However, molecular modeling of one of the inhibitors with E. coli riboflavin synthase demonstrated that the active site of the enzyme could readily accommodate two ligand molecules.