TDP | 15252-08-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: TDP
• 英文别名: Ribosylthymidine diphosphate；[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate
• CAS: 15252-08-1
• 化学式: C₁₀H₁₆N₂O₁₂P₂
• 分子量: 418.191
• InChiKey: CYDYNVMCEGXBEM-JXOAFFINSA-N

物化性质

• 密度：
  1.902±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  212
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  海藻糖 、 TDP 在 Pyrococcus horikoshii trehalose synthase 作用下， 反应 24.0h， 生成 UDP-Glc
  参考文献：
  名称：

  Catalytic reversibility of Pyrococcus horikoshii trehalose synthase: Efficient synthesis of several nucleoside diphosphate glucoses with enzyme recycling

  摘要：

  The trehalose synthase (TreT) from Pyrococcus horikoshii represented reversible catalysis in alternative synthesis of trehalose and nucleoside 5'-diphosphate-glucose (NDP-Glc), depending on the substrates involved. TreT from P. horikoshii had differential preferences on NDP-Glc as a donor for trehalose synthesis, in which guanosine 5'-diphosphate (GDP)-Glc was the most favored in terms of reaction specificity, k(cat)/K-m. Uridine 5'-diphosphate (UDP)- and adenosine 5'-diphosphate (ADP)-Glcs were employed with less preferences. This enzyme reversely cleaved trehalose to transfer the glucosyl moiety to various NDPs, efficiently producing NDP-Glcs. Although ADP-Glc was the least favorable donor, the counterpart, ADP, was the most favorable acceptor for the reverse synthesis of NDP-Glc in k(cat)/K-m. GDP and UDP were less preferred, compared to ADP. In a batch reaction of 12 h, the molar yield of NDP-Glc per NDP used was decreased approximately in the order of ADP-Glc > GDP-Glc > cytidine 5'-diphosphate (CDP)-Glc or UDP-Glc. The overall productivity of the enzyme was largely improved in a gram scale for NDP-Glcs using repetitive batch reactions with enzyme recycling. Thus, it is suggested that TreT from P. horikoshii may be useful for the regeneration of NDP-Glc from NDP, especially for ADP-Glc from ADP, with trehalose as a glucose resource. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.procbio.2010.07.030
• 作为产物：
  描述：

  5-甲基尿甙 在 三氯氧磷 、 三辛胺 、 磷酸 作用下， 以61 %的产率得到TDP
  参考文献：
  名称：

  一锅法合成核苷二磷酸

  摘要：

  本发明提供一锅法合成核苷二磷酸的方法，其中，包括：1)向核苷的磷酸三乙酯溶液中加入三氯氧磷反应；2)将磷酸、三辛胺与磷酸三乙酯的混合溶液加入1)的反应液中；其中，核苷、磷酸、三辛胺的摩尔比为1：(8～20)：(8～20)，磷酸三乙酯作为溶剂使用。本发明方法步骤简单，一锅法即可完成二磷酸的形成，成本低，绿色环保，节能低耗，具有较高的产业化应用前景。

  公开号：

  CN117362369A
• 作为试剂：
  描述：

  正戊醛 在 DL-dithiothreitol 、 3-hydroxypropionaldehyde dehydrogenase 、 β-烟酰胺腺嘌呤二核苷酸 、 TDP 作用下， 以 aq. buffer 为溶剂， 生成 正戊酸
  参考文献：
  名称：

  Production of C5 carboxylic acids in engineered Escherichia coli

  摘要：

  Valeric acid and 2-methylbutyric acid serve as chemical intermediates for a variety of applications such as plasticizers, lubricants and pharmaceuticals. The commercial process for their production uses toxic intermediates like synthesis gas and relies on non-renewable petroleum-based feedstock. In this work, synthetic metabolic pathways were constructed in Escherichia coli for the renewable production of these chemicals directly from glucose. The native leucine and isoleucine biosynthetic pathways in E. calf were expanded for the synthesis of valeric acid and 2-methylbutyric acid (2MB) respectively by the introduction of aldehyde dehydrogenases and 2-ketoacid decarboxylases. Various aldehyde dehydrogenases and 2-ketoacid decarboxylases were investigated for their activities in the constructed pathways. Highest titers of 2.59 g/L for 2-mthylbutyric acid and 2.58 g/L for valeric acid were achieved in shake flask experiments through optimal combinations of these enzymes. This work demonstrates the feasibility of renewable production of these high volume aliphatic carboxylic acids. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.procbio.2012.07.005

文献信息

• Engineering Human Fhit, a Diadenosine Triphosphate Hydrolase, into an Efficient Dinucleoside Polyphosphate Synthase
  作者：Kaisheng Huang、Perry A. Frey

  DOI：10.1021/ja0400640

  日期：2004.8.1

  dinucleoside polyphosphates. Fhit catalyzes the Mg2+-dependent hydrolysis of P1-5'-O-adenosine-P3-5'-O-adenosine triphosphate (Ap3A) to AMP and MgADP. Mutation of His96 to glycine disables Fhit as a catalyst for the hydrolysis of phosphoanhydrides such as Ap3A. However, the mutated enzyme H96G-Fhit efficiently catalyzes the synthesis of phosphoanhydride bonds in reactions of nucleoside-5'-phosphimidazolides

  假定的人类肿瘤抑制基因 FHIT 编码 Fhit，即脆弱的组氨酸三联体蛋白。Fhit 被认为参与涉及双核苷多磷酸的信号转导途径。Fhit 催化 P1-5'-O-腺苷-P3-5'-O-三磷酸腺苷 (Ap3A) 依赖 Mg2+ 水解为 AMP 和 MgADP。His96 突变为甘氨酸会使 Fhit 作为磷酸酐（如 Ap3A）水解的催化剂失效。然而，突变酶 H96G-Fhit 在核苷 5'-磷咪唑化物与核苷二磷酸和三磷酸的反应中有效催化磷酸酐键的合成。H96G-Fhit 可用于合成多种二核苷三磷酸和四磷酸。我们在此描述了使用 H96G-Fhit 催化 Ap3A、Ap3C、Ap3G、Ap3T、Ap3U、Cp3U、Tp3U、dAp3U、Ap4A、
• Method of treating lung diseases with uridine 5'-diphosphate and analogs
  申请人：The University of North Carolina at Chapel Hill

  公开号：US06022527A1

  公开（公告）日：2000-02-08

  Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ; X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H; R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

  化合物I的公式：##STR1## 其中：X.sub.1和X.sub.2分别独立地为O.sup.-或S.sup.-; X.sub.3和X.sub.4分别独立地为--H或--OH，但X.sub.3和X.sub.4不能同时为--H; R.sub.1选自包括O、亚胺基、亚甲基和二卤甲基的基团; R.sub.2选自包括H、卤素、烷基、取代烷基、烷氧基、硝基和叠氮基的基团; R.sub.3选自包括H、烷基、酰基、芳基和芳基烷基的基团; R.sub.4选自包括--OR'、--SR'、--NR'和--NR'R"的基团，其中R'和R"独立地选自包括H、烷基、取代烷基、芳基、取代芳基、芳基烷基、烷氧基和芳氧基的基团，但当R.sub.4从嘧啶环的4位碳原子上的氧或硫原子双键时，R'不存在。这些化合物可用于水合肺黏液分泌物和治疗肺部疾病，例如囊性纤维化、呼吸机相关性肺炎、慢性支气管炎、慢性阻塞性肺疾病和原发性纤毛运动障碍。还描述了含有化合物I的药物组合物和新的化合物I。
• Method of treating lung diseases with uridine 5′-diphosphate and analogs thereof
  申请人：The University of North Carolina at Chapel Hill

  公开号：US06451288B1

  公开（公告）日：2002-09-17

  Compounds of Formula I: wherein: X1, and X2 are each independently either O− or S−; X3 and X4 are each independently either —H or —OH, with the proviso that X3 and X4 are not simultaneously —H; R1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R4 is selected from the group consisting of —OR′, —SR′, —NR′, and —NR′R″, wherein R′ and R″ are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R′ is absent when R4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

  式I的化合物：其中：X1和X2各自独立地为O−或S−；X3和X4各自独立地为—H或—OH，但X3和X4不能同时为—H；R1从O，亚胺基，亚甲基和二卤甲基的群中选择；R2从H，卤素，烷基，取代烷基，烷氧基，硝基和叠氮基的群中选择；R3从H，烷基，酰基，芳基和芳基烷基的群中选择；R4从—OR′，—SR′，—NR′和—NR′R″的群中选择，其中R′和R″各自独立地从H，烷基，取代烷基，芳基，取代芳基，芳基烷基，烷氧基和芳氧基的群中选择，但当R4从嘧啶环的4位碳原子上的氧或硫原子与碳双键时，R′不出现。这些化合物可用于水合肺黏液分泌物和治疗肺疾病，如囊性纤维化，呼吸机相关性肺炎，慢性支气管炎，慢性阻塞性肺疾病和原发性纤毛运动障碍的方法。还描述了含有式I化合物的制药组合物和新的式I化合物。
• Uridine 5'-diphosphate and analogs useful for treating lung diseases
  申请人：The University of North Carolina at Chapel Hill

  公开号：US06143279A1

  公开（公告）日：2000-11-07

  Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ; X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H; R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

  公式I的化合物：##STR1## 其中：X.sub.1和X.sub.2各自独立地为O.sup.-或S.sup.-; X.sub.3和X.sub.4各自独立地为--H或--OH，但X.sub.3和X.sub.4不能同时为--H; R.sub.1从O，imido，methylene和dihalomethylene中选择; R.sub.2从H，halo，alkyl，substituted alkyl，alkoxyl，nitro和azido中选择; R.sub.3从H，alkyl，acyl，aryl和arylalkyl中选择; R.sub.4从--OR'，--SR'，--NR'和--NR'R"中选择，其中R'和R"各自独立地从H，alkyl，substituted alkyl，aryl，substituted aryl，arylalkyl，alkoxyl和aryloxyl中选择，但当R.sub.4从嘧啶环的4位碳原子上的氧或硫原子双键时，R'不存在。这些化合物可用于水合肺黏液分泌物和治疗肺部疾病，如囊性纤维化，呼吸机相关性肺炎，慢性支气管炎，慢性阻塞性肺疾病和原发性纤毛运动障碍等。还描述了含有公式I化合物的药物组合物和新的公式I化合物。
• 肺疾患を治療するためのウリジン５’−ジホスフェートとその類似体の使用
  申请人：ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル

  公开号：JP2001513568A

  公开（公告）日：2001-09-04

  \n (57)【要約】\n【課題】 肺疾患を治療する方法と、そのために有用な新規化合物と薬学的組成物を提供すること。\n【解決手段】 治療を必要とする被験者の肺の肺粘液分泌物を水和する方法であって、肺粘液の分泌物を水和するのに十分な量の下記の式Ｉの化合物またはその薬学的に許容可能な塩を被験者の肺に投与するステップを含んでなることを特徴とする。\n【化１】\n（式中、X1とX2は、各々独立にO-またはS-のどちらかであり、X3とX4は、各々独立に、−Hまたは−OHのどちらかであり、ただし、X3とX4は同時に−Hではなく、R1は、O、イミド、メチレンとジハロメチレンからなる群から選択され、R2は、H、ハロ、アルキル、置換アルキル、アルコキシ、ニトロとアジドからなる群から選択され、R3は、H、アルキル、アシル、アリールとアリールアルキルからなる群から選択され、R4は、−OR'、−SR'、−NR'と−NR'R''からなる群から選択され、ここのR'とR''は、独立に、H、アルキル、置換アルキル、アリール、置換アリール、アリールアルキル、アルコキシとアリールオキシからなる群から選択され、ただし、R4の酸素原子または硫黄原子とピリミジン環の4−位の炭素と結合が二重結合である場合は、R'は存在しない。）\n

  \(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)/(57)}Summary: To provide a method for treating lung diseases and a new compound and a pharmacological composition useful for such treatment.\Ўn[解]一种使需要治疗的受试者肺部的肺粘液分泌物水合化的方法，包括向受试者的肺部施用下式I的化合物或其药学上可接受的盐，施用量足以使肺粘液分泌物水合化。\Ϯn [Ϯ1] Ϯn (其中X1和X2各自独立地为O-或S-，X3和X4各自独立地为-H或-OH，条件是X3和X4不同时为-H，R1、选自由亚甲基和二卤代亚甲基组成的组，R2 选自由 H、卤代、烷基、取代烷基、烷氧基、硝基和叠氮化物组成的组，R3 选自由 H、烷基、酰基、芳基和芳烷基组成的组，R4 为选自由-OR'、-SR'、-NR'和-NR'R''组成的组，其中 R' 和 R'' 独立地为 H、烷基、取代的烷基、芳基、取代的芳基、选自芳基烷基、烷氧基和芳氧基组成的组，但如果 R4 的氧原子或硫原子与嘧啶环 4 位碳之间的键是双键，则不存在 R''）。\n