2',3',5'-tri-O-benzoyl-L-uridine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2',3',5'-tri-O-benzoyl-L-uridine
• 英文别名: 1-(2,3,5-Tri-O-benzoyl-beta-L-ribofuranosyl)uracil；[(2S,3S,4S,5S)-3,4-dibenzoyloxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate
• 化学式: C₃₀H₂₄N₂O₉
• 分子量: 556.529
• InChiKey: MPYUTOYNCCRZAC-GKXKVECMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2',3',5'-tri-O-benzoyl-L-uridine 在 磷酸三乙酯 、 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 23.0h， 生成 UMP
  参考文献：
  名称：

  First synthesis of enantio-uracil dinucleotide, comparison of physicochemical properties of their enantiomers, and separation by chiral column chromatography

  摘要：

  Enantio-uracil dinucleotide 5, which consists Of two L-uridylic acids and one pyrophosphate, was synthesized for the first time in our laboratory. Benzolyated L-uridine was prepared by a stereoselective glycosylation of silylated uracil with L-1-O-acetyl-2,3,5-tri-O-benzoylribose (L-ABR 7). After deprotection, L-uridine 9 was converted to P-1,P-4-di(L-uridine 5'-) tetraphosphate tetrasodium salt (L-UP4U 5) by treatment of L-UMP morpholidate 10c with triethylammonium pyrophosphate (TEA-PPi 11b). Spectral data of synthesized L-Up(4)U 5 are given in the references. All spectral data were identical with those of UP4U 3 except the specific rotation, which showed a positive value compared to UP,U 3 having a negative value. Furthermore, the separation by chiral column chromatography was investigated. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.09.142
• 作为产物：
  描述：

  1-O-methyl-2,3,5-tri-O-benzoyl-L-ribofuranose 在 苯磺酰胺 、 三氟甲磺酸三甲基硅酯 、 硫酸 作用下， 以 溶剂黄146 、 乙腈 为溶剂， 生成 2',3',5'-tri-O-benzoyl-L-uridine
  参考文献：
  名称：

  L-木糖中的L-核糖核苷

  摘要：

  通过氧化/还原程序将L-木糖转化为L-核糖衍生物。根据Vorbrüggen的条件，使L-核糖基供体进行糖苷化反应，以高产率得到L-核糖核苷（L-尿苷，L-胞苷，L-腺苷和L-鸟苷）。

  DOI：

  10.1016/s0040-4020(98)01119-3

文献信息

• [EN] MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS OLIGOMÈRES MODIFIÉS ET LEURS UTILISATIONS
  申请人：IONIS PHARMACEUTICALS INC

  公开号：WO2021030763A1

  公开（公告）日：2021-02-18

  The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.

  本公开提供了包含至少一种立体非标准核苷酸的修饰寡核苷酸的寡聚化合物。包括由12-30个连接的核苷酸组成的修饰寡核苷酸的寡聚化合物，其中修饰寡核苷酸的至少一个核苷酸是立体非标准核苷酸；且所述寡聚化合物选自RNAi化合物、修饰CRISPR化合物和人工mRNA化合物。
• Preparation, antibacterial effects and enzymatic degradation of 5-fluorouracil nucleosides
  作者：Beatrice Schwarz、Dieter Cech、Antonín Holý、Jan Škoda

  DOI：10.1135/cccc19803217

  日期：——

  Reaction of perbenzoylated aldopentafuranosyl derivatives of uracil with fluorine in acetic acid afforded perbenzoylated 5-fluorouracil nucleosides. Their methanolysis gave the following free nucleosides of 5-fluorouracil: β-D-ribofuranoside (Id), 2-deoxy-β-D-ribofuranoside (IId), their enantiomers VIII and IX, α-D-ribofuranoside (XIII), 2-deoxy-α-D-ribofuranoside (XV), β-D-arabinofuranoside (IV) and its L-enantiomer X, β-D-xylofuranoside (V) and its α-D-anomer XI, α-L-lyxofuranoside (VI) and 2-deoxy-α-L-lyxofuranoside (VII) and the enantiomers of the latter two compounds, XII and XIV, respectively. Analogously were obtained 5-deoxy-β-D-ribofuranoside (III), β-D-ribopyranoside (XVI) and 1-(S)-(2,3-dihydroxypropyl)-5-fluorouracil (XVIIc). 1-Allyl-5-fluorouracil (XVIII) was prepared by reaction of allyl bromide with 2,4-bis(trimethylsilyloxy)-5-fluoropyrimidine. The cell-free extract from Escherichia coli cleaves all the 5-fluorouracil nucleosides in which the nucleoside carbon atom has the R-configuration and the 3'-hydroxyl of the sugar moiety is in trans-relation to the base. Compounds which have not these structural features are resistant. Besides nucleosides which on enzymatic cleavage afford 5-fluorouracil, also the non-cleavable 1-(2-deoxy-β-L-ribofuranosyl)-5-fluorouracil (IX), 1-(2-deoxy-α-D-ribofuranosyl)-5-fluorouracil (XV) and 1-(2-deoxy-α-D-lyxofuranosyl)-5-fluorouracil (XIV) exhibit an antibacterial effect towards E. coli (ID₅₀ 1.0-2.5 . 10^-5 M). This effect can be reversed by 2'-deoxyuridine but not by thymidine.

  在冰乙酸中，尿嘧啶的苄酰化醛基五糖衍生物与氟反应生成了苄酰化的5-氟尿嘧啶核苷。它们的甲醇解产生了以下的游离5-氟尿嘧啶核苷：β-D-核糖呋喃苷（Id）、2-脱氧-β-D-核糖呋喃苷（IId）、它们的对映异构体VIII和IX、α-D-核糖呋喃苷（XIII）、2-脱氧-α-D-核糖呋喃苷（XV）、β-D-阿拉伯呋喃苷（IV）及其L-对映体X、β-D-木糖呋喃苷（V）及其α-D-异构体XI、α-L-吕糖呋喃苷（VI）和2-脱氧-α-L-吕糖呋喃苷（VII）以及后两种化合物的对映体XII和XIV。类似地获得了5-脱氧-β-D-核糖呋喃苷（III）、β-D-核糖吡喃苷（XVI）和1-(S)-(2,3-二羟基丙基)-5-氟尿嘧啶（XVIIc）。1-丙烯基-5-氟尿嘧啶（XVIII）是通过丙烯基溴和2,4-双(三甲基硅氧基)-5-氟嘧啶反应制备的。大肠杆菌的细胞提取物可裂解所有5-氟尿嘧啶核苷，其中核苷碳原子具有R-构型，糖基的3'-羟基与碱基呈反式关系。不具备这些结构特征的化合物是抗性的。除了在酶解时产生5-氟尿嘧啶的核苷外，还有不可裂解的1-(2-脱氧-β-L-核糖呋喃基)-5-氟尿嘧啶（IX）、1-(2-脱氧-α-D-核糖呋喃苷)-5-氟尿嘧啶（XV）和1-(2-脱氧-α-D-吕糖呋喃苷)-5-氟尿嘧啶（XIV）对大肠杆菌表现出抗菌作用（ID50为1.0-2.5 x 10^-5 M）。这种效应可以被2'-脱氧尿苷而不是胸苷逆转。
• Enantioselective synthesis and biological evaluation of 5-o-carboranyl pyrimidine nucleosides
  作者：Nicolas S. Mourier、Alessandra Eleuteri、Selwyn J. Hurwitz、Phillip M. Tharnish、Raymond F. Schinazi

  DOI：10.1016/s0968-0896(99)00222-9

  日期：1999.12

  several 5-o-carboranyl-containing nucleosides. These derivatives may possess favorable properties such as high lipophilicity, high transportability, the ability to be phosphorylated, and resistance to catabolism. Beta-isomers of 2',3'-dihydroxynucleosides and analogues containing a heteroatom in the sugar moiety were also synthesized. Carboranyl pyrimidine nucleosides were prepared either from the parent

  当与中子结合时，碱修饰的含碳硼烷的核苷，例如5-o-碳硼烷基-2'-脱氧尿苷（CDU），具有治疗某些恶性肿瘤的潜力。对于用于脑肿瘤和其他恶性肿瘤的硼中子捕获疗法（BNCT）中使用的修饰核苷，各种细胞中缺乏毒性，癌细胞中的高积累和细胞内磷酸化是理想的特性。这项工作的目的是合成几种含5-o-碳烷基的核苷的两个β-对映体。这些衍生物可具有有利的性质，例如高亲脂性，高运输性，被磷酸化的能力以及对分解代谢的抵抗力。还合成了2'，3'-二羟基核苷的β-异构体和糖部分含杂原子的类似物。碳硼烷基嘧啶核苷可以由母体β-D-核苷，β-L-核苷或通过偶联反应制备。二氧戊环衍生物7是通过受保护的5-o-碳氧烷基尿嘧啶（8，CU）与相应的受保护的杂环之间的偶联反应制备的。在N-糖基化过程中使用了特定的催化剂以促进β-异构体的形成。这些新的手性5-o-碳硼烷基嘧啶衍生物的生物学评估表明，这些化合物中的大多数在多种正常
• L-ribofuranosyl nucleosides
  申请人：Genencor International, Inc.

  公开号：US05559101A1

  公开（公告）日：1996-09-24

  This invention relates to .alpha. and .beta. L-ribofuranosyl nucleosides, processes for their preparation, pharmaceutical compositions containing them, and methods of using them to treat various diseases in mammals.

  本发明涉及α和β L-核糖呋喃核苷，其制备过程，包含它们的制药组合物以及使用它们治疗哺乳动物的各种疾病的方法。
• In Vitro and In Silico Studies of Human Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibition by Stereoisomeric Forms of Lipophilic Nucleosides: The Role of Carbohydrate Stereochemistry in Ligand-Enzyme Interactions
  作者：Nadezhda S. Dyrkheeva、Irina A. Chernyshova、Georgy A. Ivanov、Yuri B. Porozov、Anastasia A. Zenchenko、Vladimir E. Oslovsky、Alexandra L. Zakharenko、Darina I. Nasyrova、Galina N. Likhatskaya、Sergey N. Mikhailov、Olga I. Lavrik、Mikhail S. Drenichev

  DOI：10.3390/molecules27082433

  日期：——

  phosphodiesterase 1 (Tdp1) by different chiral lipophilic nucleoside derivatives was studied. New Tdp1 inhibitors were found in the series of the studied compounds with IC50 = 2.7–6.7 μM. It was shown that D-lipophilic nucleoside derivatives manifested higher inhibition activity than their L-analogs, and configuration of the carbohydrate moiety can influence the mechanism of Tdp1 inhibition.

  研究了不同手性亲脂性核苷衍生物对人 DNA 修复酶酪氨酰-DNA 磷酸二酯酶 1 (Tdp1) 的抑制作用。在一系列研究化合物中发现了新的 Tdp1 抑制剂，IC 50 = 2.7–6.7 μM。结果表明，D-亲脂性核苷衍生物比它们的 L-类似物表现出更高的抑制活性，并且碳水化合物部分的构型可以影响 Tdp1 抑制的机制。