1-<2'-deoxy-5'-β-D-galactopyranosyl-β-D-ribofuranosyl>thymine

• 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: 1-<2'-deoxy-5'-β-D-galactopyranosyl-β-D-ribofuranosyl>thymine
• 英文别名: (β-D-galactopyranosyl)-(1-5')-O-2'-deoxy-β-D-ribofuranosylthymine；5'-O-β-D-galactopyranosyl-2'-thymidine；thymidine 5-O-β-D-galactoside；Gal(b1-5)2-deoxy-D-eryPenf(b)-thymin-1-yl；1-[(2R,4S,5R)-4-hydroxy-5-[[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₆H₂₄N₂O₁₀
• 分子量: 404.374
• InChiKey: ZJUSUKBJYFWBSN-OAOVJFGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  178
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3'-O-acetylthymidine 在 4 A molecular sieve 、 三氟化硼乙醚 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.67h， 生成 1-<2'-deoxy-5'-β-D-galactopyranosyl-β-D-ribofuranosyl>thymine
  参考文献：
  名称：

  Differential reactivity of carbohydrate hydroxyls in glycosylations. II. The likely role of intramolecular hydrogen bonding on glycosylation reactions. Galactosylation of nucleoside 5′-hydroxyls for the syntheses of novel potential anticancer agents

  摘要：

  与预期相反，许多主要的羟基在糖基化反应中完全不活跃，或者以非常低的产率给出所需的糖苷，伴随着许多副反应产物。这些主要羟基的氢被显示为分子内氢键结合。由这些羟基对活化的糖基化试剂的亲核攻击形成的中间体可能会抵抗氢的提取。据推测，这种抵抗质子损失的现象是观察到的不活性的起源。研究表明，成功的糖基化反应发生在酸性条件下，这种条件下这种氢键不再存在。因此，首次利用三氯乙酰亚胺盐酸镓在氯仿中在三氟乙酸银的促进下，成功地对核苷的通常不活跃的5'-羟基进行了直接的半乳糖化。据指出，这种半乳糖化的抗癌核苷可能具有改善的生物特异性。

  DOI：

  10.1139/v94-284

文献信息

• Synthesis of Disaccharide Nucleosides by the<i>O</i>-Glycosylation of Natural Nucleosides with Thioglycoside Donors
  作者：Shin Aoki、Taketo Fukumoto、Taiki Itoh、Masayuki Kurihara、Shigeto Saito、Shin-ya Komabiki

  DOI：10.1002/asia.201403319

  日期：2015.3

  Disaccharide nucleosides constitute an important group of naturally‐occurring sugar derivatives. In this study, we report on the synthesis of disaccharide nucleosides by the direct O‐glycosylation of nucleoside acceptors, such as adenosine, guanosine, thymidine, and cytidine, with glycosyl donors. Among the glycosyl donors tested, thioglycosides were found to give the corresponding disaccharide nucleosides

  二糖核苷是天然存在的糖衍生物的重要组成部分。在这项研究中，我们报道了通过核苷受体（如腺苷，鸟苷，胸苷和胞苷）与糖基供体的直接O-糖基化来合成二糖核苷。在测试的糖基供体中，发现硫代糖苷可以使用对甲苯磺酰氯（TolSCl）和三氟甲磺酸银（AgOTf）作为促进剂，以上述核苷受体以中等至高化学产率提供相应的二糖核苷。通过1 H NMR光谱实验检查了这些启动子与核苷受体的相互作用。
• Precisely regulated galactosylation of nucleoside analogues in aqueous hydrophilic solvents catalyzed by solvent-stable β-galactosidase
  作者：Youzhi Zhou、Jianlin Chu、Jinsong Zhang、Ke Liu、Bingfang He

  DOI：10.1039/c6ra12167e

  日期：——

  digalactosyl nucleoside analogues in the buffer system. The addition of DMSO not only prominently increased the stabilization of β-galactosidase but also regulated the products from complicated products to unitary monogalactosyl nucleoside analogues, which could significantly simplify the process of subsequent separation. Strikingly, the affinity of β-galactosidase to 3′-azido-3′-deoxythymidine in 10% DMSO was

  在10％DMSO溶剂系统中成功地合成了有效的合成β-半乳糖基核苷类似物，该方法由耐溶剂的巨大芽孢杆菌中新分离的溶剂稳定的β-半乳糖苷酶催化YZ08。用于核苷类似物的半乳糖基化的最有效的糖供体是乳糖而不是硝基苯基糖苷。然而，它伴随着在缓冲系统中形成复杂的二半乳糖基核苷类似物。DMSO的加入不仅显着提高了β-半乳糖苷酶的稳定性，而且还调节了从复杂产物到单一单半乳糖基核苷类似物的产物，这可以显着简化后续分离的过程。令人惊讶的是，在10％DMSO中，β-半乳糖苷酶对3'-叠氮基3'-脱氧胸苷的亲和力显着增强，催化效率（k cat / K m与缓冲溶液相比）增加了一倍。这些结果表明，通过调节反应溶剂系统，溶剂稳定的糖苷酶在生物合成以及糖苷前药的调节中具有诱人的效力。
• Galactosylation by use of β-galactosidase: Enzymatic syntheses of disaccharide nucleosides
  作者：Wolfgang H. Binder、Hanspeter Kählig、Walther Schmid

  DOI：10.1016/0957-4166(95)00216-c

  日期：1995.7

  synthesis of various galactose containing disaccharide nucleosides has been achieved by utilizing the transgalactosylation potential of ß-galactosidase from Aspergillus oryzae. Thus, using p-nitrophenyl-ß-D-galactoside 1 as galactosyl donor, 2-deoxyuridine 2a, uridine 2b, thymidine 2c and adenosine 2d have proven to be useful acceptors for the enzyme catalyzed disaccharide nucleoside formation. The regiochemistry

  通过利用米曲霉中β-半乳糖苷酶的反式半乳糖基化潜力，已经实现了各种含半乳糖的二糖核苷的合成。因此，使用对硝基苯基-β-D-半乳糖苷1作为半乳糖基供体，已证明2-脱氧尿苷2a，尿苷2b，胸苷2c和腺苷2d对于酶催化的二糖核苷形成是有用的受体。乙酰化后形成的产物4a-4d的区域化学已经使用现代NMR技术明确分配。
• Compositions and methods for targeted enzymatic release of cell regulatory compounds
  申请人：Marker Gene Technologies, Inc.

  公开号：US20040101932A1

  公开（公告）日：2004-05-27

  Novel pro-drugs and methods for their use to alter the growth and biological characteristics of living cells, tissues, or whole organisms are described. The methods allow for selective activation of the pro-drugs at or near transformant host cells expressing a gene for an enzyme that activates the pro-drugs. Pro-drugs according to a preferred embodiment of the invention are conjugates of a bioactive compound and a chemical group that is capable of being cleaved from the bioactive compound by action of an enzyme. Methods according to this invention include, (a) introducing into targeted cells a gene encoding an enzyme and (b) administering a pro-drug, wherein the enzyme releases the pro-drug from conjugation. In a preferred embodiment of the invention, the gene encoding the enzyme is a marker gene.

  本发明描述了一种新型的前药及其使用方法，用于改变生物细胞、组织或整个生物的生长和生物学特征。该方法允许在表达激活前药酶基因的转化宿主细胞附近或接近处选择性地激活前药。根据本发明的一种优选实施方式，前药是生物活性化合物和化学基团的结合物，该化学基团能够通过酶的作用从生物活性化合物中被裂解。本发明的方法包括：(a)将编码酶的基因引入靶向细胞中；(b)给予前药，其中酶释放结合的前药。在本发明的一种优选实施方式中，编码酶的基因是标记基因。
• Facile and regioselective enzymatic 5′-galactosylation of pyrimidine 2′-deoxynucleosides catalyzed by β-glycosidase from bovine liver
  作者：Min Ye、Li-Qiang Yan、Ning Li、Min-Hua Zong

  DOI：10.1016/j.molcatb.2012.03.018

  日期：2012.7

  A regioselective enzymatic approach to 5'-O-galactosylated derivatives of pyrimidine 2'-deoxynucleosides was described. With o-nitrophenyl beta-D-galactoside as glycosyl donor, galactosylation reactions of 2'-deoxynucleosides were mediated by a commercial beta-galactosidase from bovine liver, affording 5'-O-galactosylated derivatives with the yields of 45-85% and 5'-regioselectivities of 92-100%. The study of enzyme substrate recognition revealed that the beta-galactosidase performance showed a clear dependence on R-group present in the base moiety of 2'-deoxynucleoside. Besides, such desirable products were synthesized with satisfactory yields (41-68%) and moderate to high 5'-regioselectivities (87-100%) by using the crude enzyme extract. (C) 2012 Elsevier B.V. All rights reserved.