5'-O-β-D-galactosyl-floxuridine | 163218-40-4

• 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: 5'-O-β-D-galactosyl-floxuridine
• 英文别名: 5-Gal-FUdR；5-fluoro-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]pyrimidine-2,4-dione
• CAS: 163218-40-4
• 化学式: C₁₅H₂₁FN₂O₁₀
• 分子量: 408.338
• InChiKey: ORDXFPJEBBQECJ-MHHJMVSLSA-N

物化性质

• 密度：
  1.73±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

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：
  0.73
• 拓扑面积：
  178
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-氟-2'-脱氧脲核苷 、 β-乳糖 在 β-galactosidase from Bacillus megaterium YZ08 作用下， 以 二甲基亚砜 为溶剂， 以18.8%的产率得到5'-O-β-D-galactosyl-floxuridine
  参考文献：
  名称：

  溶剂稳定的β-半乳糖苷酶催化在水性亲水性溶剂中核苷类似物的精确调节的半乳糖苷化†

  摘要：

  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。

  DOI：

  10.1039/c6ra12167e

文献信息

• 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.
• Biotransformation of 5´-O-β-d-galactosyl-floxuridine by immobilized β-galactosidase from Kocuria rhizophila
  作者：Andrea Sarquiz、Cintia W. Rivero、Claudia N. Britos、Jorge A. Trelles

  DOI：10.1016/j.jfluchem.2018.07.012

  日期：2018.10

  5-fluorouracil-2'-deoxyriboside (FUdR), an antimetabolite known as floxuridine, is a halogenated nucleoside extensively used in the clinical treatment of colon carcinoma and hepatic metastases. This drug presents low bioavailability, thus requiring large doses and frequent administration, which leads to long-lasting and severe side effects in clinical practice. In order to overcome this problem, galactosylated nucleoside analogues were obtained using immobilized beta-galactosidase in Ca-alginate with yields of 80% at only 7 h. Additionally, the obtained biocatalyst was stable for 6 months in storage conditions (4 degrees C) and could be reused at least 16 times without loss of its activity at 30 degrees C.This work describes for the first time an efficient, eco-compatible and simple bioprocess for obtaining 5'-O-beta-D-galactosyl-floxuridine using an immobilized biocatalyst.
• 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。