5'-O-decanoyl-floxuridine | 118694-12-5

• 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-decanoyl-floxuridine
• 英文别名: 5'-O-decanoyl-FUdR；[(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl decanoate
• CAS: 118694-12-5
• 化学式: C₁₉H₂₉FN₂O₆
• 分子量: 400.447
• InChiKey: KACBFRVLAZGKBW-ARFHVFGLSA-N

物化性质

• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3',5'-O-didecanoyl-floxuridine 在 porcine liver esterase 作用下， 以 水 为溶剂， 生成 3'-O-decanoyl-floxuridine 、 5'-O-decanoyl-floxuridine 、 5-氟-2'-脱氧脲核苷
  参考文献：
  名称：

  Activity of esterase in the hydrolysis of 3',5'-diesters of 5-fluoro-2'-deoxyuridine in relation to the structure of the diester prodrugs.

  摘要：

  研究了猪肝脏酯酶对 5-氟-2'-脱氧尿苷与饱和脂肪族酸（包括乙酸、丙酸、丁酸、己酸、辛酸、癸酸和十二酸）的二酯的活性。随着酰基链延长至辛酰，3', 5'-二酯的易感性增加，但酰基链长度的进一步增加导致易感性急剧下降。3'-和 5'-单酯的敏感性随着酰基链延长到癸酰基而增加，当延长到十二酰基时则略有下降。这些结果表明，5-氟-2'-脱氧尿苷的长烷基链二酯具有较高的抗肿瘤活性，部分原因是它们被非特异性酯酶水解的速度较慢。

  DOI：

  10.1248/cpb.33.301

文献信息

• Influence of substituent groups in regioselective acylation of nucleosides by Novozym 435 lipase
  作者：Zhao-Yu Wang、Yan-Hong Bi、Xiang-Qian Li、Min-Hua Zong

  DOI：10.1016/j.procbio.2013.06.022

  日期：2013.8

  comparative study on the substrate recognition was conducted successfully in Novozym 435-mediated acylation of various 2′- or 5-substituted nucleosides with acyl donors carrying different aliphatic chain lengths (C6, C10, and C14). The unexpected results revealed that the physicochemical property of the substituents (such as the size, hydrophobicity, and substitutional position) in nucleosides profoundly influenced

  在 Novozym 435 介导的各种 2' 或 5 取代核苷与携带不同脂肪链长度（C6、C10 和 C14）的酰基供体的酰化中，成功地进行了底物识别的比较研究。出乎意料的结果表明，核苷中取代基的物理化学性质（如大小、疏水性和取代位置）对酶的行为产生了深远的影响。源自核苷 2'-或 5-位取代基的不同底物结合模式可以解释这一点。此外，除了脂肪酶活性位点的几何构型之外，控制区域选择性的另一个可能因素可能归因于取代基和酰基供体之间的相互作用。
• Regioselective Acylation of Nucleosides Catalyzed by<i>Candida Antarctica</i>Lipase B: Enzyme Substrate Recognition
  作者：Ning Li、Min-Hua Zong、Ding Ma

  DOI：10.1002/ejoc.200800780

  日期：2008.11

  The substrate recognition of Candida antarctica lipase B (CAL-B) in the acylation of nucleosides was revealed through rational substrate engineering for the first time. CAL-B displayed lower activities and excellent 5-regioselectivities (94 to 99 %) in the acylation of ribonucleosides 1f–1j as compared to those in the acylation of 2-deoxynucleosides 1a– 1e. The excellent regioselectivities might be

  首次通过合理的底物工程揭示了南极念珠菌脂肪酶B（CAL-B）在核苷酰化中的底物识别。与 2-脱氧核苷 1a-1e 的酰化相比，CAL-B 在核糖核苷 1f-1j 的酰化中表现出较低的活性和优异的 5-区域选择性（94% 至 99%）。优异的区域选择性可能归因于存在于 2-羟基中的有利的空间位阻
• Activity of esterase in the hydrolysis of 3',5'-diesters of 5-fluoro-2'-deoxyuridine in relation to the structure of the diester prodrugs.
  作者：TAKEO KAWAGUCHI、YOSHIKI SUZUKI、YOKO NAKAHARA、NAOKI NAMBU、TSUNEJI NAGAI

  DOI：10.1248/cpb.33.301

  日期：——

  The activity of porcine liver esterase towards diesters of 5-fluoro-2'-deoxyuridine with saturated aliphatic acids including acetic, propionic, butyric, hexanoic, octanoic, decanoic and dodecanoic acids was investigated. The susceptibility of the 3', 5'-diesters increased as the acyl chain was lengthened up to octanoyl, but further increase in the acyl chain length resulted in a sharp decrease in the susceptibility. The susceptibility of 3'-and 5'-monoesters increased as the chain was lengthened to decanoyl and slightly decreased on going to dodecanoyl. These results suggest that the higher antitumor activity of longer alkyl chain diesters of 5-fluoro-2'-deoxyuridine is partly due to their slow rates of hydrolysis by non-specific esterase.

  研究了猪肝脏酯酶对 5-氟-2'-脱氧尿苷与饱和脂肪族酸（包括乙酸、丙酸、丁酸、己酸、辛酸、癸酸和十二酸）的二酯的活性。随着酰基链延长至辛酰，3', 5'-二酯的易感性增加，但酰基链长度的进一步增加导致易感性急剧下降。3'-和 5'-单酯的敏感性随着酰基链延长到癸酰基而增加，当延长到十二酰基时则略有下降。这些结果表明，5-氟-2'-脱氧尿苷的长烷基链二酯具有较高的抗肿瘤活性，部分原因是它们被非特异性酯酶水解的速度较慢。