[(2R,3R,4R,5R)-4-acetyloxy-5-[5-fluoro-2-oxo-4-[(3,4,5-trimethoxybenzoyl)amino]pyrimidin-1-yl]-2-methyloxolan-3-yl] acetate | 161599-31-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: [(2R,3R,4R,5R)-4-acetyloxy-5-[5-fluoro-2-oxo-4-[(3,4,5-trimethoxybenzoyl)amino]pyrimidin-1-yl]-2-methyloxolan-3-yl] acetate
• CAS: 161599-31-1
• 化学式: C₂₃H₂₆FN₃O₁₀
• 分子量: 523.472
• InChiKey: HGIRBCFJVPRNSE-YJABCAQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  151
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-4-acetyloxy-5-[5-fluoro-2-oxo-4-[(3,4,5-trimethoxybenzoyl)amino]pyrimidin-1-yl]-2-methyloxolan-3-yl] acetate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.03h， 以78.2 mg的产率得到加洛他滨
  参考文献：
  名称：

  布朗斯台德酸催化糖基化快速连续合成流动中的5'-脱氧核糖核苷

  摘要：

  在几种重要的5'-脱氧核糖核苷药物的单流，多步合成中，一般的，绿色的，有效的布朗斯台德酸催化的糖基化是关键一步。

  DOI：

  10.1021/ol301324g
• 作为产物：
  描述：

  1,2,3-三乙酰氧基-5-脱氧-D-核糖 在 吡啶 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.0h， 生成 [(2R,3R,4R,5R)-4-acetyloxy-5-[5-fluoro-2-oxo-4-[(3,4,5-trimethoxybenzoyl)amino]pyrimidin-1-yl]-2-methyloxolan-3-yl] acetate
  参考文献：
  名称：

  The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine

  摘要：

  To identify an orally available fluoropyrimidine having efficacy and safety profiles greatly improved over those of parenteral 5-fluorouracil (5-FU: 1), we designed a 5-FU prodrug that would pass intact through the intestinal mucisa and be sequentially converted to 5-FU by enzymes that are highly expressed in the human liver and then in tumors. Among various N-4-substituted 5'-deoxy-5-fluorocytidine derivatives, a series of N-4-alkoxycarbonyl derivatives were hydrolyzed to 5'-deoxy-5-fluoro-cytidine (5'-DFCR: 8) specifically by carboxylesterase, which exists preferentially in the liver in humans and monkeys. Particularly, derivatives having an N-4-alkoxylcarbonyl moiety with a C4-C6 alkyl chain were the most susceptible to the human carboxylesterase. Those were then converted to 5'-deoxy-5-fluorouridine (5'-DFUR: 4) by cytidine deaminase highly expressed in the liver and solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in turners. When administered orally to monkeys, a derivative having the N-4-alkoxylcarbonyl moiety with a C5 alkyl chain (capecitabine: 6) The highest AUC and Cmax for plasma 5'-DFUR. In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00087-0

文献信息

• Synthesis of Nucleosides and Deoxynucleosides via Gold(I)-Catalyzed <i>N</i>-Glycosylation of Glycosyl (<i>Z</i>)-Ynenoates
  作者：Rongkun Liu、Yan Chen、Jibin Zheng、Lvfeng Zhang、Tong Xu、Peng Xu、You Yang

  DOI：10.1021/acs.orglett.2c03964

  日期：2022.12.30

  with purines was found to be very effective for regioselective synthesis of pyranosyl N9 purine nucleosides. Based on the catalytic N-glycosylation approach, convenient synthesis of two 5′-deoxynucleosides drugs (capecitabine and galocitabine), four 2′-deoxynucleoside drugs (floxuridine, trifluridine, decitabine and cladribine), four 3′,5′-dideoxynucleoside analogues, and four 2′,5′-dideoxynucleoside

  核苷类似物广泛用作抗癌和抗病毒药物。在这里，我们开发了一种高效的金（I）催化的N-糖基化方法，用于以糖基（Z）-炔酸作为供体合成各种类型的核苷和脱氧核苷。31 个嘧啶核苷和 8 个嘌呤核苷的合成证明了N-糖基化方法的广泛范围。值得注意的是，金（I）催化的吡喃糖基（Z ）-炔酸酯与嘌呤的N-糖基化被发现对于吡喃糖基N9嘌呤核苷的区域选择性合成非常有效。基于催化N-糖基化方法，方便合成两种5'-脱氧核苷药物（卡培他滨和加西他滨）、四种2'-脱氧核苷药物（氟尿苷、三氟尿苷、地西他滨和克拉屈滨）、四种3',5'-双脱氧核苷类似物，并集体获得了4个2',5'-双脱氧核苷类似物。
• Novel process for producing N4-acyl-5'-deoxy-5-fluorocytidine derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0602478B1

  公开（公告）日：1996-07-31
• Rapid Continuous Synthesis of 5′-Deoxyribonucleosides in Flow via Brønsted Acid Catalyzed Glycosylation
  作者：Bo Shen、Timothy F. Jamison

  DOI：10.1021/ol301324g

  日期：2012.7.6

  A general, green, and efficient Brønsted acid-catalyzed glycosylation serves as a key step in the one-flow, multistep syntheses of several important 5′-deoxyribonucleoside pharmaceuticals.

  在几种重要的5'-脱氧核糖核苷药物的单流，多步合成中，一般的，绿色的，有效的布朗斯台德酸催化的糖基化是关键一步。
• The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine
  作者：Nobuo Shimma、Isao Umeda、Motohiro Arasaki、Chikako Murasaki、Kazunao Masubuchi、Yasunori Kohchi、Masanori Miwa、Masako Ura、Noriaki Sawada、Hitoshi Tahara、Isamu Kuruma、Ikuo Horii、Hideo Ishitsuka

  DOI：10.1016/s0968-0896(00)00087-0

  日期：2000.7

  To identify an orally available fluoropyrimidine having efficacy and safety profiles greatly improved over those of parenteral 5-fluorouracil (5-FU: 1), we designed a 5-FU prodrug that would pass intact through the intestinal mucisa and be sequentially converted to 5-FU by enzymes that are highly expressed in the human liver and then in tumors. Among various N-4-substituted 5'-deoxy-5-fluorocytidine derivatives, a series of N-4-alkoxycarbonyl derivatives were hydrolyzed to 5'-deoxy-5-fluoro-cytidine (5'-DFCR: 8) specifically by carboxylesterase, which exists preferentially in the liver in humans and monkeys. Particularly, derivatives having an N-4-alkoxylcarbonyl moiety with a C4-C6 alkyl chain were the most susceptible to the human carboxylesterase. Those were then converted to 5'-deoxy-5-fluorouridine (5'-DFUR: 4) by cytidine deaminase highly expressed in the liver and solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in turners. When administered orally to monkeys, a derivative having the N-4-alkoxylcarbonyl moiety with a C5 alkyl chain (capecitabine: 6) The highest AUC and Cmax for plasma 5'-DFUR. In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. (C) 2000 Elsevier Science Ltd. All rights reserved.