5'-O-(tert-butoxycarbonyl)gemcitabine

• 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-(tert-butoxycarbonyl)gemcitabine
• 英文别名: [(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methyl tert-butyl carbonate
• 化学式: C₁₄H₁₉F₂N₃O₆
• 分子量: 363.318
• InChiKey: RGSPMZRUDOTVHG-SZEHBUNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 5'-O-(tert-butoxycarbonyl)gemcitabine 以 1,4-二氧六环 为溶剂， 反应 70.0h， 以65%的产率得到4-N-3'-O-bis(tert-butoxycarbonyl)gemcitabine
  参考文献：
  名称：

  吉西他滨-羧甲基多糖共轭物、制备方法及其用途

  摘要：

  本发明提出了一种吉西他滨‑羧甲基多糖共轭物、制备方法及制备抗肿瘤药物中的应用，本发明以羧甲基多糖作为药物载体，将不同的氨基酸连接体通过酯键或酰胺键连接至吉西他滨上，再将带有氨基酸连接体的吉西他滨偶联至羧甲基多糖的羧基上，得到吉西他滨‑羧甲基多糖共轭物，其可以显著增强吉西他滨的抗肿瘤活性，且在生理pH下稳定，在肿瘤部位的酸性微环境下水解缓慢释放吉西他滨，增强吉西他滨在肿瘤部位的富集，从而发挥被动靶向抗肿瘤作用，具有较高的安全性。本发明制备方法简单，产率高,因此在抗肿瘤方面具有广阔的开发前景。

  公开号：

  CN109481691A
• 作为产物：
  描述：

  盐酸吉西他滨 在 氢氧化钾 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 4.0h， 生成 5'-O-(tert-butoxycarbonyl)gemcitabine
  参考文献：
  名称：

  Selective Protection of 2‘,2‘-Difluorodeoxycytidine (Gemcitabine)

  摘要：

  Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH2, 5'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH2, 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PER ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.

  DOI：

  10.1021/jo9911140

文献信息

• Selective Protection of 2‘,2‘-Difluorodeoxycytidine (Gemcitabine)
  作者：Zhi-wei Guo、James M. Gallo

  DOI：10.1021/jo9911140

  日期：1999.10.1

  Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH2, 5'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH2, 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PER ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.
• 吉西他滨-羧甲基多糖共轭物、制备方法及其用途
  申请人：珠海天香苑生物科技发展股份有限公司

  公开号：CN109481691A

  公开（公告）日：2019-03-19

  本发明提出了一种吉西他滨‑羧甲基多糖共轭物、制备方法及制备抗肿瘤药物中的应用，本发明以羧甲基多糖作为药物载体，将不同的氨基酸连接体通过酯键或酰胺键连接至吉西他滨上，再将带有氨基酸连接体的吉西他滨偶联至羧甲基多糖的羧基上，得到吉西他滨‑羧甲基多糖共轭物，其可以显著增强吉西他滨的抗肿瘤活性，且在生理pH下稳定，在肿瘤部位的酸性微环境下水解缓慢释放吉西他滨，增强吉西他滨在肿瘤部位的富集，从而发挥被动靶向抗肿瘤作用，具有较高的安全性。本发明制备方法简单，产率高,因此在抗肿瘤方面具有广阔的开发前景。