N-(trifluoroacetyl)-9,10-anhydrodaunorubicin | 68168-17-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: N-(trifluoroacetyl)-9,10-anhydrodaunorubicin
• 英文别名: 9,10-anhydro-N-(trifluoromethyl)daunorubicin；N-[(2S,3S,4S,6R)-6-[[(1S)-3-acetyl-5,12-dihydroxy-10-methoxy-6,11-dioxo-1,2-dihydrotetracen-1-yl]oxy]-3-hydroxy-2-methyloxan-4-yl]-2,2,2-trifluoroacetamide
• CAS: 68168-17-2
• 化学式: C₂₉H₂₆F₃NO₁₀
• 分子量: 605.521
• InChiKey: SPFMBHDFKNTCDY-LWSDYBGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  43
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  N-(trifluoroacetyl)-9,10-anhydrodaunorubicin 在 2,4,6-三甲基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 四氧化锇 、 偶氮二异丁腈 、 sodium hydrogensulfite 作用下， 以 吡啶 、 四氯化碳 为溶剂， 生成 N-[(2S,3S,4S,6S)-6-((1R,2S,3R,4S)-3-Acetyl-2-bromo-3,4,5,12-tetrahydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy)-3-hydroxy-2-methyl-tetrahydro-pyran-4-yl]-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  半合成高功能柔红霉素衍生物

  摘要：

  （4R ）从柔红霉素中获得了（8R，9S，10S）-9-脱氧-8，9-环氧-10-羟基柔红霉素（5）。关键反应是在9,10-脱水-N-三氟乙酰基柔红霉素的糖苷配基部分上的高度区域选择性和立体选择性的烯丙基溴化反应。

  DOI：

  10.1016/0040-4039(95)02321-6
• 作为产物：
  描述：

  三氟乙酰基柔红霉素 在 三氟乙酸酐 作用下， 以 吡啶 为溶剂， 以74%的产率得到N-(trifluoroacetyl)-9,10-anhydrodaunorubicin
  参考文献：
  名称：

  Adriamycin analogs. Preparation and biological evaluation of some N-perfluoroacyl analogs of daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate and their 9,10-anhydro derivatives

  摘要：

  The experimental and clinical antitumor activity, as well as the low toxicity, of N-(trifluoroacetyl)adriamycin 14-valerate (AD 32), a non-DNA binding anthracycline analogue, has led us to prepare and evaluate several N-perfluoroacyl analogues of daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate. Target compounds were prepared by reaction of the appropriate perfluoroacyl anhydride with daunorubicin in chloroform-ether, with adriamycin in cold pyridine, and with adriamycin 14-valerate in ethyl acetate. In connection with this work, it was found that reaction of perfluoroacyl anhydrides with N-acylated or N-unsubstituted anthracyclines in pyridine at room temperature afforded with ease and in good yield the corresponding 9,10-anhydro-N-acylated derivatives. A number of products showed good to highly significant antitumor activity in vivo against the murine P388 leukemia system. However, the lack of in vivo antitumor activity of the pentafluoropropionyl and heptafluorobutyryl analogues of N-(trifluoroacetyl)adriamycin 14-valerate is noteworthy. The results continue to show that non-DNA binding anthracycline analogues can exhibit in vivo antitumor activity. Loss of the anthracycline 9-carbinol function by dehydration leads to reduction of biological activity as compared to the parent compound.

  DOI：

  10.1021/jm00344a019

文献信息

• Adriamycin analogs. Preparation of 9,10-anhydrodaunorubicin, 9,10-anhydroadriamycin, and some related compounds
  作者：Gopalakrishnan Potti、Mervyn Israel

  DOI：10.1021/jm00346a027

  日期：1982.4

  The title compounds, as well as 9,10-anhydro-N-(trifluoroacetyl)adriamycin 14-valerate (9,10-anhydro-AD 32), were prepared starting from daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate (AD 32), respectively. In addition, 9-deoxydaunorubicin and 9-deoxy-AD 32 were obtained by catalytic hydrogenation of the appropriate olefin. All of the products were significantly less active

  从柔红霉素，阿霉素和N-（三氟乙酰基）阿霉素14-开始制备标题化合物以及9,10-脱水-N-（三氟乙酰基）阿霉素14-戊酸酯（9,10-脱水-AD 32）。戊酸（公元32年）。另外，通过适当的烯烃的催化氢化获得9-脱氧柔红霉素和9-脱氧-AD 32。所有产品在抑制培养物中CCRF-CEM（人类淋巴细胞白血病）细胞生长方面的活性均明显低于母体药物。结果表明，在蒽环霉素9位的母体化合物中发现，叔醇功能对于促进这些药物的生物活性表达非常重要。