formic acid 1,1-(ethylenedioxy)-5-oxo-7-propionyl-1,2,3,5-tetrahydroindolizin-6-ylmethyl ester | 863217-06-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: formic acid 1,1-(ethylenedioxy)-5-oxo-7-propionyl-1,2,3,5-tetrahydroindolizin-6-ylmethyl ester
• 英文别名: (5'-Oxo-7'-propanoylspiro[1,3-dioxolane-2,1'-2,3-dihydroindolizine]-6'-yl)methyl formate
• CAS: 863217-06-5
• 化学式: C₁₅H₁₇NO₆
• 分子量: 307.303
• InChiKey: WYQZBCBGPBNDLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  formic acid 1,1-(ethylenedioxy)-5-oxo-7-propionyl-1,2,3,5-tetrahydroindolizin-6-ylmethyl ester 在 水 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以93%的产率得到2',3'-dihydro-6'-(hydroxymethyl)-7'-(1-oxopropyl)spiro[1,3-dioxolane-2,1'(5'H)-indolizin]-5'-one
  参考文献：
  名称：

  喜树碱的合成研究。第三部分

  摘要：

  描述了一种简明有效的不对称过程，用于全合成（20 S）-7-乙基-10-羟基喜树碱（= SN-38; 1f），这是前药伊立替康的活性代谢形式。该方法的特点是在温和条件下由双官能硫脲基金鸡纳生物碱介导的吲哚嗪酮4的对映选择性氰基硅烷化反应，生成相应的氰醇5，以及I 2催化三环内酯6和2-氨基5-羟基苯丙酮的Friedländer缩合反应（ = 1-（2-氨基-5-羟基苯基）丙-1-酮）。

  DOI：

  10.1002/hlca.201000049
• 作为产物：
  描述：

  1,1-(ethylenedioxy)-8-ethyl-7,8-dihydroxy-1,2,3,5,7,8-hexahydro-6-oxa-3a-azacyclopenta[b]naphthalen-4-one 在 sodium periodate 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 0.5h， 以93.1%的产率得到formic acid 1,1-(ethylenedioxy)-5-oxo-7-propionyl-1,2,3,5-tetrahydroindolizin-6-ylmethyl ester
  参考文献：
  名称：

  New homocamptothecins: Synthesis, antitumor activity, and molecular modeling

  摘要：

  Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered beta-hydroxylactone in place of the conventional six-membered alpha-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 91, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.046

文献信息

• Phosphate ester derivatives of homocamptothecin: Synthesis, solution stabilities and antitumor activities
  作者：Zhenyuan Miao、Jing Zhang、Liang You、Juan Wang、Chunquan Sheng、Jiangzhong Yao、Wannian Zhang、Hao Feng、Wei Guo、Lei Zhou、Wenfeng Liu、Linjian Zhu、Pengfei Cheng、Xiaoying Che、Wenya Wang、Chuan Luo、Yulan Xu、Guoqiang Dong

  DOI：10.1016/j.bmc.2010.03.039

  日期：2010.5

  Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0. (c) 2010 Elsevier Ltd. All rights reserved.