2E-3-((3S,4S,4aS,5S,6S,7R,8aR)-3,4,4a,5,6,7,8,8a-octahydro-6-(tertbutyldimethylsiloxy)-3,5,7-trimethylnaphthalen-4-yl)acrylic acid | 1417091-40-7

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 2E-3-((3S,4S,4aS,5S,6S,7R,8aR)-3,4,4a,5,6,7,8,8a-octahydro-6-(tertbutyldimethylsiloxy)-3,5,7-trimethylnaphthalen-4-yl)acrylic acid
• 英文别名: (E)-3-[(1S,2S,4aR,6R,7S,8S,8aS)-7-[tert-butyl(dimethyl)silyl]oxy-2,6,8-trimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]prop-2-enoic acid
• CAS: 1417091-40-7
• 化学式: C₂₂H₃₈O₃Si
• 分子量: 378.627
• InChiKey: QQAWUBZYSXTZRR-ZTDJZQFZSA-N

物化性质

• 沸点：
  445.8±45.0 °C(predicted)
• 密度：
  0.99±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.75
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2E-3-((3S,4S,4aS,5S,6S,7R,8aR)-3,4,4a,5,6,7,8,8a-octahydro-6-(tertbutyldimethylsiloxy)-3,5,7-trimethylnaphthalen-4-yl)acrylic acid 在 盐酸 、 4-二甲氨基吡啶 、 2-甲基-6-硝基苯甲酸酐 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 26.17h， 生成 2E-3-((3S,4S,4aS,5S,6S,7R,8aR)-3,4,4a,5,6,7,8,8a-octahydro-6-hydroxy-3,5,7-trimethylnaphthalen-4-yl)-N-((pyridin-3-yl)methyl)acrylamide
  参考文献：
  名称：

  Total Synthesis of AMF-26, an Antitumor Agent for Inhibition of the Golgi System, Targeting ADP-Ribosylation Factor 1

  摘要：

  An effective method for the total synthesis of 1 (AMF-26), a potentially promising new anticancer drug that disrupts the Golgi system by inhibiting the ADP-ribosylation factor 1 (Arf1) activation, has been developed for the first time. The construction of the chiral linear precursor (a key to the synthesis) was achieved by the asymmetric aldol reaction followed by the computer-assisted predictive stereoselective intramolecular Diels-Alder reaction. The global antitumor activity of the totally synthetic 1 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR39), and it was shown that the synthetic 1 strongly inhibited the growth of several cancer cell lines at concentrations of less than 0.04 mu M. Biological assays of novel derivatives, 26 and 31, which have different side-chains at the C-4 positions in the Delta(1,2)-octalin backbone, disclosed the importance of the suitable structure of the side-chain containing conjugated multidouble bonds.

  DOI：

  10.1021/jm301695c
• 作为产物：
  描述：

  sorbyl bromide 在 2,6-二甲基吡啶 、 lithium aluminium tetrahydride 、 tin(II) trifluoromethanesulfonate 、 四丙基高钌酸铵 、 (R)-1-methyl-2-(1-naphthylaminomethyl)pyrrolidine 、 sodium hexamethyldisilazane 、 氯化二乙基铝 、 二异丁基氢化铝 、 二乙酸二丁基锡 、 N-甲基吗啉氧化物 、 lithium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 65.91h， 生成 2E-3-((3S,4S,4aS,5S,6S,7R,8aR)-3,4,4a,5,6,7,8,8a-octahydro-6-(tertbutyldimethylsiloxy)-3,5,7-trimethylnaphthalen-4-yl)acrylic acid
  参考文献：
  名称：

  Total Synthesis of AMF-26, an Antitumor Agent for Inhibition of the Golgi System, Targeting ADP-Ribosylation Factor 1

  摘要：

  An effective method for the total synthesis of 1 (AMF-26), a potentially promising new anticancer drug that disrupts the Golgi system by inhibiting the ADP-ribosylation factor 1 (Arf1) activation, has been developed for the first time. The construction of the chiral linear precursor (a key to the synthesis) was achieved by the asymmetric aldol reaction followed by the computer-assisted predictive stereoselective intramolecular Diels-Alder reaction. The global antitumor activity of the totally synthetic 1 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR39), and it was shown that the synthetic 1 strongly inhibited the growth of several cancer cell lines at concentrations of less than 0.04 mu M. Biological assays of novel derivatives, 26 and 31, which have different side-chains at the C-4 positions in the Delta(1,2)-octalin backbone, disclosed the importance of the suitable structure of the side-chain containing conjugated multidouble bonds.

  DOI：

  10.1021/jm301695c

文献信息

• Total Synthesis of AMF-26, an Antitumor Agent for Inhibition of the Golgi System, Targeting ADP-Ribosylation Factor 1
  作者：Isamu Shiina、Yuma Umezaki、Yoshimi Ohashi、Yuta Yamazaki、Shingo Dan、Takao Yamori

  DOI：10.1021/jm301695c

  日期：2013.1.10

  An effective method for the total synthesis of 1 (AMF-26), a potentially promising new anticancer drug that disrupts the Golgi system by inhibiting the ADP-ribosylation factor 1 (Arf1) activation, has been developed for the first time. The construction of the chiral linear precursor (a key to the synthesis) was achieved by the asymmetric aldol reaction followed by the computer-assisted predictive stereoselective intramolecular Diels-Alder reaction. The global antitumor activity of the totally synthetic 1 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR39), and it was shown that the synthetic 1 strongly inhibited the growth of several cancer cell lines at concentrations of less than 0.04 mu M. Biological assays of novel derivatives, 26 and 31, which have different side-chains at the C-4 positions in the Delta(1,2)-octalin backbone, disclosed the importance of the suitable structure of the side-chain containing conjugated multidouble bonds.