[(1S,5S,6R,7S,8S,10S,11S,13R,16S)-13-acetyloxy-7-hydroxy-8-iodo-7-(iodomethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-triethylsilyloxy-2,4-dioxatetracyclo[12.3.1.01,5.06,11]octadec-14-en-16-yl] (2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoate | 670220-82-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(1S,5S,6R,7S,8S,10S,11S,13R,16S)-13-acetyloxy-7-hydroxy-8-iodo-7-(iodomethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-triethylsilyloxy-2,4-dioxatetracyclo[12.3.1.01,5.06,11]octadec-14-en-16-yl] (2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoate
• CAS: 670220-82-3
• 化学式: C₅₁H₇₁I₂NO₁₂Si₂
• 分子量: 1200.1
• InChiKey: TUKPKIKCGKHPCC-FGIUAKRISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.38
• 重原子数：
  68
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [(1S,5S,6R,7S,8S,10S,11S,13R,16S)-13-acetyloxy-7-hydroxy-8-iodo-7-(iodomethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-triethylsilyloxy-2,4-dioxatetracyclo[12.3.1.01,5.06,11]octadec-14-en-16-yl] (2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoate 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 lithium chloride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 [(1S,5S,6R,7S,10S,11S,13R,16S)-13-acetyloxy-7-hydroxy-7,11,15,18,18-pentamethyl-3,12-dioxo-10-triethylsilyloxy-2,4-dioxatetracyclo[12.3.1.01,5.06,11]octadeca-8,14-dien-16-yl] (2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoate
  参考文献：
  名称：

  Restoration of Microtubule Interaction and Cytotoxicity in D-seco Taxanes upon Incorporation of 20-Hydroxymethyl-4-allyloxy Groups

  摘要：

  To probe the exact role of the oxetane D ring in both tubulin binding and cytotoxicity of taxanes, novel D-seco taxanes bearing a C4 ether substituent have been prepared from paclitaxel 1a. Among them, 20-hydroxymethyl-4-allyloxy D-seco taxane 5e is the most active in both tubulin and cytotoxicity assays. It is only slightly less potent than 1a on tubulin polymerization promotion in vitro and the most cytotoxic among all D-seco taxanes known to date. The reason for the loss and restoration of bioactivity for these D-seco taxanes is also discussed with the assistance of NMR and molecular modeling studies. From these results, we draw a conclusion that the intact D ring of taxanes is not strictly necessary for their binding to tubulin and cytotoxic effects.

  DOI：

  10.1021/acs.orglett.5b03119
• 作为产物：
  描述：

  2'-(tert-butyldimethylsilyl)-2-debenzoyl-4-deacetyl-7-(triethylsilyl)-5-α-iodo-20-hydroxy-D-seco-paclitaxel 1,2-carbonate 在 4-二甲氨基吡啶 、 三氟甲烷磺酰氯 、 三氟化硼乙醚 、 四丁基碘化铵 作用下， 以 二氯甲烷 为溶剂， 生成 [(1S,5S,6R,7S,8S,10S,11S,13R,16S)-13-acetyloxy-7-hydroxy-8-iodo-7-(iodomethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-triethylsilyloxy-2,4-dioxatetracyclo[12.3.1.01,5.06,11]octadec-14-en-16-yl] (2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoate
  参考文献：
  名称：

  Restoration of Microtubule Interaction and Cytotoxicity in D-seco Taxanes upon Incorporation of 20-Hydroxymethyl-4-allyloxy Groups

  摘要：

  To probe the exact role of the oxetane D ring in both tubulin binding and cytotoxicity of taxanes, novel D-seco taxanes bearing a C4 ether substituent have been prepared from paclitaxel 1a. Among them, 20-hydroxymethyl-4-allyloxy D-seco taxane 5e is the most active in both tubulin and cytotoxicity assays. It is only slightly less potent than 1a on tubulin polymerization promotion in vitro and the most cytotoxic among all D-seco taxanes known to date. The reason for the loss and restoration of bioactivity for these D-seco taxanes is also discussed with the assistance of NMR and molecular modeling studies. From these results, we draw a conclusion that the intact D ring of taxanes is not strictly necessary for their binding to tubulin and cytotoxic effects.

  DOI：

  10.1021/acs.orglett.5b03119

文献信息

• Synthesis, Modeling, and Anti-Tubulin Activity of a D-Seco Paclitaxel Analogue
  作者：Luciano Barboni、Guido Giarlo、Massimo Ricciutelli、Roberto Ballini、Gunda I. Georg、David G. VanderVelde、Richard H. Himes、Minmin Wang、Ami Lakdawala、James P. Snyder

  DOI：10.1021/ol036204c

  日期：2004.2.1

  We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.