dolastatin 11 | 860802-17-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: dolastatin 11
• CAS: 860802-17-1
• 化学式: C₅₀H₈₀N₈O₁₂
• 分子量: 985.232
• InChiKey: XOSLDLHSPLPVME-GUKRYUKPSA-N

反应信息

• 作为反应物：
  描述：

  dolastatin 11 在 吡啶 、 sodium tetrahydroborate 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 16.25h， 生成 Acetic acid (2S,8S,14S,17S,20S,21R,25R,28R,29R)-2-((S)-sec-butyl)-28-ethyl-8-isobutyl-14-isopropyl-17-(4-methoxy-benzyl)-7,13,16,20,22,22,25,29-octamethyl-3,6,9,12,15,18,23,26,30-nonaoxo-1-oxa-4,7,10,13,16,19,24,27-octaaza-cyclotriacont-21-yl ester
  参考文献：
  名称：

  Dolastatin 11 conformations, analogues and pharmacophore

  摘要：

  Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin I I is a candidate for conversion to prodrugs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.040
• 作为产物：
  描述：

  在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以44%的产率得到dolastatin 11
  参考文献：
  名称：

  Dolastatin 11 conformations, analogues and pharmacophore

  摘要：

  Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin I I is a candidate for conversion to prodrugs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.040