2,8,10-O-trideacylthapsigargin | 157160-57-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,8,10-O-trideacylthapsigargin
• 英文别名: [(3S,3aR,4S,6S,6aR,7S,8S,9bS)-3,3a,6-trihydroxy-3,6,9-trimethyl-8-[(Z)-2-methylbut-2-enoyl]oxy-7-octanoyloxy-2-oxo-4,5,6a,7,8,9b-hexahydroazuleno[4,5-b]furan-4-yl] octanoate
• CAS: 157160-57-1
• 化学式: C₃₆H₅₆O₁₁
• 分子量: 664.834
• InChiKey: JKVFSBVRCRYJAF-VXSRQGSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  47
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2,8,10-O-trideacylthapsigargin 在 锂硼氢 作用下， 以 甲苯 为溶剂， 反应 0.1h， 以17.7%的产率得到2,8-O-dioctanoyl-2,8,10-O-trideacylthapsigargin lactone
  参考文献：
  名称：

  Structure-Activity Relationships of Analogs of Thapsigargin Modified at O-11 and O-12

  摘要：

  A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca2+-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.

  DOI：

  10.1021/jm00002a009
• 作为产物：
  描述：

  毒胡萝卜素 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 49.0h， 生成 2,8,10-O-trideacylthapsigargin
  参考文献：
  名称：

  Andersen, Annette; Cornett, Claus; Lauridsen, Annette, Acta Chemica Scandinavica, 1994, vol. 48, # 4, p. 340 - 346

  摘要：

  DOI：

文献信息

• Elucidation of the topography of the thapsigargin binding site in the sarco-endoplasmic calcium ATPase
  作者：Dorthe Mondrup Skytte、Jesper Vuust Møller、Huizhen Liu、Helle Østergren Nielsen、Louise Elsa Svenningsen、Christina Mernøe Jensen、Carl Erik Olsen、Søren Brøgger Christensen

  DOI：10.1016/j.bmc.2010.06.032

  日期：2010.8

  Removal of each of the acyl groups of thapsigargin at O-3, O-8 and O-10 significant reduces the affinity of the inhibitors to the SERCA1a pump. Replacement of the acyl groups at O-3 and O-10 with flexible residues could be performed with only a minor decrease of the affinity, whereas introduction of voluminous stiff residues caused dramatic reduction of the affinity. The results can be rationalized on the basis of the interactions of thapsigargin with the SERCA1a pump as revealed from 3D X-ray structural models of thapsigargin bound to the SERCA1a. In conclusion the results confirm and elaborate the previously suggested pharmocophore model of thapsigargin. (C) 2010 Elsevier Ltd. All rights reserved.
• Andersen, Annette; Cornett, Claus; Lauridsen, Annette, Acta Chemica Scandinavica, 1994, vol. 48, # 4, p. 340 - 346
  作者：Andersen, Annette、Cornett, Claus、Lauridsen, Annette、Olsen, Carl E.、Christensen, Soeren Broegger

  DOI：——

  日期：——
• Structure-Activity Relationships of Analogs of Thapsigargin Modified at O-11 and O-12
  作者：Simon Feldbk Nielsen、Ole Thastrup、Rudi Pedersen、Carl Erik Olsen、Soren Brogger Christensen

  DOI：10.1021/jm00002a009

  日期：1995.1

  A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca2+-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.