(2R,4R,6R,8R)-8-allyl-2-(4-(3-(benzyloxy)phenyl)butyl)-11,11-dimethyl-1,7-dioxaspiro[5.5]undecan-4-ol | 1160697-52-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2R,4R,6R,8R)-8-allyl-2-(4-(3-(benzyloxy)phenyl)butyl)-11,11-dimethyl-1,7-dioxaspiro[5.5]undecan-4-ol
• CAS: 1160697-52-8
• 化学式: C₃₁H₄₂O₄
• 分子量: 478.672
• InChiKey: NLAHBXHFRAPFJV-LBWLPYLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.0
• 重原子数：
  35.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  47.92
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2R,4R,6R,8R)-8-allyl-2-(4-(3-(benzyloxy)phenyl)butyl)-11,11-dimethyl-1,7-dioxaspiro[5.5]undecan-4-ol 、 在 2,4,6-三氯苯甲酰氯 、 三乙胺 、 4-二甲氨基吡啶 作用下， 以 甲苯 为溶剂， 反应 4.5h， 以100%的产率得到
  参考文献：
  名称：

  Structure–activity studies at position 27 of aplog-1, a simplified analog of debromoaplysiatoxin with anti-proliferative activity

  摘要：

  Aplog-1, a simplified analog of debromoaplysiatoxin with anti-proliferative activity, bound to and activated protein kinase delta (PKC delta), that is involved in tumor suppression and apoptosis. To examine the contribution of PKC delta to the anti-proliferative activity of aplog-1, we synthesized 27-methyl and 27-methoxy derivatives that differed in the ability to activate PKC delta. Activators of PKC delta like aplog-1 and 27-(R)-Me-aplog-1 strongly inhibited the growth of several cancer cell lines. On the other hand, 27-(S)-Me-aplog-1 and 27-O-Me-aplog-1 without the ability to activate PKC delta, exhibited only weak growth inhibitory activity against these cell lines. These results suggest indirectly that the activation of PKC delta might be involved in the anti-proliferative activity of aplog-1 against aplog-sensitive cancer cell lines. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.02.008
• 作为产物：
  描述：

  在 4-甲基苯磺酸吡啶 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 以35%的产率得到(2R,4R,6R,8R)-8-allyl-2-(4-(3-(benzyloxy)phenyl)butyl)-11,11-dimethyl-1,7-dioxaspiro[5.5]undecan-4-ol
  参考文献：
  名称：

  Nakagawa, Yu; Yanagita, Ryo C.; Hamada, Naoko, Journal of the American Chemical Society, 2009, vol. 131, p. 7573 - 7579

  摘要：

  DOI：

文献信息

• Synthesis and biological activities of the amide derivative of aplog-1, a simplified analog of aplysiatoxin with anti-proliferative and cytotoxic activities
  作者：Yusuke Hanaki、Ryo C Yanagita、Takahiro Sugahara、Misako Aida、Harukuni Tokuda、Nobutaka Suzuki、Kazuhiro Irie

  DOI：10.1080/09168451.2014.1002452

  日期：2015.6.3

  negligible anti-proliferative and cytotoxic activities even at 10(-4) M. A conformational analysis and density functional theory calculations indicated that the stable conformation of 3 differed from that of aplog-1. Since 27-methyl and 27-methoxy derivatives (1, 2) without the ability to bind to PKC isozymes exhibited marked anti-proliferative and cytotoxic activities at 10(-4) M, 3 may be an inactive control

  Aplog-1是促进肿瘤的aplysiatoxin的简化类似物，具有针对几种癌细胞系的抗增殖和细胞毒性活性。我们最近的发现表明蛋白激酶Cδ（PKCδ）可能是aplog-1的目标蛋白之一。在这项研究中，我们合成了酰胺-aplog-1（3），其中C-1酯基被酰胺基取代，以提高体内化学稳定性。不幸的是，3在PKCδ的C1B结构域上的结合亲和力比aplog-1弱70倍，即使在10（-4）M时抗增殖和细胞毒性活性也微不足道。构象分析和密度泛函理论计算表明3的稳定构象与aplog-1的构象不同。由于27-甲基和27-甲氧基衍生物（1，