(1S,3R,5R,9R,13R)-3-[4-(2-bromo-5-hydroxyphenyl)butyl]-9-(hydroxymethyl)-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione | 1431705-78-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (1S,3R,5R,9R,13R)-3-[4-(2-bromo-5-hydroxyphenyl)butyl]-9-(hydroxymethyl)-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione
• CAS: 1431705-78-0
• 化学式: C₂₇H₃₇BrO₈
• 分子量: 569.49
• InChiKey: XAVHENBENCIKCO-DAACTFMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  aplysiatoxin 在 benzyltrimethylammonium tribromide 、 calcium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以68%的产率得到(1S,3R,5R,9R,13R)-3-[4-(2-bromo-5-hydroxyphenyl)butyl]-9-(hydroxymethyl)-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione
  参考文献：
  名称：

  Structure–activity studies on the side chain of a simplified analog of aplysiatoxin (aplog-1) with anti-proliferative activity

  摘要：

  We have recently developed a simplified analog of aplysiatoxin (aplog-1) as an activator of protein kinase C (PKC) with anti-proliferative activity like bryostain 1. To identify sites in aplog-1 that could be readily modified to optimize therapeutic performance and to develop a molecular probe for examining the analog's mode of action, substituent effects on the phenol ring were systematically examined. Whereas hydrophilic acetamido derivatives were less active than aplog-1 in inhibiting cancer cell growth and binding to PKCS, introduction of hydrophobic bromine and iodine atoms enhanced both biological activities. The anti-proliferative activity was found to correlate closely with molecular hydrophobicity, and maximal activity was observed at a log P value of 4.0-4.5. On the other hand, an induction test with Epstein-Barr virus early antigen demonstrated that these derivatives have less tumor-promoting activity in vitro than aplog-1 regardless of the hydrophobicity of their substituents. These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.013

文献信息

• Structure–activity studies on the side chain of a simplified analog of aplysiatoxin (aplog-1) with anti-proliferative activity
  作者：Hiroaki Kamachi、Keisuke Tanaka、Ryo C. Yanagita、Akira Murakami、Kazuma Murakami、Harukuni Tokuda、Nobutaka Suzuki、Yu Nakagawa、Kazuhiro Irie

  DOI：10.1016/j.bmc.2013.03.013

  日期：2013.5

  We have recently developed a simplified analog of aplysiatoxin (aplog-1) as an activator of protein kinase C (PKC) with anti-proliferative activity like bryostain 1. To identify sites in aplog-1 that could be readily modified to optimize therapeutic performance and to develop a molecular probe for examining the analog's mode of action, substituent effects on the phenol ring were systematically examined. Whereas hydrophilic acetamido derivatives were less active than aplog-1 in inhibiting cancer cell growth and binding to PKCS, introduction of hydrophobic bromine and iodine atoms enhanced both biological activities. The anti-proliferative activity was found to correlate closely with molecular hydrophobicity, and maximal activity was observed at a log P value of 4.0-4.5. On the other hand, an induction test with Epstein-Barr virus early antigen demonstrated that these derivatives have less tumor-promoting activity in vitro than aplog-1 regardless of the hydrophobicity of their substituents. These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1. (C) 2013 Elsevier Ltd. All rights reserved.