aplysiatoxin | 1160697-60-8

• 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: aplysiatoxin
• 英文别名: aplog-1；(1S,3R,5R,9R,13R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione
• CAS: 1160697-60-8
• 化学式: C₂₇H₃₈O₈
• 分子量: 490.594
• InChiKey: WQEXBJWFPAMSGJ-HLGBLHBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  35
• 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

• 作为反应物：
  描述：

  aplysiatoxin 在 benzyltrimethylammonium tribromide 、 calcium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.5h， 以92%的产率得到(1S,3R,5R,9R,13R)-9-(hydroxymethyl)-16,16-dimethyl-3-[4-(2,4,6-tribromo-3-hydroxyphenyl)butyl]-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
• 作为产物：
  描述：

  (1S,3R,5R,9R,13R)-16,16-dimethyl-9-(phenylmethoxymethyl)-3-[4-(3-phenylmethoxyphenyl)butyl]-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以97%的产率得到aplysiatoxin
  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 of Antineoplastic Analogs of Aplysiatoxin with Various Side Chain Structures
  作者：Kazuhiro Irie、Ryo C. Yanagita、Harukuni Tokuda、Nobutaka Suzuki、Yuki Shu

  DOI：10.3987/com-12-s(n)8

  日期：——

  We have recently developed a simplified analog of aplysiatoxin with anti-proliferative activity (1). To investigate the structure activity relationship of its side chain, an alternative synthetic route of 1 has been established. Via the key intermediate 6, p-hydroxyl or o,m-dihydroxyl derivatives (4 and 5) as well as 1 were synthesized and their biological activities were evaluated. Although the position of the hydroxyl group in the benzene ring did not change the affinity for protein kinase C isozymes or the ability to induce the Epstein-Barr virus early antigen, anti-proliferative activities against several human cancer cell lines of 1 were superior to those of 4.
• JP6170908
  申请人：——

  公开号：——

  公开（公告）日：——
• Role of the phenolic hydroxyl group in the biological activities of simplified analogue of aplysiatoxin with antiproliferative activity
  作者：Ryo C. Yanagita、Hiroaki Kamachi、Keisuke Tanaka、Akira Murakami、Yu Nakagawa、Harukuni Tokuda、Hiroshi Nagai、Kazuhiro Irie

  DOI：10.1016/j.bmcl.2010.08.051

  日期：2010.10

  The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with antiproliferative activity was synthesized to examine the role of the phenolic hydroxyl group at position 18 in the biological activities of 1. Compound 3 as well as 1 showed significant affinity for protein kinase C delta (PKC delta), and the antiproliferative activity of 3 was slightly higher than that of 1. However, the anti-tumor-promoting activity of 3 was less than that of 1 in vitro, suggesting that the phenolic hydroxyl group of 1 is necessary for the anti-tumor-promoting activity but not for the binding of PKCd and antiproliferative activity. Moreover, PKC isozyme selectivity of 3 was similar to that of 1, suggesting non-PKC receptors for these compounds to play some roles in the anti-tumor-promoting activity of 1. (c) 2010 Elsevier Ltd. All rights reserved.
• Nakagawa, Yu; Yanagita, Ryo C.; Hamada, Naoko, Journal of the American Chemical Society, 2009, vol. 131, p. 7573 - 7579
  作者：Nakagawa, Yu、Yanagita, Ryo C.、Hamada, Naoko、Murakami, Akira、Takahashi, Hideyuki、et al.

  DOI：——

  日期：——
• 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.