(1S,3R,5R,9R,13S,14R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-14,16,16-trimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione | 1380327-86-5

• 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,13S,14R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-14,16,16-trimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione
• CAS: 1380327-86-5
• 化学式: C₂₈H₄₀O₈
• 分子量: 504.621
• InChiKey: LPMWTDXPUOFZOV-NYQPXYKCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  [(2S,3R,6S,8R,10R)-3,5,5-trimethyl-8-[4-(3-phenylmethoxyphenyl)butyl]-2-prop-2-enyl-1,7-dioxaspiro[5.5]undecan-10-yl] (3R)-3-[(4-methoxyphenyl)methoxy]-4-phenylmethoxybutanoate 在 咪唑 、 potassium permanganate 、 sodium periodate 、 2,4,6-三氯苯甲酰氯 、 20 % Pd(OH)2/C 、 水 、 氢气 、 氟化氢吡啶 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 甲苯 、 叔丁醇 为溶剂， 反应 28.33h， 生成 (1S,3R,5R,9R,13S,14R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-14,16,16-trimethyl-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 Spiroketal Moiety of a Simplified Analogue of Debromoaplysiatoxin with Antiproliferative Activity

  摘要：

  Aplog-1, a simplified analogue of tumor-promoting debromoaplysiatoxin, is antiproliferative but not tumor-promoting. Our recent study has suggested that local hydrophobicity around the spiroketal moiety is a crucial determinant for antiproliferative activity. To further clarify the structural features relevant to the activity, we synthesized two methyl derivatives of aplog-1, where a methyl group was installed at position 4 or 10 of the spiroketal moiety. 10-Methyl-aplog-1 (5) bound to the C1B domains of novel PKCs (delta, eta and theta) with subnanomolar K-i values, approximately 10-20 times stronger than aplog-1, and markedly inhibited the growth of many human cancer cell lines, while 4-methyl-aplog-1 (4) had levels of activity similar to those of aplog-1. Interestingly, 5 showed little tumor-promoting activity unlike the tumor promoter debromoaplysiatoxin. These results suggest that 5 is a potent PKC ligand without tumor-promoting activity and could be a therapeutic lead for the treatment of cancer, like bryostatins.

  DOI：

  10.1021/jm300566h

文献信息

• Structure–Activity Studies on the Spiroketal Moiety of a Simplified Analogue of Debromoaplysiatoxin with Antiproliferative Activity
  作者：Masayuki Kikumori、Ryo C. Yanagita、Harukuni Tokuda、Nobutaka Suzuki、Hiroshi Nagai、Kiyotake Suenaga、Kazuhiro Irie

  DOI：10.1021/jm300566h

  日期：2012.6.14

  Aplog-1, a simplified analogue of tumor-promoting debromoaplysiatoxin, is antiproliferative but not tumor-promoting. Our recent study has suggested that local hydrophobicity around the spiroketal moiety is a crucial determinant for antiproliferative activity. To further clarify the structural features relevant to the activity, we synthesized two methyl derivatives of aplog-1, where a methyl group was installed at position 4 or 10 of the spiroketal moiety. 10-Methyl-aplog-1 (5) bound to the C1B domains of novel PKCs (delta, eta and theta) with subnanomolar K-i values, approximately 10-20 times stronger than aplog-1, and markedly inhibited the growth of many human cancer cell lines, while 4-methyl-aplog-1 (4) had levels of activity similar to those of aplog-1. Interestingly, 5 showed little tumor-promoting activity unlike the tumor promoter debromoaplysiatoxin. These results suggest that 5 is a potent PKC ligand without tumor-promoting activity and could be a therapeutic lead for the treatment of cancer, like bryostatins.