(5R)-7-[2-[[(4R,6R)-2,2-dimethyl-6-[4-(3-phenylmethoxyphenyl)butyl]-1,3-dioxan-4-yl]methyl]-1,3-dithian-2-yl]-5,7-dimethyloct-1-en-4-ol | 1380327-94-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5R)-7-[2-[[(4R,6R)-2,2-dimethyl-6-[4-(3-phenylmethoxyphenyl)butyl]-1,3-dioxan-4-yl]methyl]-1,3-dithian-2-yl]-5,7-dimethyloct-1-en-4-ol
• CAS: 1380327-94-5
• 化学式: C₃₈H₅₆O₄S₂
• 分子量: 640.992
• InChiKey: MKLWCUAMQOXSPG-WNLDFEOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  98.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5R)-7-[2-[[(4R,6R)-2,2-dimethyl-6-[4-(3-phenylmethoxyphenyl)butyl]-1,3-dioxan-4-yl]methyl]-1,3-dithian-2-yl]-5,7-dimethyloct-1-en-4-ol 在 mercury (II) perchlorate trihydrate 、 2,4,6-三氯苯甲酰氯 、 camphor-10-sulfonic acid 、 水 、 对甲苯磺酸 、 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 、 水 、 甲苯 、 乙腈 为溶剂， 反应 8.0h， 生成 [(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-hydroxy-4-phenylmethoxybutanoate
  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
• 作为产物：
  描述：

  (2R,4R)-1-[2-[(4R)-5-hydroxy-2,4-dimethylpentan-2-yl]-1,3-dithian-2-yl]-8-(3-phenylmethoxyphenyl)octane-2,4-diol 在 四丙基高钌酸铵 、 camphor-10-sulfonic acid 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 1.25h， 生成 (5R)-7-[2-[[(4R,6R)-2,2-dimethyl-6-[4-(3-phenylmethoxyphenyl)butyl]-1,3-dioxan-4-yl]methyl]-1,3-dithian-2-yl]-5,7-dimethyloct-1-en-4-ol
  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