debromo aplysiatoxin | 52423-28-6

• 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: debromo aplysiatoxin
• 英文别名: debromoaplysiatoxin；DAT；(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S,5S)-5-(3-hydroxyphenyl)-5-methoxypentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione
• CAS: 52423-28-6
• 化学式: C₃₂H₄₈O₁₀
• 分子量: 592.727
• InChiKey: REAZZDPREXHWNV-HJUJCDCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  debromo aplysiatoxin 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 (4R,5R)-4,5-dihydro-4-hydroxy-5-methyl-2(3H)-furanone
  参考文献：
  名称：

  Absolute stereochemistries of the aplysiatoxins and oscillatoxin A

  摘要：

  DOI：

  10.1021/jo00187a035
• 作为产物：
  描述：

  (1S,3R,4S,5S,9R,13S,14R)-9-((R)-1-Benzyloxymethoxy-ethyl)-3-[(1S,4S)-4-(3-benzyloxymethoxy-phenyl)-4-methoxy-1-methyl-butyl]-13-hydroxy-4,14,16,16-tetramethyl-2,6,10,17-tetraoxa-tricyclo[11.3.1.1^1,5]octadecane-7,11-dione 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 以61%的产率得到debromo aplysiatoxin
  参考文献：
  名称：

  Total synthesis of debromoaplysiatoxin and aplysiatoxin

  摘要：

  DOI：

  10.1021/ja00254a062

文献信息

• Manauealide C and Anhydrodebromoaplysiatoxin, Toxic Constituents of the Hawaiian Red Alga,<i>Gracilaria coronopifolia</i>
  作者：Hiroshi NAGAI、Yukiko KAN、Tsuyoshi FUJITA、Bryan SAKAMOTO、Yoshitsugi HOKAMA

  DOI：10.1271/bbb.62.1011

  日期：1998.1

  Manauealide C (1) and anhydrodebromoaplysiatoxin (4), toxic constituents of the Hawaiian red alga, Gracilaria coronopifolia which has been concerned with food poisoning cases, were studied. The absolute structure of manauealide C was determined as 1 by chemical conversion and spectroscopic methods. The first complete assignment of 13C chemical shifts for anhydrodebromoaplysiatoxin (4) was established. The biological activity of 4 was also investigated.

  研究了夏威夷红藻（Gracilaria coronopifolia）的两种有毒成分——马努埃利德C（1）和脱水脱溴阿普利西亚毒素（4），这两种成分与食物中毒事件有关。通过化学转换和光谱分析法，确定了马努埃利德C的绝对结构为1。首次完整确定了脱水脱溴阿普利西亚毒素（4）的13C化学位移。还研究了4的生物活性。
• JP6170908
  申请人：——

  公开号：——

  公开（公告）日：——
• Effects of the methoxy group in the side chain of debromoaplysiatoxin on its tumor-promoting and anti-proliferative activities
  作者：Ryo C. Yanagita、Hiroaki Kamachi、Masayuki Kikumori、Harukuni Tokuda、Nobutaka Suzuki、Kiyotake Suenaga、Hiroshi Nagai、Kazuhiro Irie

  DOI：10.1016/j.bmcl.2013.05.096

  日期：2013.8

  Debromoaplysiatoxin (DAT) is a tumor promoter isolated from sea hare and exhibits anti-proliferative activity against several cancer cell lines. To clarify key residues that are responsible for its tumor-promoting activity, we focused on the chiral methoxy group in the side chain, whose role had not yet been discussed or examined before. Demethoxy-DAT (8) was derived from DAT and we evaluated its tumor-promoting activity, anti-proliferative activity, and ability to bind to protein kinase C (PKC) isozymes. Compound 8 showed somewhat weaker tumor-promoting activity than that of DAT both in vitro and in vivo, but showed higher anti-proliferative activity against several cancer cell lines. Although the affinity to novel PKC isozymes of 8 was comparable to that of DAT, the affinity to conventional PKC isozymes decreased slightly. These results suggest that the methoxy group of DAT is one of the key residues critical for tumor-promoting activity but not for anti-proliferative activity. Since the methoxy group has little influence on the molecular hydrophobicity, this is the first report showing that structural factors other than hydrophobicity in the side chain of DAT affected its biological activities. (C) 2013 Elsevier Ltd. All rights reserved.
• [EN] COMPOUNDS FOR USE IN ANTI-CANCER IMMUNOTHERAPY<br/>[FR] COMPOSÉS DESTINÉS À ÊTRE UTILISÉS EN IMMUNOTHÉRAPIE ANTICANCÉREUSE
  申请人：SIRENAS LLC

  公开号：WO2020243359A1

  公开（公告）日：2020-12-03

  The present disclosure relates to the reversal of T cell exhaustion using aplysiatoxin analogs or PKC theta agonist compounds for anti-cancer immunotherapy. The treatment with aplysiatoxin analogs or PKC theta agonist compounds improve the anti-tumour activity of a T cell, inducing a NFAT-dependent T cell activation, increasing the pool of immune-checkpoint inhibitor responsive T cells, increasing lymphocyte infiltration and increasing the population of activated CD4+ and/or CD8+ cells. The methods of the present disclosure provide treatment of tumors and infections.
• Total synthesis of debromoaplysiatoxin and aplysiatoxin
  作者：Pyeong Uk Park、Chris A. Broka、Bruce F. Johnson、Yoshito Kishi

  DOI：10.1021/ja00254a062

  日期：1987.9