1-((1R,2R,5S)-2-(4-chlorobenzyl)-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]oct-2-yl)ethanone

• 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: 1-((1R,2R,5S)-2-(4-chlorobenzyl)-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]oct-2-yl)ethanone
• 英文别名: 1-[(1r,2r,5s)-2-(4-Chlorobenzyl)-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone；1-[(1R,2R,5S)-2-[(4-chlorophenyl)methyl]-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone
• 化学式: C₁₆H₁₉ClO₄
• 分子量: 310.777
• InChiKey: REWQPRYLLIBCAN-ARFHVFGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((1R,2R,5S)-2-(4-chlorobenzyl)-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]oct-2-yl)ethanone 、 β-cyclodextrin 以 水 、 乙腈 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Elucidation of the in vitro and in vivo activities of bridged 1,2,4-trioxolanes, bridged 1,2,4,5-tetraoxanes, tricyclic monoperoxides, silyl peroxides, and hydroxylamine derivatives against Schistosoma mansoni

  摘要：

  Praziquantel is currently the only drug available to treat schistosomiasis. Since drug resistance would be a major barrier for the increasing global attempts to eliminate schistosomiasis as a public health problem, efforts should go hand in hand with the discovery of novel treatment options. Synthetic peroxides might offer a good direction since their antischistosomal activity has been demonstrated in the laboratory. We studied 19 bridged 1,2,4,5-tetraoxanes, 2 tricyclic monoperoxides, 11 bridged 1,2,4-trioxolanes, 12 silyl peroxides, and 4 hydroxylamine derivatives against newly transformed schistosomula (NTS) and adult Schistosoma mansoni in vitro. Schistosomicidal compounds were tested for cytotoxicity followed by in vivo studies of the most promising compounds. Tricyclic monoperoxides, trioxolanes, and tetraoxanes revealed the highest in vitro activity against NTS (IC(50)s 0.4-20.2 mu M) and adult schistosomes (IC(50)s 1.8-22.8 mu M). Tetraoxanes showed higher cytotoxicity than antischistosomal activity. Selected trioxolane and tricyclic monoperoxides were tested in mice harboring an adult S. mansoni infection. The highest activity was observed for two trioxolanes, which showed moderate worm burden reductions (WBR) of 44.3% and 42.9% (p > 0.05). Complexation of the compounds with beta-cyclodextrin with the aim to improve solubility and gastrointestinal absorption did not increase in vivo antischistosomal efficacy. The high in vitro antischistosomal activity of trioxolanes and tricyclic monoperoxides is a promising basis for future investigations, with the focus on improving in vivo efficacy. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.010
• 作为产物：
  描述：

  3-[(4-氯苯基)甲基]戊烷-2,4-二酮 在 phosphomolybdic acid 、 双氧水 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 8.0h， 生成 1-((1R,2R,5S)-2-(4-chlorobenzyl)-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]oct-2-yl)ethanone 、 1-((1R,2S,5S)-2-(4-chlorobenzyl)-1,5-dimethyl-6,7,8-trioxabicyclo[3.2.1]oct-2-yl)ethanone
  参考文献：
  名称：

  环过氧化物作为有希望的抗癌药：合成的臭氧化物和四恶烷对人前列腺癌细胞系的体外细胞毒性研究

  摘要：

  摘要当在不依赖雄激素的前列腺癌细胞系DU145和PC3上进行测试时，合成的臭氧化物和四恶烷在体外具有很高的细胞毒性，在某些情况下高于阿霉素，顺铂，依托泊苷，青蒿素和青蒿琥酯。臭氧化物立体异构体的活性彼此不同。活性的这种差异以及立体异构体的活性与其氧化性质之间不存在相关性，这使我们提出了这些内过氧化物的细胞毒性的非常特定的机制，与主要基于过氧化物的氧化性质的传统机制不同。 图形概要

  DOI：

  10.1007/s00044-016-1736-2

文献信息

• Synthesis of peroxides from β,δ-triketones under heterogeneous conditions
  作者：A. O. Terent’ev、I. A. Yaremenko、A. P. Glinushkin、G. I. Nikishin

  DOI：10.1134/s1070428015120027

  日期：2015.12

  Heterogeneous reactions of beta,delta-triketones with ethereal hydrogen peroxide in nonpolar solvents, catalyzed by phosphomolybdic acid, afforded mixtures of stereoisomeric ozonides, tricyclic monoperoxides, and bridged tetraoxanes. The trioxolane ring is formed by the carbonyl groups located in the delta-position with respect to each other.
• Cyclic peroxides as promising anticancer agents: in vitro cytotoxicity study of synthetic ozonides and tetraoxanes on human prostate cancer cell lines
  作者：Ivan A. Yaremenko、Mikhail A. Syroeshkin、Dmitri O. Levitsky、Fabrice Fleury、Alexander O. Terent’ev

  DOI：10.1007/s00044-016-1736-2

  日期：2017.1

  AbstractSynthetic ozonides and tetraoxanes were shown to have high cytotoxicity in vitro when tested on androgen-independent prostate cancer cell lines DU145 and PC3, which is in some cases was higher than that of doxorubicin, cisplatin, etoposide, artemisinin, and artesunate. Activity of ozonide stereoisomers differs from each other. This difference in activity and absence of correlation between activity

  摘要当在不依赖雄激素的前列腺癌细胞系DU145和PC3上进行测试时，合成的臭氧化物和四恶烷在体外具有很高的细胞毒性，在某些情况下高于阿霉素，顺铂，依托泊苷，青蒿素和青蒿琥酯。臭氧化物立体异构体的活性彼此不同。活性的这种差异以及立体异构体的活性与其氧化性质之间不存在相关性，这使我们提出了这些内过氧化物的细胞毒性的非常特定的机制，与主要基于过氧化物的氧化性质的传统机制不同。 图形概要
• Elucidation of the in vitro and in vivo activities of bridged 1,2,4-trioxolanes, bridged 1,2,4,5-tetraoxanes, tricyclic monoperoxides, silyl peroxides, and hydroxylamine derivatives against Schistosoma mansoni
  作者：Noemi Cowan、Ivan A. Yaremenko、Igor B. Krylov、Alexander O. Terent’ev、Jennifer Keiser

  DOI：10.1016/j.bmc.2015.02.010

  日期：2015.8

  Praziquantel is currently the only drug available to treat schistosomiasis. Since drug resistance would be a major barrier for the increasing global attempts to eliminate schistosomiasis as a public health problem, efforts should go hand in hand with the discovery of novel treatment options. Synthetic peroxides might offer a good direction since their antischistosomal activity has been demonstrated in the laboratory. We studied 19 bridged 1,2,4,5-tetraoxanes, 2 tricyclic monoperoxides, 11 bridged 1,2,4-trioxolanes, 12 silyl peroxides, and 4 hydroxylamine derivatives against newly transformed schistosomula (NTS) and adult Schistosoma mansoni in vitro. Schistosomicidal compounds were tested for cytotoxicity followed by in vivo studies of the most promising compounds. Tricyclic monoperoxides, trioxolanes, and tetraoxanes revealed the highest in vitro activity against NTS (IC(50)s 0.4-20.2 mu M) and adult schistosomes (IC(50)s 1.8-22.8 mu M). Tetraoxanes showed higher cytotoxicity than antischistosomal activity. Selected trioxolane and tricyclic monoperoxides were tested in mice harboring an adult S. mansoni infection. The highest activity was observed for two trioxolanes, which showed moderate worm burden reductions (WBR) of 44.3% and 42.9% (p > 0.05). Complexation of the compounds with beta-cyclodextrin with the aim to improve solubility and gastrointestinal absorption did not increase in vivo antischistosomal efficacy. The high in vitro antischistosomal activity of trioxolanes and tricyclic monoperoxides is a promising basis for future investigations, with the focus on improving in vivo efficacy. (C) 2015 Elsevier Ltd. All rights reserved.