2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran | 910095-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran
• 英文别名: hepta-5,6-dien-1-ol tetrahydropyranyl ether
• CAS: 910095-87-3
• 化学式: C₁₂H₂₀O₂
• 分子量: 196.29
• InChiKey: HNPNHFNGWZOURQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran 在 氢气 甲醇 作用下， 生成 庚-5,6-二烯-1-醇
  参考文献：
  名称：

  制备d'α-链烯基-2四氢吡喃并环化d'醇δ-链烯。

  摘要：

  DOI：

  10.1016/s0040-4039(00)85594-x
• 作为产物：
  描述：

  tetrahydropyrannyloxy-1 heptyne-6 ol-5 在 吡啶 、 lithium dimethylcuprate 、 水 作用下， 生成 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran
  参考文献：
  名称：

  制备d'α-链烯基-2四氢吡喃并环化d'醇δ-链烯。

  摘要：

  DOI：

  10.1016/s0040-4039(00)85594-x

文献信息

• Catalytic cyclometallation in steroid chemistry VI: Targeted synthesis of hybrid molecules based on steroids and tetradeca-5Z,9Z-diene-1,14-dicarboxylic acid and study of their antitumor activity
  作者：Vladimir A. D'yakonov、Regina A. Tuktarova、Lilya U. Dzhemileva、Svetlana R. Ishmukhametova、Milyausha M. Yunusbaeva、Usein M. Dzhemilev

  DOI：10.1016/j.steroids.2018.06.004

  日期：2018.10

  Hybrid molecules based on a number of steroids (cholesterol, pregnenolone, androsterone) and 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid linked via mono- and diethylene glycol spacers were synthesized for the first time and studied for antitumor activity in vitro. The acid was prepared using catalytic cyclomagnesiation of oxygenated 1,2-dienes with Grignard reagent in the presence of Cp2TiCl2 as the

  首次合成了基于多种类固醇（胆固醇，孕烯醇酮和雄甾酮）和通过单乙二醇和二甘醇间隔基连接的1,14-十四碳-5Z，9Z-二烯二羧酸的杂合分子，并在体外研究了其抗肿瘤活性。在关键的合成步骤中，在Cp2TiCl2的存在下，使用Grignard试剂对氧化的1,2-二烯进行催化环氧化，制备了酸。使用流式细胞仪，新分子首次显示出在HeLa，Hek293，U937，Jurkat和K562细胞培养物中是有效的凋亡诱导剂，并且对细胞周期的S和G2期具有剂量依赖性。
• Synthesis and transformations of metallacycles. 45. Cross-cyclomagnesiation of 1,2-dienes in the synthesis of 5Z,9Z-dienoic acids, efficient inhibitors of human topoisomerase I
  作者：V. A. D’yakonov、L. U. Dzhemileva、A. A. Makarov、A. R. Mulyukova、R. A. Tuktarova、I. I. Islamov、U. M. Dzhemilev

  DOI：10.1007/s11172-015-1128-7

  日期：2015.9

  An original method for the synthesis of natural and synthetic 5Z,9Z-dienoic acids with high selectivity (>98%) and ~50% yields was elaborated. The method is based on a new Cp2TiCl2catalyzed cross-cyclomagnesiation reaction of terminal aliphatic and O-containing 1,2-dienes using Grignard reagents. The synthesized acids exhibited in vitro high inhibiting activity against human topoisomerase I.

  详细阐述了一种以高选择性 (>98%) 和 ~50% 产率合成天然和合成 5Z,9Z-二烯酸的原始方法。该方法基于使用格氏试剂对末端脂肪族和含 O 的 1,2-二烯进行新的 Cp2TiCl2 催化交叉环镁化反应。合成的酸在体外对人拓扑异构酶 I 表现出高抑制活性。
• Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5Z,9Z)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units
  作者：Vladimir A. D’yakonov、Regina A. Tuktarova、Lilya U. Dzhemileva、Svetlana R. Ishmukhametova、Usein M. Dzhemilev

  DOI：10.3390/ph14020084

  日期：——

  For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)-1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2–4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.

  首次，基于麻黄酸和(5Z,9Z)-1,14-十四碳-5,9-二烯二羧酸，在两个阶段使用2-(庚-5,6-二烯-1-氧基)四氢-2H-吡喃的同环合镁反应合成了杂化分子。含有5Z,9Z-二烯酸的这些杂化分子作为新型合成生物活性前体，对于开发治疗人类肿瘤疾病的现代药物具有重要意义。合成的杂化分子显示出极高的体外抑制人类拓扑异构酶I活性，比已知的拓扑异构酶I抑制剂喜树碱高2-4倍。首次利用流式细胞术和荧光显微镜观察到这些新分子在HeLa、U937、Jurkat、K562和Hek293细胞培养中是有效的凋亡诱导剂。此外，还介绍了对合成酸对线粒体的影响以及对Jurkat肿瘤细胞可能的DNA损伤研究的结果。
• Natural Trienoic Acids as Anticancer Agents: First Stereoselective Synthesis, Cell Cycle Analysis, Induction of Apoptosis, Cell Signaling and Mitochondrial Targeting Studies
  作者：Vladimir A. D’yakonov、Alexey A. Makarov、Lilya U. Dzhemileva、Ilfir R. Ramazanov、Elina Kh. Makarova、Usein M. Dzhemilev

  DOI：10.3390/cancers13081808

  日期：——

  The first Z-stereoselective method was developed for the synthesis of unsaturated acids containing a 1Z,5Z,9Z-triene moiety in 61–64% yields using the new Ti-catalyzed cross-coupling of oxygen-containing and aliphatic 1,2-dienes as the key synthetic step. It was shown for the first time that trienoic acids with non-methylene-interrupted Z-double bonds show moderate cytotoxic activities against tumor cell lines (Jurkat, K562, U937, HL60, HeLa), human embryonic kidney cells (Hek293), normal fibroblasts and human topoisomerase I (hTop1) inhibitory activity in vitro. The synthesized acids efficiently initiate apoptosis of Jurkat tumor cells, with the cell death mechanism being activated by the mitochondrial pathway. A probable mechanism of topoisomerase I inhibition was also hypothesized on the basis of in silico studies resorting to docking. The activation and inhibition of the most versatile intracellular signaling pathways (CREB, JNK, NFkB, p38, ERK1/2, Akt, p70S6K, STAT3 and STAT5 tyrosine kinases) responsible for cell proliferation and for initiation of apoptosis were studied by multiplex assay technology (Luminex xMAP).

  第一个Z-立体选择性方法是为合成含有1Z,5Z,9Z-三烯基团的不饱和酸而开发的，利用新的钛催化的含氧和脂肪族1,2-二烯烃的交叉偶联作为关键合成步骤，产率为61-64%。首次表明，具有非亚甲基间断Z-双键的三烯酸对肿瘤细胞系（Jurkat，K562，U937，HL60，HeLa），人类胚胎肾细胞（Hek293），正常成纤维细胞和体外人类拓扑异构酶I（hTop1）具有中等细胞毒活性。合成的酸有效地启动Jurkat肿瘤细胞的凋亡，细胞死亡机制通过线粒体途径被激活。还根据基于对接的体外研究假设了拓扑异构酶I抑制的可能机制。通过多重分析技术（Luminex xMAP）研究了对细胞增殖和凋亡启动负责的最多功能细胞内信号通路（CREB，JNK，NFkB，p38，ERK1/2，Akt，p70S6K，STAT3和STAT5酪氨酸激酶）的激活和抑制。
• Novel organomagnesium reagents in synthesis. Catalytic cyclomagnesiation of allenes in the synthesis of N-, O-, and Si-substituted 1Z,5Z-dienes
  作者：Vladimir A. D'yakonov、Aleksey A. Makarov、Elina Kh. Makarova、Usein M. Dzhemilev

  DOI：10.1016/j.tet.2013.06.106

  日期：2013.9

  An efficient method for the synthesis of valuable N-, O-, and Si-containing 1Z,5Z-diene compounds was developed. The method comprises Cp2TiCl2-catalyzed homo- and cross-cyclomagnesiation of 1,2-dienes by Grignard reagents (RMgR′) to give 2,5-dialkylidenemagnesacyclopentanes in up to 96% yield. This approach was successfully used in the synthesis of 5Z,9Z-dienoic acids, precursors of acetogenins and

  开发了一种有效的合成有价值的含N-，O-和Si的1 Z，5 Z-二烯化合物的方法。该方法包括通过格氏试剂（RMgR'）的Cp 2 TiCl 2催化的1,2-二烯的同环和交叉环化，以高达96％的收率得到2,5-二亚烷基亚磁环环戊烷。该方法已成功用于5 Z，9 Z-二烯酸，产乙酸原素和昆虫信息素的合成。