(-)-(2R,3R,6R,7R,10R,11R)-1,2:3,6:7,10:11,12-tetraepoxydodecane | 173427-88-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: (-)-(2R,3R,6R,7R,10R,11R)-1,2:3,6:7,10:11,12-tetraepoxydodecane
• 英文别名: (2R,5R)-2-[(2R)-oxiran-2-yl]-5-[(2R,5R)-5-[(2R)-oxiran-2-yl]oxolan-2-yl]oxolane
• CAS: 173427-88-8
• 化学式: C₁₂H₁₈O₄
• 分子量: 226.273
• InChiKey: ZKSGPFOBPASUCU-PAUJSFGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  43.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-(2R,3R,6R,7R,10R,11R)-1,2:3,6:7,10:11,12-tetraepoxydodecane 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 Wilkinson's catalyst 、 三氟化硼乙醚 、 氢气 、 potassium carbonate 、 三乙胺 、 乙酰氯 作用下， 以 甲醇 、 乙醚 、 苯 为溶剂， 反应 24.0h， 生成 parviflorin
  参考文献：
  名称：

  有效的抗肿瘤番荔枝苷元 (+)-Parviflorin 的高效合成

  摘要：

  番荔枝苷是一类迅速增长的天然产物，受到了相当多的关注。1 许多成员具有多种生物效应，包括有效的细胞毒性、抗肿瘤和杀虫活性。 2,3 Parviflorin (1)，一种相对罕见的 C35 相邻双-THF acetogenin，由 McLaughlin 等人分离。来自 Asimina parViflora Duanl.4a 和来自 Annona bullata Rich.4b 的 Parviflorin 在对某些人实体瘤细胞系的细胞毒性方面表现出显着的选择性。5 光谱分析阐明了 1 的相对构型，4a 并使用 Mosher 确定了绝对构型方法论。6 化合物 1 显示的光谱数据与阿西霉素 (2) 的光谱数据非常相似。它们在 THF 核心处共享一个 threo/trans/threo/trans/threo 构型，并在 C(4) 位置共享一个羟基。虽然已经报道了 5 种双-THF 乙酰生成素或其立体异构体的合成，7

  DOI：

  10.1021/ja953781q
• 作为产物：
  描述：

  tert-butyl-[(3R,4R)-4-[tert-butyl(dimethyl)silyl]oxyhexa-1,5-diyn-3-yl]oxy-dimethylsilane 在 platinum(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 potassium osmate(VI) 、 copper(l) iodide 、 (DHQ)2-PHAL 盐酸 、 4-二甲氨基吡啶 、 甲基磺酰胺 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 二乙胺 、 叔丁醇 为溶剂， 反应 2.0h， 生成 (-)-(2R,3R,6R,7R,10R,11R)-1,2:3,6:7,10:11,12-tetraepoxydodecane
  参考文献：
  名称：

  全合成Longimicin C的迭代乙炔-环氧偶联策略

  摘要：

  首次合成了Longimicin C，它是一种天然的非乙酰丙酮原蛋白，具有C 2对称的双THF部分，并且在其含THF的区域和末端γ-内酯之间具有短的烃链。通过迭代的乙炔-环氧偶联策略成功完成了总合成。d-甘露糖醇用于建立含双THF的链段，其中的附加立体化学是通过Sharpless二羟基化和分子内Williamson醚化引入的。适当的末端乙炔的区域选择性环氧化物开口允许偶联和修饰所有四个片段，包括将三个必需的羟基引入目标骨架的适当位点。

  DOI：

  10.1016/j.tetlet.2005.05.145

文献信息

• In vitro Antitumor Activities of New Synthetic Bistetrahydrofuran Derivatives as Analogs of Annonaceous Acetogenins.
  作者：Shigeki SASAKI、Katsunori MARUTA、Hiroyuki NAITO、Rie MAEMURA、Eiji KAWAHARA、Minoru MAEDA

  DOI：10.1248/cpb.46.154

  日期：——

  We investigated the in vitro antitumor activities toward mouse and human cell lines of optically active synthetic bistetrahydrofuran (bis-THF) derivatives as analogs of Annonaceous acetogenins, which contain bis-THF, long unbranched alkyl chains, hydroxyl groups, and an α, β-unsaturated γ-lactone. These bis-THF derivatives were synthesized in a stereocontrolled manner, and have several modified structures at the alkyl side chains. We found that : 1) the unsaturated γ-lactone contributes to high potency in combination with the other less-functionalized alkyl chain, 2) the same absolute configuration of the bis-THF skeleton as that of the natural products produces more potent activity than the counterpart, 3) the alkyl chains and hydroxyl groups are crucial for exhibiting antitumor activity, 4) hydroxyl groups adjacent to the bis-THF skeleton may be replaced by amino or acylamino groups.

  我们研究了光学活性合成双四氢呋喃（bis-THF）衍生物对小鼠和人类细胞系的体外抗肿瘤活性，这些衍生物是茴香属植物炔苷的类似物，含有双-THF、长的未支化烷基链、羟基以及α、β-不饱和γ-内酯。这些双-THF 衍生物是以立体可控的方式合成的，烷基侧链的结构有多种变化。我们发现：1）不饱和γ-内酯与其他官能度较低的烷基链结合可产生较高的效力；2）双-THF 骨架的绝对构型与天然产物相同时，其活性比天然产物更强；3）烷基链和羟基对发挥抗肿瘤活性至关重要；4）双-THF 骨架邻近的羟基可被氨基或酰氨基取代。
• Novel acyclic ligands for metal cations based on the adjacent bistetrahydrofuran as analogs of natural Annonaceous acetogenins
  作者：Shigeki Sasaki、Katsunori Maruta、Hiroyuki Naito、Rie Maemura、Eiji Kawahara、Minoru Maeda

  DOI：10.1016/s0040-4020(97)10439-2

  日期：1998.3

  The acyclic ligands with an adjacent bistetrahydrofuran (THF) skeleton have been synthesized as analogs of bullatacin, a representative natural product in a family of Annonaceous acetogenins, and their binding properties toward metal cations have been investigated. The dihydroxyl bis-THF ligands with alkyl chains showed specific binding toward Ca2+, and those with acetamido groups exhibited potent binding with Ca2+ and Mg2+. The ligand with ether chains showed higher affinity toward Mg2+. These binding properties which depend on the nature of side chains and their stereochemistry have been analyzed by molecular modeling. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Synthesis and characterization of Δlac-acetogenins that potently inhibit mitochondrial complex I
  作者：Jean-Charles Chapuis、Omar Khdour、Xiaoqing Cai、Jun Lu、Sidney M. Hecht

  DOI：10.1016/j.bmc.2008.10.071

  日期：2009.3

  Four Dlac-acetogenins have been prepared and characterized as inhibitors of the mitochondrial respiratory chain, to define the effects of unsaturation within the alkyl substituents. In keeping with earlier reports, the presence of acetylenic functionalities within the alkyl substituents slightly diminished their potency of inhibition of NADH oxidase activity, which measures the overall transfer of electrons from NADH to oxygen through mitochondrial complexes I, III, and IV. In contrast, both of the acetylenic Dlac-acetogenins were far more active in a NADH-ubiquinone Q(1) oxidoreductase assay that measures complex I function per se. (C) 2008 Elsevier Ltd. All rights reserved.
• Essential structural factors of acetogenins, potent inhibitors of mitochondrial complex I
  作者：Tomoko Motoyama、Hiromi Yabunaka、Hideto Miyoshi

  DOI：10.1016/s0960-894x(02)00374-8

  日期：2002.8

  To elucidate the role of the hydrophobic alkyl tail of acetogenins in the inhibitory action, we synthesized an acetogenin derivative possessing the shortest tail (i.e., methyl group) and examined its inhibitory activity against bovine heart mitochondrial complex I. Our results indicated that the alkyl tail, which is one of the common structural features of natural acetogenins, is not an essential structural factor required for the potent inhibition. (C) 2002 Elsevier Science Ltd. All rights reserved.
• An iterative acetylene–epoxide coupling strategy for the total synthesis of longimicin C
  作者：Yan-Tao He、Song Xue、Tai-Shan Hu、Zhu-Jun Yao

  DOI：10.1016/j.tetlet.2005.05.145

  日期：2005.8

  Longimicin C, a naturally occurring annonaceous acetogenin possessing a C2-symmetrical bis-THF moiety and a short hydrocarbon chain between its THF-containing region and a terminal γ-lactone, was synthesized for the first time. The total synthesis was successfully achieved by an iterative acetylene–epoxide coupling strategy. d-Mannitol was used to establish the bis-THF-containing segment, in which

  首次合成了Longimicin C，它是一种天然的非乙酰丙酮原蛋白，具有C 2对称的双THF部分，并且在其含THF的区域和末端γ-内酯之间具有短的烃链。通过迭代的乙炔-环氧偶联策略成功完成了总合成。d-甘露糖醇用于建立含双THF的链段，其中的附加立体化学是通过Sharpless二羟基化和分子内Williamson醚化引入的。适当的末端乙炔的区域选择性环氧化物开口允许偶联和修饰所有四个片段，包括将三个必需的羟基引入目标骨架的适当位点。