(2R,6S)-6-hexyl-2-(hydroxymethyl)tetrahydropyran | 1261359-79-8

• 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: (2R,6S)-6-hexyl-2-(hydroxymethyl)tetrahydropyran
• 英文别名: [(2R,6S)-6-hexyloxan-2-yl]methanol
• CAS: 1261359-79-8
• 化学式: C₁₂H₂₄O₂
• 分子量: 200.321
• InChiKey: VRSGBDVVCRWEEP-NWDGAFQWSA-N

物化性质

• 沸点：
  272.3±8.0 °C(Predicted)
• 密度：
  0.911±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2R,6S)-6-hexyl-2-(hydroxymethyl)tetrahydropyran 在 偶氮二甲酸二异丙酯 、 N,N-二异丙基乙胺 、 三苯基膦 、 叠氮磷酸二苯酯 作用下， 以 四氢呋喃 为溶剂， 反应 16.33h， 以37%的产率得到(2R,6S)-2-azidomethyl-6-hexyltetrahydropyran
  参考文献：
  名称：

  Non-natural Acetogenin Analogues as PotentTrypanosoma bruceiInhibitors

  摘要：

  AbstractNeglected tropical diseases remain a serious global health concern. Here, a series of novel bis‐tetrahydropyran 1,4‐triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4‐triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure–activity relationship studies. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti‐HAT agents.

  DOI：

  10.1002/cmdc.201402272
• 作为产物：
  描述：

  6-benzyloxy-1-hexene 在 magnesium 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 45.0h， 生成 (2R,6S)-6-hexyl-2-(hydroxymethyl)tetrahydropyran
  参考文献：
  名称：

  Non-natural Acetogenin Analogues as PotentTrypanosoma bruceiInhibitors

  摘要：

  AbstractNeglected tropical diseases remain a serious global health concern. Here, a series of novel bis‐tetrahydropyran 1,4‐triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4‐triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure–activity relationship studies. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti‐HAT agents.

  DOI：

  10.1002/cmdc.201402272

文献信息

• Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective<i>Trypanosoma brucei</i>Inhibitors
  作者：Gordon J. Florence、Andrew L. Fraser、Eoin R. Gould、Elizabeth F. King、Stefanie K. Menzies、Joanne C. Morris、Marie I. Thomson、Lindsay B. Tulloch、Marija K. Zacharova、Terry K. Smith

  DOI：10.1002/cmdc.201600210

  日期：2016.7.19

  an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world's poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds

  由寄生虫感染引起的被忽视的热带病是一个持续不断的问题。它们是人类和动物健康的负担，对世界上最贫穷的国家具有最大的破坏性影响。在我们先前报道的三唑类似物的基础上，在这项研究中，我们描述了其他新颖的杂环产乙酸素启发的衍生物，即3,5-异恶唑，呋喃喃和呋喃聚糖的合成和生物学测试。这些化合物中的几种保持了对布鲁氏锥虫的低微摩尔水平的抑制作用，而对哺乳动物细胞却没有可观察到的抑制作用，从而导致了新的用于选择性治疗的先导化合物的可能性。
• Synthesis and Stereochemical Assignment of (+)-Chamuvarinin
  作者：Gordon J. Florence、Joanne C. Morris、Ross G. Murray、Jonathan D. Osler、Vanga R. Reddy、Terry K. Smith

  DOI：10.1021/ol1028699

  日期：2011.2.4

  (+)-chamuvarinin, isolated from the root extract of Uvaria Chamae, utilizes a convergent modular strategy to construct the adjacently linked C15−C28 ether array, followed by a late-stage Julia−Kocienski olefination to append the butenolide motif. This constitutes the first total synthesis of (+)-chamuvarinin, defining the relative and absolute configuration of this unique annonaceous acetogenin.

  (+)-chamuvarinin 的立体控制全合成，从Uvaria Chamae 的根提取物中分离，利用收敛模块化策略构建相邻连接的 C15-C28 醚阵列，然后是后期 Julia-Kocienski 烯化以附加丁烯内酯主题。这构成了 (+)-chamuvarinin 的首次全合成，定义了这种独特的番荔枝素的相对和绝对构型。
• Total Synthesis, Stereochemical Assignment, and Biological Activity of Chamuvarinin and Structural Analogues
  作者：Gordon J. Florence、Joanne C. Morris、Ross G. Murray、Raghava R. Vanga、Jonathan D. Osler、Terry K. Smith

  DOI：10.1002/chem.201204527

  日期：2013.6.17

  butenolide. The inherent flexibility of our coupling strategy led to a streamlined synthesis with 17 steps in the longest sequence (2.2 % overall yield), in which the key bond couplings are reversed. In addition, a series of structural analogues of chamuvarinin have been prepared and screened for activity against HeLa cancer cell lines and both the bloodstream and insect forms of Trypanosoma brucei

  （+）-香豆素的高度立体控制的合成已在20个步骤中以1.5％的总产率完成。关键的片段偶联反应是将炔烃8添加到醛7中（在Felkin–Anh的控制下），然后进行两步活化/环化反应以封闭C20–C23 2,5–顺式取代的四氢呋喃环和在C8–C9处的Julia–Kocienski烯烃基引入末端丁烯内酯。我们偶联策略的固有灵活性导致了最长序列中17个步骤的精简合成（总产率为2.2％），其中键键偶联被颠倒了。此外，已经制备了一系列沙穆伐林的结构类似物，并筛选了针对HeLa癌细胞系以及布鲁氏锥虫（Trypanosoma brucei）的血流和昆虫形式的活性，布鲁氏锥虫是造成非洲昏睡病的寄生虫。
• Non-natural Acetogenin Analogues as Potent<i>Trypanosoma brucei</i>Inhibitors
  作者：Gordon J. Florence、Andrew L. Fraser、Eoin R. Gould、Elizabeth F. B. King、Stefanie K. Menzies、Joanne C. Morris、Lindsay B. Tulloch、Terry K. Smith

  DOI：10.1002/cmdc.201402272

  日期：2014.11

  AbstractNeglected tropical diseases remain a serious global health concern. Here, a series of novel bis‐tetrahydropyran 1,4‐triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4‐triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure–activity relationship studies. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti‐HAT agents.