(3S,6R)-3,6-Dicyclopentyl-3,6-dihydro-[1,2]dioxine | 682344-38-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三氧烷
• 英文名称: (3S,6R)-3,6-Dicyclopentyl-3,6-dihydro-[1,2]dioxine
• 英文别名: (3S,6R)-3,6-dicyclopentyl-3,6-dihydro-1,2-dioxine
• CAS: 682344-38-3
• 化学式: C₁₄H₂₂O₂
• 分子量: 222.327
• InChiKey: GNOIBLWMYCDPJA-OKILXGFUSA-N

物化性质

• 沸点：
  288.0±20.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 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：

  (3S,6R)-3,6-Dicyclopentyl-3,6-dihydro-[1,2]dioxine 在 salcomine potassium osmate(VI) 、 N-甲基吲哚酮 、 对甲苯磺酸 、 柠檬酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 41.0h， 生成 (+/-)-(3aS,6S,6aS)-2,2-dicyclopentyl-2,2-dimethylperhydrofuro[3,4-d][1,3]dioxol-4-ol
  参考文献：
  名称：

  Osmium Catalyzed Dihydroxylation of 1,2-Dioxines:  A New Entry for Stereoselective Sugar Synthesis

  摘要：

  A series of 3,6-substituted 3,6-dihydro-1,2-dioxines were dihydroxylated with osmium tetroxide to furnish 1,2-dioxane-4,5-diols (peroxy diols) in yields ranging from 33% to 98% and with de values not less than 90%. The peroxy diols were then reduced to generate a stereospecific tetraol core with R, R, S, S or "allitol" stereochemistry. The peroxy diols and their acetonide derivatives were also ring-opened with Co(II) salen complexes to give novel hydroxy ketones in 77-100% yield, including the natural sugar psicose. Importantly, preliminary work on the catalytic asymmetric ring-opening of meso-peroxy diols using the Co(II) Jacobsens's catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines is possible.

  DOI：

  10.1021/jo060949p
• 作为产物：
  描述：

  [(Z)-4-cyclopentylbut-2-enyl]cyclopentane 在 氧气 、 Rose Bengal bis(triethylammonium) salt 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 (3S,6R)-3,6-Dicyclopentyl-3,6-dihydro-[1,2]dioxine
  参考文献：
  名称：

  Novel endoperoxides: Synthesis and activity against Candida species

  摘要：

  Fifteen new endoperoxides have been synthesised and tested for activity against pathogenic Candida species. These endoperoxides can be prepared in high yields, in one to three steps, from inexpensive starting materials. Despite chemical and structural similarities, their inhibitory activity against Candida growth varied greatly from one endoperoxide to another, and one species to another. This study of susceptibility to endoperoxide compounds presented here may lead to the development of potent new antifungal agents. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2005.10.101

文献信息

• Novel Endoperoxide Antimalarials:  Synthesis, Heme Binding, and Antimalarial Activity
  作者：Dennis K. Taylor、Thomas D. Avery、Ben W. Greatrex、Edward R. T. Tiekink、Ian G. Macreadie、Peter I. Macreadie、Adam D. Humphries、Martha Kalkanidis、Emma N. Fox、Nectarios Klonis、Leann Tilley

  DOI：10.1021/jm0305319

  日期：2004.3.1

  We report the synthesis of a series of novel epoxy endoperoxide compounds that can be prepared in high yields in one to three steps from simple starting materials. Some of these compounds inhibit the growth of Plasmodium falciparum in vitro. Structure-activity studies indicate that an endoperoxide ring bisubstituted with saturated cyclic moieties is the pharmacophore. To study the molecular basis of

  我们报告了一系列新型环氧内过氧化物化合物的合成，这些化合物可以从简单的起始原料通过一到三个步骤以高收率制备。这些化合物中的一些在体外抑制恶性疟原虫的生长。结构活性研究表明，被饱和环状部分双取代的内过氧化物环是药效团。为了研究这些新型抗疟疾化合物作用的分子基础，我们研究了它们与氧化和还原形式的血红素相互作用的能力。一些化合物以类似于氯喹和其他4-氨基喹啉的方式与氧化血红素相互作用，而一些化合物则与还原的血红素相互作用。但是，抗疟疾效力水平与这些活动并没有很好的相关性，
• Artemisinin and a Series of Novel Endoperoxide Antimalarials Exert Early Effects on Digestive Vacuole Morphology
  作者：Maria del Pilar Crespo、Thomas D. Avery、Eric Hanssen、Emma Fox、Tony V. Robinson、Peter Valente、Dennis K. Taylor、Leann Tilley

  DOI：10.1128/aac.00609-07

  日期：2008.1

  Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of Plasmodium falciparum . A trans -epoxide with respect to the peroxide linkage increases the activity compared to that of its cis -epoxy counterpart or the parent endoperoxide. The novel endoperoxides do not show a strong interaction with artemisinin. We have compared the mechanism of action of the novel endoperoxides with that of artemisinin. Electron microscopy reveals that the novel endoperoxides cause the early accumulation of endocytic vesicles, while artemisinin causes the disruption of the digestive vacuole membrane. At longer incubation times artemisinin causes extensive loss of organellar structures, while the novel endoperoxides cause myelin body formation as well as the accumulation of endocytic vesicles. An early event following endoperoxide treatment is the redistribution of the pH-sensitive probe LysoSensor Blue from the digestive vacuole to punctate structures. By contrast, neither artemisinin nor the novel endoperoxides caused alterations in the morphology of the endoplasmic reticulum nor showed antagonistic antimalarial activity when they were used with thapsigargin. Analysis of rhodamine 123 uptake by P. falciparum suggests that disruption of the mitochondrial membrane potential occurs as a downstream effect rather than as an initiator of parasite killing. The data suggest that the digestive vacuole is an important initial site of endoperoxide antimalarial activity.

  摘要 目前，蒿甲素及其衍生物已成为抗疟治疗的主要药物；然而，人们对它们的作用机制却知之甚少。我们报告了一系列新型环氧内过氧化物的合成过程，这些化合物可以用简单的起始原料高产率地制备。用烷基或苄基侧链二取代的内过氧化物对恶性疟原虫的氯喹敏感菌株和耐药菌株的生长都有有效的抑制作用。 恶性疟原虫 .A 反式 -过氧化物连接的反式环氧化物比其顺式环氧化物的活性更强。 顺式 -环氧化物或母体内过氧化物的活性。新型内过氧化物不会与青蒿素产生强烈的相互作用。我们比较了新型内过氧化物与青蒿素的作用机制。电子显微镜显示，新型内过氧化物会导致内囊泡的早期积聚，而青蒿素则会导致消化泡膜的破坏。在较长的培养时间内，青蒿素会导致细胞器结构的广泛丧失，而新型内过氧化物则会导致髓鞘体的形成以及内囊泡的积累。内过氧化物处理后的一个早期现象是 pH 敏感探针 LysoSensor Blue 从消化泡重新分布到点状结构。相比之下，青蒿素和新型内过氧化物既不会引起内质网形态的改变，也不会在与硫糖苷一起使用时显示出拮抗抗疟活性。分析恶性疟原虫对罗丹明 123 的吸收 恶性疟原虫 分析表明，线粒体膜电位的破坏是一种下游效应，而不是杀死寄生虫的始作俑者。数据表明，消化泡是内过氧化物抗疟活性的重要初始场所。