(1R,4R,5R,8R)-4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol | 208646-61-1

• 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: (1R,4R,5R,8R)-4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol
• 英文别名: (1R,4R,5R,8R)-4-(benzenesulfonylmethyl)-4,8-dimethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol
• CAS: 208646-61-1
• 化学式: C₁₆H₂₂O₅S
• 分子量: 326.414
• InChiKey: PFAJNVCFGCXGRB-MIGQKNRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,4R,5R,8R)-4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol 在 吡啶 、 氯化亚砜 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 (1R,4R,5R,7R,8R)-4,8-dimethyl-7,8-epoxy-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]nonane
  参考文献：
  名称：

  A Short Synthesis and Biological Evaluation of Potent and Nontoxic Antimalarial Bridged Bicyclic β-Sulfonyl-Endoperoxides

  摘要：

  The syntheses and in vitro antimalarial. screening of 50 bridged, bicyclic endoperoxides of types 9-13 are reported. In contrast to antimalarial trioxanes of the artemisinin family, but like yingzhaosu A and arteflene, the peroxide function of compounds 9-13 is contained in a 2,3dioxabicyclo[3.3.1]nonane system 6. Peroxides 9 and 10 (RI = OH) are readily available through a multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a TOCO reaction). beta-Sulfenyl peroxides 9 and 10 (R-1 = OH) are converted into beta-sulfinyl and beta-sulfonyl peroxides of types 11-13 by controlled S-oxidation and manipulation of the tert-hydroxyl. group through acylation, alkylation, or dehydration followed by selective hydrogenation. Ten enantiopure beta-sulfbnyl peroxides of types 12 and 13 exhibit in vitro antimalarial activity comparable to that of artemisinin (IC50 = 6-24 nM against Plasmodium falciparum NF54). In vivo testing of a few selected peroxides against Plasmodium berghei N indicates that the antimalarial efficacies of beta-sulfonyl peroxides 39a, 46a, 46b, and 50a are comparable to those of some of the best antimalarial drugs and are higher than artemisinin against chloroquine-resistant Plasmodium yoelii ssp. NS. In view of the nontoxicity of beta-sulfonyl peroxides 39a, 46a, and 46b in mice, at high dosing, these compounds are regarded as promising antimalarial drug candidates.

  DOI：

  10.1021/jm020584a
• 作为产物：
  描述：

  (1R,4S,5R,8R)-4,8-dimethyl-4-phenylsulfenylmethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol 、 (1R,4R,5R,8R)-4,8-dimethyl-4-phenylsulfenylmethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol 在 间氯过氧苯甲酸 作用下， 生成 (1R,4R,5R,8R)-4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]nonan-8-ol
  参考文献：
  名称：

  2,3-dioxabicyclo[3.3.1]nonane derivatives and antimalarial

  摘要：

  2,3-二氧杂双环[3.3.1]壬烷衍生物，带有在位置4处的硫含功能基团，所选自磺酰基、亚磺酰基和亚硫酰基，通过甲基基团粘附在C(4)上，由结构式(A)表示，其中：X为氢、羟基、烷氧基，可选地被烷氧基或酰氧基取代，芳基烷氧基，可选地被烷氧基或芳氧基取代，M为氢、羟基、烷氧基、烯烷氧基、酰氧基，可选地被酰基或酰氧基取代，芳基烷氧基，芳基烯烷氧基，被烷氧基取代的草酸酯氧基，双(烷基)氨基或烷基(芳基)氨基，双(芳基烷基)氨基或被芳氧基取代的羰氧基，双(烷基)氨基，双(芳基烷基)氨基和烷基(芳基)氨基；或X和M一起表示碳-碳键或氧原子；L为氢或L和M一起表示碳-碳键；而Z要么是一个基团R--S(=O).sub.n --而Y为氢，要么Y是R--S(=O).sub.n --而Z为氢，其中R是烷基，可选地被烷氧基或烷氧羰基、环烷基、芳基或芳烷基取代，可选地被烷基、卤素或CF.sub.3取代；n为0、1或2，对于预防和/或治疗疟疾是有用的。

  公开号：

  US06166065A1

文献信息

• An efficient synthesis of bridged-bicyclic peroxides structurally related to antimalarial yingzhaosu A based on radical co-oxygenation of thiols and monoterpenes
  作者：Edward E Korshin、Roland Hoos、Alex M Szpilman、Leonid Konstantinovski、Gary H Posner、Mario D Bachi

  DOI：10.1016/s0040-4020(02)00126-6

  日期：2002.3

  Synthesis of β-sulfenyl endoperoxides 9 was achieved by a four component sequential free radical reaction based on the application of the thiol-olefin-co-oxygenation reaction to monoterpenes, followed by in situ treatment with triphenylphosphine. β-Sulfenyl endoperoxides 9 were oxidized with m-CPBA to β-sulfonyl endoperoxides 10. This process provides an efficient method for the preparation of peroxides

  β-亚砜基内过氧化物9的合成是基于四组分顺序自由基反应，该反应基于将硫醇-烯烃-共加氧反应应用于单萜，然后用三苯基膦进行原位处理。β-硫基内过氧化物9与被氧化米-CPBA到β-磺酰内过氧化物10。该方法提供了一种有效的方法，用于制备含有2号3-二氧杂双环[3.3.1]壬烷体系（2）的过氧化物，该体系具有应召素A（3）系列抗疟剂的特征。描述了一种用于鉴定立体异构体的简单NMR诊断工具。
• Synthesis and in vitro antimalarial activity of sulfone endoperoxides
  作者：Mario D. Bachi、Edward E. Korshin、Poonsakdi Ploypradith、Jared N. Cumming、Suji Xie、Theresa A. Shapiro、Gary H. Posner

  DOI：10.1016/s0960-894x(98)00141-3

  日期：1998.4

  acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).

  通过短而有效的方法，由R制备了一系列在8位（4）带有多个取代基的4,8-二甲基-4-苯基磺酰基甲基-2,3-二氧杂双环[3.3.1] + ++壬烷-（+）-柠檬烯。关键反应包括硫醇氧共氧化，以及与内过氧官能团相容的位阻叔醇的烷基化和酰化。已发现在结构上与yingzhaosu A（2）有关的某些化合物4具有与青蒿素（1）相当的体外抗疟活性，并优于arteflene（3）。
• 2,3-DIOXABICYCLO 3.3.1]NONANE DERIVATIVES AND ANTIMALARIAL PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
  申请人：YEDA RESEARCH AND DEVELOPMENT COMPANY, LTD.

  公开号：EP1021403B1

  公开（公告）日：2005-04-20
• US6166065A
  申请人：——

  公开号：US6166065A

  公开（公告）日：2000-12-26