(1S,2Z,4R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4-ol-6-one | 1361537-19-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,2Z,4R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4-ol-6-one
• 英文别名: (2E,6E,10S,11Z,13R)-13-methoxy-3,7,13-trimethyl-10-propan-2-ylcyclotetradeca-2,6,11-trien-1-one
• CAS: 1361537-19-0
• 化学式: C₂₁H₃₄O₂
• 分子量: 318.5
• InChiKey: XEUGRJJXIPPPSC-UJMONDQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4,6-diol 在 吡啶 、 铬酸 作用下， 生成 (1S,2Z,4R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4-ol-6-one 、 (1S,2E,4R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4-ol-6-one
  参考文献：
  名称：

  Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: Preliminary structure–activity relationship and pharmacophore modeling

  摘要：

  Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice. Cembranoid 1 acts by noncompetitive inhibition of the alpha 7 nicotinic acetylcholine receptor. This study aims at establishing a preliminary structure-activity relationship to define the neuroprotective cembranoid pharmacophores using the hippocampal slice assay and pharmacophore modeling. Fourteen natural, semisynthetic, or biocatalytic cembranoid analogues 2-15 related to 1 were tested for their capacity to protect the population spikes from DFP-induced damage and intrinsic toxicity. Twelve cembranoids caused significant reversal of DFP toxicity; only 3 active analogues displayed minor intrinsic toxicity at 10 mu M. The C-4 epimer of 1 (2) and the 4-O-methyl ether analogue of 1 (3), were totally devoid of neuroprotective activity. The results suggested a model for cembranoid binding where the hydrophobic ring surface binds to a hydrophobic (Hbic) patch on the receptor molecule and an electronegative atom (oxygen or sulfur) in proper spatial relationship to the ring surface interacts with an electropositive group in the receptor binding site. A pharmacophore model consisting of 1 hydrogen bond acceptor (HBA), 2 Hbic, and 10 exclusion spheres was established using HipHop-REFINE and supported the above mentioned pharmacophoric hypothesis. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.018

文献信息

• Bioactive Natural, Biocatalytic, and Semisynthetic Tobacco Cembranoids
  作者：Hany Baraka、Mohammad Khanfar、John Williams、Emad El-Giar、Khalid El Sayed

  DOI：10.1055/s-0030-1250478

  日期：2011.3

  The two major Nicotiana tabacum tobacco cembranoids, (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and its C-4 epimer, exhibit a wide range of interesting biological activities. Although the tumorigenesis inhibition activity of tobacco cembranoids have been known since the mid 1980′s, only a limited number of investigations have targeted their optimization and structure-activity relationship. This study reports the isolation of the new (1S,2E,4S,6E,8S,11E)-2,6,11-cembratriene-8-O-methyl-4,8-diol (3) and the known (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4,6-diol (2) from fresh N. tabacum leaves. Cembranoid 2 showed good anti-migratory activity against prostate cancer cell lines, and was therefore subjected to microbial transformation and semisynthetic optimization studies. Biotransformation of 2 using the fungal strains Cunninghamella NRRL 5695 and Mucor ramannianus ATCC 9628 afforded new (4 and 5) and known (6 and 7) metabolites. Semisynthetic esterification, oxidation, epoxidation, and reaction with Lawesson's reagent afforded the new products 8–14. Cembranoid 2 and its epoxidation product 9 showed potent anti-migratory activities against the highly metastatic human prostate cancer cell lines PC-3M-CT+ (spheroid disaggregation assay) and PC-3 (wound-healing assay).

  烟草烟碱（Nicotiana tabacum）的两种主要的烟草烟碱（cembratranoids），即（1S,2E,4R,6R,7E,11E）-2,7,11-cembratriene-4,6-diol（1）及其 C-4 epimer，具有多种有趣的生物活性。尽管早在 20 世纪 80 年代中期，人们就已经知道烟草 cembranoids 具有抑制肿瘤发生的活性，但针对其优化和结构-活性关系的研究为数不多。本研究报告了从烟草鲜叶中分离出的新的(1S,2E,4S,6E,8S,11E)-2,6,11-cembratriene-8-O-methyl-4,8-diol (3)和已知的(1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4,6-diol (2)。2 对前列腺癌细胞株具有良好的抗迁移活性，因此对其进行了微生物转化和半合成优化研究。利用真菌菌株 Cunninghamella NRRL 5695 和 Mucor ramannianus ATCC 9628 对 2 进行生物转化，得到了新的代谢物（4 和 5）和已知的代谢物（6 和 7）。通过半合成酯化、氧化、环氧化以及与 Lawesson 试剂反应，得到了新产品 8-14。Cembranoid 2 及其环氧化产物 9 对高度转移的人类前列腺癌细胞系 PC-3M-CT+（球形体分解试验）和 PC-3（伤口愈合试验）显示出强大的抗迁移活性。
• NEURONAL CIRCUIT-DEPENDENT NEUROPROTECTION BY INTERACTION BETWEEN NICOTINIC RECEPTORS
  申请人：Ferchmin Peter Andrew

  公开号：US20130165495A1

  公开（公告）日：2013-06-27

  A method of inhibiting excitotoxicity by indirectly activating α4β2 nicotinic acetylcholine receptors (nAChRs) which indirectly activate synaptic AMPA and NMDA receptors is disclosed Inhibitors of α7 nACHRs, such as macrocyclic diterpenoids, more specifically cembranoids or methyllycaconitine (MLA), indirectly activate α4β2 nAChRs and can be used to treat neurodegenerative diseases, including, but not limited to, Alzheimer's Disease, Parkinson Disease, AIDS related dementia and the delayed effects of stroke. They can also be used to treat diseases associated with neuronal impairment, including, but not limited to glaucoma caused by optical nerve damage, delayed effects of epilepsy; and multiple sclerosis.