(1S,2E,4R,6R,7E,11E,10S)-2,7,11-cembratriene-4,6,10-triol | 149403-70-3

• 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,2E,4R,6R,7E,11E,10S)-2,7,11-cembratriene-4,6,10-triol
• 英文别名: (10S)-β-cembrenetriol；(1R,3R,4E,7S,8E,12S,13E)-1,5,9-trimethyl-12-propan-2-ylcyclotetradeca-4,8,13-triene-1,3,7-triol
• CAS: 149403-70-3
• 化学式: C₂₀H₃₄O₃
• 分子量: 322.488
• InChiKey: ZRUCLTHCKNSADG-LOXHLNSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol 在 吡啶 、 铬酸 作用下， 生成 (1S,2E,4R,6R,7E,11E,10S)-2,7,11-cembratriene-4,6,10-triol
  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

• One-Pot, Two-Step Hydroxylation of the Macrocyclic Diterpenoid β-Cembrenediol Catalyzed by P450 BM3 Mutants
  作者：Priska Le-Huu、Dušan Petrović、Birgit Strodel、Vlada B. Urlacher

  DOI：10.1002/cctc.201600973

  日期：2016.12.19

  Cytochrome P450 monooxygenases (P450s) are involved in the biosynthesis of a wide range of bioactive secondary metabolites. They often introduce several oxy functionalities at different positions of a substrate through multiple steps and produce a range of oxidized derivatives. Herein, we describe a one‐pot two‐step hydroxylation of the diterpenoid β‐cembrenediol isolated from the plant Nicotiana tabacum

  细胞色素P450单加氧酶（P450s）参与多种生物活性次级代谢产物的生物合成。它们通常通过多个步骤在基材的不同位置引入多个氧基官能团，并产生一系列氧化衍生物。在这里，我们描述了从植物烟草中分离出的二萜类β-脑二醇的一锅两步羟基化。这个由14个成员组成的大环化合物具有神经保护作用，并且与它的氧化衍生物一起具有药用价值。区域选择性P450 BM3突变体F87A / I263L和V78A / F87G催化的顺序羟基化产生了差向异构体（9 S，10 R / S）-非对映体比例为48:52的β-脑四烯醇。在第二步骤中用L75A / V78A / F87G替换突变体V78A / F87G将非对映异构体比例提高至10:90。新引入的羟基的绝对构型是通过NMR光谱的量子力学计算确定的。