4α-hydroxymenthol | 18374-79-3

• 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: 4α-hydroxymenthol
• 英文别名: (-)-(1S,3R,4S,6S)-6-hydroxymenthol；(1S,2S,4R,5S)-2-methyl-5-propan-2-ylcyclohexane-1,4-diol
• CAS: 18374-79-3
• 化学式: C₁₀H₂₀O₂
• 分子量: 172.268
• InChiKey: TXISQGBRDPUIBI-AATLWQCWSA-N

物化性质

• 熔点：
  143 °C
• 沸点：
  275.9±8.0 °C(Predicted)
• 密度：
  0.998±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4α-hydroxymenthol 、 乙酰氯 在 吡啶 作用下， 以 氯仿 为溶剂， 反应 1.0h， 生成 (-)-(1S,3R,4S,6S)-6-hydroxymenthyl diacetate
  参考文献：
  名称：

  Lytic Activity of l-Menthol Derivatives against the Snow Blight Disease Fungus, Micronectriella nivalis

  摘要：

  Lytic activity of l-menthol (1) derivatives [(-)-(1S,3R,4S,6S)-6-hydroxymenthol (2), (-)-(1S,3R,4S)-1-hydroxymenthol (3), and (+)-(1S,3R,4R,6S)-6,8-dihydroxymenthol (4)] against the snow blight disease fungus, Micronectriella nivalis was investigated. Compounds 2, 3, and 4 had 85.0, 63.9, and 81.9% lytic activity, respectively, at a concentration of 0.2 mg/mL. The activity of each of the three compounds increased in a dose-response manner. To study the structure-activity relationship, acetyl esters of 1-4 [(-)-menthyl acetate (1Ac), (-)-6-hydroxymenthyl diacetate (2Ac), (-)-1-hydroxymenthyl 3-monoacetate (3Ac), and (-)-6,8-dihydroxymenthyl 3,6-diacetate (4Ac)] were synthesized with yields of 80.2-99.8% and were also assayed. The acetyl esters of 1Ac, 2Ac, 3Ac, and 4Ac had 51.2, 91.5, 66.0, and 95.2% lytic activity, respectively, at a concentration of 0.2 mg/mL, and these compounds showed further high lytic activity compared with the alcohols of 1-4. These acetyl esters also showed higher lytic activity as their concentration was increased. Of particular interest is the fact that 2Ac and 4Ac both had higher lytic activity at 0.05-0.2 mg/mL compared with copper 8-hydroxyquinolate, a standard chemical widely used to control snow blight. This is the first report on lytic activity of I-menthol derivatives.

  DOI：

  10.1021/jf0210831
• 作为产物：
  描述：

  在 lithium aluminium tetrahydride 作用下， 生成 4α-hydroxymenthol
  参考文献：
  名称：

  Enzymatic hydroxylation of an unactivated methylene C–H bond guided by molecular dynamics simulations

  摘要：

  次级代谢途径中的酶的特点是将强大的反应性与精湛的位点选择性相结合。然而，由于底物范围和可扩展性的限制，这些生物催化工具在有机合成中的应用仍未得到充分利用。在这里，我们报告了如何通过计算引导的蛋白质和底物工程改造匹红霉素途径中的单加氧酶（PikC）的反应性，并将其应用于未活化亚甲基 CâH 键的氧化。分子动力学和量子力学计算被用来开发 PikC 介导的 CâH 氧化作用的底物范围、位点选择性和立体选择性的预测模型。通过计算筛选出了一套薄荷醇衍生物，并通过体外反应进行了评估，其中每种底物都符合选择性和转化为产物的预测模型。这一平台还从基于薄荷醇的底物扩展到各种底物核心的选择性羟基化，从环状化合物到融合双环化合物和桥接双环化合物。通过蛋白质和底物工程改造了单加氧酶（P450 PikC）的反应性，并将其应用于氧化未活化的亚甲基 CâH 键。蛋白质工程以分子动力学和量子力学计算为指导，建立了 CâH 羟基化的底物范围、位点选择性和立体选择性的预测模型。

  DOI：

  10.1038/nchem.2285

文献信息

• Fungal Transformation of (1<i>R</i>,2<i>S</i>,5<i>R</i>)-(−)-Menthol by <i>Cephalosporium </i><i>a</i><i>phidicola</i>
  作者：Atta-ur-Rahman、Muhammad Yaqoob、Afgan Farooq、Shazia Anjum、Fahim Asif、M. Iqbal Choudhary

  DOI：10.1021/np980057n

  日期：1998.11.1

  Incubation of (1R,2S,5R)-(-)-menthol (1) with Cephalosporium aphidicola for 12 days yielded the six oxidized metabolites: 10-acetoxymenthol (2), 7-hydroxymenthol (3), 4alpha-hydroxymenthol (4), 3alpha-hydroxymenthol (5), 9-hydroxymenthol (6), and 10-hydroxymenthol (7). The structures of the novel compounds 2, 4, 5, and 7 were assigned by interpretation of their spectral data.
• Lytic Activity of <i>l</i>-Menthol Derivatives against the Snow Blight Disease Fungus, <i>Micronectriella nivalis</i>
  作者：Mitsuo Miyazawa、Hideki Kawazoe、Yuji Sumi、Mitsuro Hyakumachi

  DOI：10.1021/jf0210831

  日期：2003.3.1

  Lytic activity of l-menthol (1) derivatives [(-)-(1S,3R,4S,6S)-6-hydroxymenthol (2), (-)-(1S,3R,4S)-1-hydroxymenthol (3), and (+)-(1S,3R,4R,6S)-6,8-dihydroxymenthol (4)] against the snow blight disease fungus, Micronectriella nivalis was investigated. Compounds 2, 3, and 4 had 85.0, 63.9, and 81.9% lytic activity, respectively, at a concentration of 0.2 mg/mL. The activity of each of the three compounds increased in a dose-response manner. To study the structure-activity relationship, acetyl esters of 1-4 [(-)-menthyl acetate (1Ac), (-)-6-hydroxymenthyl diacetate (2Ac), (-)-1-hydroxymenthyl 3-monoacetate (3Ac), and (-)-6,8-dihydroxymenthyl 3,6-diacetate (4Ac)] were synthesized with yields of 80.2-99.8% and were also assayed. The acetyl esters of 1Ac, 2Ac, 3Ac, and 4Ac had 51.2, 91.5, 66.0, and 95.2% lytic activity, respectively, at a concentration of 0.2 mg/mL, and these compounds showed further high lytic activity compared with the alcohols of 1-4. These acetyl esters also showed higher lytic activity as their concentration was increased. Of particular interest is the fact that 2Ac and 4Ac both had higher lytic activity at 0.05-0.2 mg/mL compared with copper 8-hydroxyquinolate, a standard chemical widely used to control snow blight. This is the first report on lytic activity of I-menthol derivatives.
• Enzymatic hydroxylation of an unactivated methylene C–H bond guided by molecular dynamics simulations
  作者：Alison R. H. Narayan、Gonzalo Jiménez-Osés、Peng Liu、Solymar Negretti、Wanxiang Zhao、Michael M. Gilbert、Raghunath O. Ramabhadran、Yun-Fang Yang、Lawrence R. Furan、Zhe Li、Larissa M. Podust、John Montgomery、K. N. Houk、David H. Sherman

  DOI：10.1038/nchem.2285

  日期：2015.8

  The hallmark of enzymes from secondary metabolic pathways is the pairing of powerful reactivity with exquisite site selectivity. The application of these biocatalytic tools in organic synthesis, however, remains under-utilized due to limitations in substrate scope and scalability. Here, we report how the reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified through computationally guided protein and substrate engineering, and applied to the oxidation of unactivated methylene C–H bonds. Molecular dynamics and quantum mechanical calculations were used to develop a predictive model for substrate scope, site selectivity and stereoselectivity of PikC-mediated C–H oxidation. A suite of menthol derivatives was screened computationally and evaluated through in vitro reactions, where each substrate adhered to the predicted models for selectivity and conversion to product. This platform was also expanded beyond menthol-based substrates to the selective hydroxylation of a variety of substrate cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds. The reactivity of a monooxygenase (P450 PikC) has been modified through protein and substrate engineering, and applied to the oxidation of unactivated methylene C–H bonds. The protein engineering was guided by using molecular dynamics and quantum mechanical calculations to develop a predictive model for substrate scope, site selectivity and stereoselectivity of the C–H hydroxylation.

  次级代谢途径中的酶的特点是将强大的反应性与精湛的位点选择性相结合。然而，由于底物范围和可扩展性的限制，这些生物催化工具在有机合成中的应用仍未得到充分利用。在这里，我们报告了如何通过计算引导的蛋白质和底物工程改造匹红霉素途径中的单加氧酶（PikC）的反应性，并将其应用于未活化亚甲基 CâH 键的氧化。分子动力学和量子力学计算被用来开发 PikC 介导的 CâH 氧化作用的底物范围、位点选择性和立体选择性的预测模型。通过计算筛选出了一套薄荷醇衍生物，并通过体外反应进行了评估，其中每种底物都符合选择性和转化为产物的预测模型。这一平台还从基于薄荷醇的底物扩展到各种底物核心的选择性羟基化，从环状化合物到融合双环化合物和桥接双环化合物。通过蛋白质和底物工程改造了单加氧酶（P450 PikC）的反应性，并将其应用于氧化未活化的亚甲基 CâH 键。蛋白质工程以分子动力学和量子力学计算为指导，建立了 CâH 羟基化的底物范围、位点选择性和立体选择性的预测模型。