(1-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)methanol | 25634-94-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (1-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)methanol
• 英文别名: 1-Hydroxymethyl-1-methyl-tetralin；(1-methyl-3,4-dihydro-2H-naphthalen-1-yl)methanol
• CAS: 25634-94-0
• 化学式: C₁₂H₁₆O
• 分子量: 176.258
• InChiKey: BVOXKRPQUJYDDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)methanol 在 chromium(VI) oxide 、 叔丁基过氧化氢 、 草酰氯 、 potassium carbonate 、 二甲基亚砜 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 4-ethynyl-4-methyl-3,4-dihydronaphthalen-1(2H)-one
  参考文献：
  名称：

  New Monocyclic, Bicyclic, and Tricyclic Ethynylcyanodienones as Activators of the Keap1/Nrf2/ARE Pathway and Inhibitors of Inducible Nitric Oxide Synthase

  摘要：

  A monocyclic compound 3 (3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile) is a highly reactive Michael acceptor leading to reversible adducts with nucleophiles, which displays equal or greater potency than the pentacyclic triterpenoid CDDO in inflammation and carcinogenesis related assays. Recently, reversible covalent drugs, which bind with protein targets but not permanently, have been gaining attention because of their unique features. To explore such reversible covalent drugs, we have synthesized monocyclic, bicyclic, and tricyclic compounds containing 3 as an electrophilic fragment and evaluated them as activators of the Keap1/Nrf2/ARE pathway and inhibitors of iNOS. Notably, these compounds maintain the unique features of the chemical reactivity and biological potency of 3. Among them, a monocyclic compound 5 is the most potent in these assays while a tricyclic compound 14 displays a more robust and specific activation profile compared to 5. In conclusion, we demonstrate that 3 is a useful electrophilic fragment for exploring reversible covalent drugs.

  DOI：

  10.1021/acs.jmedchem.5b00393
• 作为产物：
  描述：

  1,2,3,4,-四氢-1-萘甲酸甲酯 在 lithium aluminium tetrahydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 21.67h， 生成 (1-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)methanol
  参考文献：
  名称：

  New Monocyclic, Bicyclic, and Tricyclic Ethynylcyanodienones as Activators of the Keap1/Nrf2/ARE Pathway and Inhibitors of Inducible Nitric Oxide Synthase

  摘要：

  A monocyclic compound 3 (3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile) is a highly reactive Michael acceptor leading to reversible adducts with nucleophiles, which displays equal or greater potency than the pentacyclic triterpenoid CDDO in inflammation and carcinogenesis related assays. Recently, reversible covalent drugs, which bind with protein targets but not permanently, have been gaining attention because of their unique features. To explore such reversible covalent drugs, we have synthesized monocyclic, bicyclic, and tricyclic compounds containing 3 as an electrophilic fragment and evaluated them as activators of the Keap1/Nrf2/ARE pathway and inhibitors of iNOS. Notably, these compounds maintain the unique features of the chemical reactivity and biological potency of 3. Among them, a monocyclic compound 5 is the most potent in these assays while a tricyclic compound 14 displays a more robust and specific activation profile compared to 5. In conclusion, we demonstrate that 3 is a useful electrophilic fragment for exploring reversible covalent drugs.

  DOI：

  10.1021/acs.jmedchem.5b00393

文献信息

• Synthesis and biological activity of both enantiomers of kujigamberol isolated from 85-million-years-old Kuji amber
  作者：Yue Qi Ye、Hiroyuki Koshino、Daisuke Hashizume、Yuki Minamikawa、Ken-ichi Kimura、Shunya Takahashi

  DOI：10.1016/j.bmcl.2012.05.022

  日期：2012.7

  and (3) optical resolution of (±)-1 using chromatographical separation of the corresponding camphanates. X-ray crystallographical analysis of p-bromobenzoate obtained from the more polar camphanate that was identical with a natural derivative, revealed natural kujigamberol to have an S-configuration. Both the natural enantiomer and its (R)-antipode showed the same inhibitory activity toward the mutant

  通过全合成确定降冰片烷萜类化合物，苦瓜糖醇（1）的完整结构。总合成的关键特征是（1）通过苯甲酰胺的邻位化来安装异戊基；（2）通过RCM反应构建四氢萘酮；（3）使用色谱分离法测定（±）-1的光学拆分度。相应的樟脑。从极性更大的樟脑酸酯获得的对-溴苯甲酸酯的X射线晶体学分析与天然衍生物相同，表明天然的苦瓜酚具有S-构型。天然对映体及其（R）-对映体对突变酵母和HL - 60细胞具有相同的抑制活性，而在C-8和（±）-1的9位上没有烷基的简单类似物则没有这种活性。
• Access to Benzylic Quaternary Carbons from Aromatic Ketones
  作者：You Li、Jingpeng Han、Han Luo、Qiaoyu An、Xiao-Ping Cao、Baosheng Li

  DOI：10.1021/acs.orglett.9b02204

  日期：2019.8.2

  constructing all-carbon quaternary structural units from aryl ketones, revealing that the entire process involves three consecutive chemical events, namely nucleophilic addition, Meinwald 1,2-hydrogen migration, and alkylation. Interestingly, dimerization of acetophenones results in formation of 2,4-diarylfurans under the employed conditions rather than the quaternary carbon products.

  在生物分子和药物中普遍存在的苄基全碳四元立体中心的构建是具有高度实际意义的任务。在这里，我们公开了一种由芳基酮构建全碳四元结构单元的高效一锅法，揭示了整个过程涉及三个连续的化学事件，即亲核加成，Meinwald 1,2-氢迁移和烷基化。有趣的是，在所采用的条件下，苯乙酮的二聚作用导致形成2，4-二芳基呋喃，而不是季碳产物。
• Acetylenic cyanoenones as therapeutics for inflammation and carcinogenesis
  申请人：Honda Tadashi

  公开号：US10233146B2

  公开（公告）日：2019-03-19

  The present invention provides a compound having the structure: wherein X is C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, cyano, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkenylaryl, alkenylheteroaryl, alkynylaryl, alkynylheteroaryl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, heteroaryloxy, acyl, alkylhydroxy, alkylamino, alkenylamino, alkynylamino, amido, carboxyl, or carboxyl ester, or forms an unsubstituted or substituted cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indane or tetralin with Y, Y is H or forms an unsubstituted or substituted cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indane or tetralin with X, or forms an unsubstituted or substituted monocycle with Z; and Z is H or forms an unsubstituted or substituted monocycle with Y; wherein when X and Y are both H, then X is C2 alkenyl or C2 alkynyl, and when Y is H forms a substituted cyclohexyl, cycloheptyl with X, the cyclohexyl is other than a trisubstituted cyclohexyl bearing CH3, i-Pr and (CH2)2CO2CH3 groups or CH3, i-Pr and (CH2)3NH2, or a salt or ester thereof.

  本发明提供了一种具有以下结构的化合物： 其中 X是C1-C12烷基、C2-C12烯基、C2-C12炔基、氰基、芳基、杂芳基、烷芳基、烷基异芳基、烯芳基、烯基异芳基、炔芳基、炔基异芳基、烷氧基、烯氧基、炔氧基、芳氧基、杂芳氧基、酰基、烷基羟基、烷基氨基、烯基氨基、炔基氨基、氨基、羧基或羧基酯，或与 Y 形成未取代或取代的环丁基、环戊基、环己基、环庚基、茚或四萘、 Y 是 H，或与 X 形成未取代或取代的环丁基、环戊基、环己基、环庚基、茚满或四萘，或与 Z 形成未取代或取代的单环；和 Z 是 H，或与 Y 形成未取代或取代的单环； 其中，当 X 和 Y 均为 H 时，则 X 为 C2 烯基或 C2 炔基，而当 Y 为 H 时，则与 X 形成取代的环己基、环庚基，该环己基是三取代的环己基以外的环己基。 当 Y 为 H 与 X 形成取代的环己基、环庚基时，环己基不是含有 CH3、i-Pr 和 (CH2)2CO2CH3 基团或 CH3、i-Pr 和 (CH2)3NH2 的三取代环己基、 或其盐或酯。
• Julia,M.; Labia,R., Bulletin de la Societe Chimique de France, 1972, p. 4151 - 4157
  作者：Julia,M.、Labia,R.

  DOI：——

  日期：——
• Julia,M.; Mansuy,D., Bulletin de la Societe Chimique de France, 1972, p. 2684 - 2689
  作者：Julia,M.、Mansuy,D.

  DOI：——

  日期：——