4-methoxycyclohex-2-en-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-methoxycyclohex-2-en-1-one
• 英文别名: 4-Methoxycyclohex-2-en-1-one
• 化学式: C₇H₁₀O₂
• 分子量: 126.155
• InChiKey: AWRPMEPPVWAWBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methoxycyclohex-2-en-1-one 在 ammonium acetate 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 tert-butyl ((3aR*,4R*,7R*,7aS*)-2-benzyl-7-methoxyoctahydro-1H-isoindol-4-yl)carbamate
  参考文献：
  名称：

  发现和优化具有抗氟喹诺酮抗革兰氏阳性细菌活性的DNA促旋酶和拓扑异构酶IV抑制剂。

  摘要：

  本文中，我们描述了通过结合和稳定DNA裂解复合物抑制细菌DNA促旋酶和拓扑异构酶IV的新系列的发现和优化。该系列产品的优化导致化合物25的鉴定，该化合物对革兰氏阳性细菌具有强效活性，良好的体外安全性和出色的体内药代动力学特性。在小鼠大腿模型中，发现化合物25对氟喹诺酮敏感的金黄色葡萄球菌感染有效，其剂量低于莫西沙星。肺炎克雷伯菌的拓扑异构酶IV形成的三元复合物的X射线晶体结构，化合物25和切割的DNA表示该化合物不参与水-金属离子桥相互作用，也不与喹诺酮抗性确定区域（QRDR）中的残基形成直接接触。这表明与氟喹诺酮类药物相比，QRDR突变对25种抗菌活性的影响降低的结构基础。

  DOI：

  10.1021/acs.jmedchem.1c00375
• 作为产物：
  描述：

  4-羟基环己酮乙二醇缩醛 在 potassium tert-butylate 、 pyridinium hydrobromide perbromide 、 草酸 、 silica gel 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 4.5h， 生成 4-methoxycyclohex-2-en-1-one
  参考文献：
  名称：

  Stereospecific Retro-Diels-Alder fragmentation of stereoisomeric 3-methoxy- and 3,6-dialkoxytricyclo[6.2.2.02,7]dodeca-9-enes upon electron ionization

  摘要：

  The stereoisomeric 2,3-cis- and 2,3-trans-3-methoxytricyclo[6.2.2.0(2,7)]dodeca-9-enes endo-1 and exo-1 (endo and exo refer to the methoxy group) exhibit different behavior under electron ionization (EI): the m/z 80 cyclohexa-1,3-diene radical cation formed by retro-Diels-Alder (RDA) fragmentation is the most abundant ion in the 70 eV mass spectrum of endo-1, whereas exo-1 exhibits preferential formation of an m/z 111 ion corresponding to the O-methylcyclohex-2-en-1-one structure (ion a), which may be obtained by an RDA fragmentation accompanied by a hydrogen migration (RDA - H), with the charge retained in the dienophile moiety. A similar effect has been observed in the EI mass spectra of the four stereoisomeric 3-ethoxy-6-methoxytricyclo [6.2.2.0(2,7)] dodeca-9-enes 2; endo-2, with both endo-alkoxy groups, gives rise to the most abundant mit 80 ion via the regular RDA process, whereas the other three stereoisomers, with at least one exo-alkoxy group, afford the most abundant m/z 155 ions via the RDA -H process, which correspond to the 4-alkoxy-substituted analogues of the mit 111 ion a obtained from exo-1. Collision-induced dissociation measurements and a deuterium labeling study showed that che mit 155 ions obtained from the two trans-diethers (trans-2a and trans-2b) have isomeric structures b and c (a mixture of b and c is formed in the case of exo-2), and that the highly stereospecific RDA -H process involves a double hydrogen transfer, one from position 4 to the diene moiety and the other from position 3 to 4. The above stereospecific behavior shows that the thermodynamically favored RDA -H process has a higher activation energy than the regular RDA fragmentation in the case of endo-1 and endo-2. In all other isomers, which have at least one exo-alkoxyl, the activation energy of the KDA -H process is lower than that of RDA. The latter effect is ascribed to anchimeric assistance of the alkoxyl in the initial C-C bond cleavage in the stepwise RDA -H process, which is possible only when at least one alkoxyl has the exo configuration. (C) 1998 John Wiley & Sons, Ltd.

  DOI：

  10.1002/(sici)1096-9888(199803)33:3<229::aid-jms632>3.0.co;2-b

文献信息

• Ene Reductase Enabled Intramolecular β‐C−H Functionalization of Substituted Cyclohexanones for Efficient Synthesis of Bridged Bicyclic Nitrogen Scaffolds
  作者：Guangde Jiang、Chunshuai Huang、Wesley Harrison、Hongxiang Li、Megan Zhou、Huimin Zhao

  DOI：10.1002/anie.202302125

  日期：2023.5.22

  An unprecedented β-C−H functionalization reaction that is enabled by ene reductases is reported. When the reaction is coupled with photocatalysis, various 6-azabicyclo[3.2.1]octan-3-ones can be synthesized in a straightforward manner from readily available cyclohexenones and N-phenylglycines. This chemoenzymatic reaction can be carried out on a gram scale, and the product can be further selectively

  据报道，烯还原酶引发了前所未有的 β-C−H 功能化反应。当该反应与光催化结合时，可以从容易获得的环己烯酮和N-苯基甘氨酸以直接的方式合成各种6-氮杂双环[3.2.1]辛烷-3-酮。这种化学酶促反应可以在克级进行，并且产物可以进一步选择性衍生化。
• Tungsten-Catalyzed Heterocycloisomerization Approach to 4,5-Dihydro-benzo[<i>b</i>]furans and -indoles
  作者：Ethan L. Fisher、Sidney M. Wilkerson-Hill、Richmond Sarpong

  DOI：10.1021/ja3045647

  日期：2012.6.20

  A W(CO)(5).THF-catalyzed cycloisomerization of bicyclo[4.1.0] substrates to afford mono C4-substituted 4,5-dihydro-benzo[b]furans and -indoles is reported. The title compounds are versatile intermediates that lead to a range of fused bicycles including the cores of various furan-, benzofuran-, and indole-containing natural products. In many cases, the functionalization of the dihydro-benzo[b]furans and -indoles is orthogonal to that of the corresponding benzofurans and indoles and, thus, offers complementary approaches for synthesis.
• METHODS OF IMPROVING PRODUCTION OF MORPHINAN ALKALOIDS AND DERIVATIVES
  申请人：Antheia, Inc.

  公开号：US20220162656A1

  公开（公告）日：2022-05-26

  Methods and systems are provided for producing codeinone within an engineered non-plant cell. The method comprises, within the engineered non-plant cell, producing a thebaine product. The method also comprises, within the engineered non-plant cell, contacting the thebaine product with an enzyme having thebaine 6-O-demethylase activity, thereby producing a neopinone product. Additionally, the method comprises, within the engineered non-plant cell, contacting the neopinone product with a neopinone isomerase, thereby producing a codeinone product.
• Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria
  作者：Guillaume Lapointe、Colin K. Skepper、Lauren M. Holder、Duncan Armstrong、Cornelia Bellamacina、Johanne Blais、Dirksen Bussiere、Jianwei Bian、Cody Cepura、Helen Chan、Charles R. Dean、Gianfranco De Pascale、Bhavesh Dhumale、L. Mark Fisher、Mangesh Fulsunder、Bhavin Kantariya、Julie Kim、Sean King、Lauren Kossy、Upendra Kulkarni、Jay Lakshman、Jennifer A. Leeds、Xiaolan Ling、Anatoli Lvov、Sylvia Ma、Swapnil Malekar、David McKenney、Wosenu Mergo、Louis Metzger、Keshav Mhaske、Heinz E. Moser、Mina Mostafavi、Sunil Namballa、Jonas Noeske、Colin Osborne、Ashish Patel、Darshit Patel、Tushar Patel、Philippe Piechon、Valery Polyakov、Krunal Prajapati、Katherine R. Prosen、Folkert Reck、Daryl L. Richie、Mark R. Sanderson、Shailesh Satasia、Bhautik Savani、Jogitha Selvarajah、Vijay Sethuraman、Wei Shu、Kyuto Tashiro、Katherine V. Thompson、Krishniah Vaarla、Lakhan Vala、Dennis A. Veselkov、Jason Vo、Bhavesh Vora、Trixie Wagner、Laura Wedel、Sarah L. Williams、Satya Yendluri、Qin Yue、Aregahegn Yifru、Yong Zhang、Alexey Rivkin

  DOI：10.1021/acs.jmedchem.1c00375

  日期：2021.5.13

  Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV via binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compound 25, which has potent activity against Gram-positive bacteria, a favorable in vitro safety profile, and excellent in vivo pharmacokinetic properties

  本文中，我们描述了通过结合和稳定DNA裂解复合物抑制细菌DNA促旋酶和拓扑异构酶IV的新系列的发现和优化。该系列产品的优化导致化合物25的鉴定，该化合物对革兰氏阳性细菌具有强效活性，良好的体外安全性和出色的体内药代动力学特性。在小鼠大腿模型中，发现化合物25对氟喹诺酮敏感的金黄色葡萄球菌感染有效，其剂量低于莫西沙星。肺炎克雷伯菌的拓扑异构酶IV形成的三元复合物的X射线晶体结构，化合物25和切割的DNA表示该化合物不参与水-金属离子桥相互作用，也不与喹诺酮抗性确定区域（QRDR）中的残基形成直接接触。这表明与氟喹诺酮类药物相比，QRDR突变对25种抗菌活性的影响降低的结构基础。
• Stereospecific Retro-Diels-Alder fragmentation of stereoisomeric 3-methoxy- and 3,6-dialkoxytricyclo[6.2.2.02,7]dodeca-9-enes upon electron ionization
  作者：N. Morlender-Vais、A. Mandelbaum

  DOI：10.1002/(sici)1096-9888(199803)33:3<229::aid-jms632>3.0.co;2-b

  日期：1998.3

  The stereoisomeric 2,3-cis- and 2,3-trans-3-methoxytricyclo[6.2.2.0(2,7)]dodeca-9-enes endo-1 and exo-1 (endo and exo refer to the methoxy group) exhibit different behavior under electron ionization (EI): the m/z 80 cyclohexa-1,3-diene radical cation formed by retro-Diels-Alder (RDA) fragmentation is the most abundant ion in the 70 eV mass spectrum of endo-1, whereas exo-1 exhibits preferential formation of an m/z 111 ion corresponding to the O-methylcyclohex-2-en-1-one structure (ion a), which may be obtained by an RDA fragmentation accompanied by a hydrogen migration (RDA - H), with the charge retained in the dienophile moiety. A similar effect has been observed in the EI mass spectra of the four stereoisomeric 3-ethoxy-6-methoxytricyclo [6.2.2.0(2,7)] dodeca-9-enes 2; endo-2, with both endo-alkoxy groups, gives rise to the most abundant mit 80 ion via the regular RDA process, whereas the other three stereoisomers, with at least one exo-alkoxy group, afford the most abundant m/z 155 ions via the RDA -H process, which correspond to the 4-alkoxy-substituted analogues of the mit 111 ion a obtained from exo-1. Collision-induced dissociation measurements and a deuterium labeling study showed that che mit 155 ions obtained from the two trans-diethers (trans-2a and trans-2b) have isomeric structures b and c (a mixture of b and c is formed in the case of exo-2), and that the highly stereospecific RDA -H process involves a double hydrogen transfer, one from position 4 to the diene moiety and the other from position 3 to 4. The above stereospecific behavior shows that the thermodynamically favored RDA -H process has a higher activation energy than the regular RDA fragmentation in the case of endo-1 and endo-2. In all other isomers, which have at least one exo-alkoxyl, the activation energy of the KDA -H process is lower than that of RDA. The latter effect is ascribed to anchimeric assistance of the alkoxyl in the initial C-C bond cleavage in the stepwise RDA -H process, which is possible only when at least one alkoxyl has the exo configuration. (C) 1998 John Wiley & Sons, Ltd.