(1S)-1-methyl-2-oxo-cyclohexanecarboxylic acid ethyl ester | 152614-56-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S)-1-methyl-2-oxo-cyclohexanecarboxylic acid ethyl ester
• 英文别名: ethyl (1S)-1-methyl-2-oxocyclohexane-1-carboxylate
• CAS: 152614-56-7
• 化学式: C₁₀H₁₆O₃
• 分子量: 184.235
• InChiKey: JPZANUHBLDNRJV-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S)-1-methyl-2-oxo-cyclohexanecarboxylic acid ethyl ester 在 氢氧化钾 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 19.5h， 生成 (S)-1-methylcyclohex-2-enecarboxylic acid
  参考文献：
  名称：

  Evaluation of possible intramolecular [4+2] cycloaddition routes for assembling the central tetracyclic core of the potent marine antiinflammatory agent mangicol A

  摘要：

  A plan for enantioselective construction of the mangicol A framework by means of intramolecular Diels-Alder cycloaddition is outlined. First to be assembled is the enantiopure cyclopentenecarboxylic acid 16. Of the several approaches targeting the 1,3-diene component 56, only that involving palladium-catalyzed enyne cyclization proved successful. Following the coupling of 16 to 56, we were unable to bring about any detectable level of (4 pi+2 pi) cycloaddition. Activation of the diene by incorporation of an OSiEt3 substituent on a terminal sp(2)-hybridized center likewise proved unsuccessful. Further facilitation was sought in the form of cyclopentenonecarboxylate 66. However, thermal activation, Lewis acid catalysis, and high-pressure conditions proved ineffective and did not lead to C-C bond formation. These studies serve to underscore the extent to which steric complications can complicate matters and the extent to which they must be skirted to arrive at the title compound. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.11.096
• 作为产物：
  描述：

  2-carbethoxy-2-methylcyclohexanone 生成 (1S)-1-methyl-2-oxo-cyclohexanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Ple-catalyzed resolution of α-substituted β-ketoesters application to the synthesis of (+)-nitraniine and (−)-Isonitramine

  摘要：

  Substituted beta-Ketoesters can be prepared in enantiomerically pure form by pig liver esterase catalyzed hydrolysis of their racemic precursors. With the asymmetric carbon atom possessing a quaternary centre, (+)-Nitramine and (-)-Isonitramine have been synthesized.

  DOI：

  10.1016/s0957-4166(00)80054-3

文献信息

• Tandem Decarboxylative Cyclization/Alkenylation Strategy for Total Syntheses of (+)-Longirabdiol, (−)-Longirabdolactone, and (−)-Effusin
  作者：Jianpeng Zhang、Zijian Li、Junming Zhuo、Yue Cui、Ting Han、Chao Li

  DOI：10.1021/jacs.9b03978

  日期：2019.5.22

  Structurally complex and bioactive ent-kaurane diterpenoids have well-characterized biological functions and have drawn widespread attention from chemists for many decades. However, construction of highly oxidized forms of such diterpenoids still presents considerable challenges to synthetic chemists. Herein, we report the first total syntheses of C19 oxygenated spiro-lactone ent-kauranoids, including

  结构复杂且具有生物活性的 ent-kaurane 二萜类化合物具有良好的生物学功能，几十年来一直受到化学家的广泛关注。然而，构建此类二萜类化合物的高度氧化形式仍然对合成化学家提出了相当大的挑战。在此，我们报告了 C19 含氧螺内酯 ent-kauranoids 的首次全合成，包括 longirabdiol、longirabdolactone 和 effusin。通过三个基于自由基的反应实现了用于所有三种合成的通用中间体的简明合成：（1）新设计的串联脱羧环化/烯基化序列，该序列与邻位烯基化同时形成顺式 19，6-内酯， (2) Ni催化的脱羧Giese反应，立体选择性地构建C10季铵，(3) 乙烯基自由基环化产生刚性双环[3.2.1]辛烷。来自共同中间体的一系列后期氧化依次提供每种天然产物。对这些合成天然产物的进一步生物学评估揭示了广泛的抗癌活性。
• Development of a Scalable Synthesis toward a KRAS G12C Inhibitor Building Block Bearing an All-Carbon Quaternary Stereocenter, Part 1: From Discovery Route to Kilogram-Scale Production
  作者：Joyce C. Leung、Yibo Xu、Suttipol Radomkit、Jaehee Lee、Wan Shin Kim、Jonathan T. Reeves、Weitong Dong、Hwanjong Jang、Xiaowen Hou、Jon C. Lorenz、Xiaole Shao、Denis Byrne、Joe Johnson、Anthony Brundage、Clement Valentin、Phouvieng Beyer、Susan V. DiMeo、Bo Qu、Ruoshi Li、Max Sarvestani、Jinhua J. Song

  DOI：10.1021/acs.oprd.3c00362

  日期：2024.1.19

  Synthesis of molecules containing all-carbon quaternary stereocenters has been a longstanding challenge in organic chemistry. In one of our discovery oncology programs, a key chiral building block bearing an all-carbon quaternary chiral center was of particular interest and was later identified as a core structure for a KRAS G12C inhibitor. Herein, the development of a safer and practical route to

  含有全碳四元立构中心的分子的合成一直是有机化学领域的长期挑战。在我们的一个发现肿瘤学项目中，具有全碳四元手性中心的关键手性结构单元受到特别关注，后来被确定为 KRAS G12C 抑制剂的核心结构。在此，描述了通往关键构建块1的更安全且实用的路线的开发。通过取代涉及使用高能试剂和广泛色谱纯化的工艺，开发了一种利用化学拆分的可扩展工艺，以获取千克数量的手性构件，从而能够及时交付用于临床前和临床研究的 API。
• Evaluation of possible intramolecular [4+2] cycloaddition routes for assembling the central tetracyclic core of the potent marine antiinflammatory agent mangicol A
  作者：Stefan Pichlmair、Manuel de Lera Ruiz、Kallol Basu、Leo A. Paquette

  DOI：10.1016/j.tet.2005.11.096

  日期：2006.5

  A plan for enantioselective construction of the mangicol A framework by means of intramolecular Diels-Alder cycloaddition is outlined. First to be assembled is the enantiopure cyclopentenecarboxylic acid 16. Of the several approaches targeting the 1,3-diene component 56, only that involving palladium-catalyzed enyne cyclization proved successful. Following the coupling of 16 to 56, we were unable to bring about any detectable level of (4 pi+2 pi) cycloaddition. Activation of the diene by incorporation of an OSiEt3 substituent on a terminal sp(2)-hybridized center likewise proved unsuccessful. Further facilitation was sought in the form of cyclopentenonecarboxylate 66. However, thermal activation, Lewis acid catalysis, and high-pressure conditions proved ineffective and did not lead to C-C bond formation. These studies serve to underscore the extent to which steric complications can complicate matters and the extent to which they must be skirted to arrive at the title compound. (c) 2006 Elsevier Ltd. All rights reserved.
• Ple-catalyzed resolution of α-substituted β-ketoesters application to the synthesis of (+)-nitraniine and (−)-Isonitramine
  作者：Bernhard Westermann、Hildegard Große Scharmann、Ina Kortmann

  DOI：10.1016/s0957-4166(00)80054-3

  日期：1993.10

  Substituted beta-Ketoesters can be prepared in enantiomerically pure form by pig liver esterase catalyzed hydrolysis of their racemic precursors. With the asymmetric carbon atom possessing a quaternary centre, (+)-Nitramine and (-)-Isonitramine have been synthesized.