ethyl (S)-1-methyl-2-oxocyclopentane-1-carboxylate | 72763-85-0

• 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: ethyl (S)-1-methyl-2-oxocyclopentane-1-carboxylate
• 英文别名: (S)-ethyl 1-methyl-2-oxocyclopentanecarboxylate；ethyl (1S)-1-methyl-2-oxocyclopentane-1-carboxylate
• CAS: 72763-85-0
• 化学式: C₉H₁₄O₃
• 分子量: 170.208
• InChiKey: UIZCVGDHOSROCR-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 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：

  ethyl (S)-1-methyl-2-oxocyclopentane-1-carboxylate 在 二异丁基氢化铝 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 (S)-2-((tert-butyldimethylsilyl)oxy)-1-methylcyclopent-2-enecarbaldehyde
  参考文献：
  名称：

  Helenalin启发的双亲电子试剂靶向NF-κBp65

  摘要：

  规范的NF-κB信号传导途径是细胞炎症反应的介体，也是开发多种人类疾病疗法的靶标。尽管已知有大量化合物抑制激活途径中的上游蛋白，但该途径中最远的下游蛋白p50 / p65转录因子异二聚体对小分子抑制具有顽固性。鉴于许多上游蛋白在多种生化途径中的作用，靶向p50 / p65异二聚体提供了提高靶点特异性的机会。为此，p65蛋白在其DNA结合界面上存在两个非二硫键半胱氨酸，Cys38和Cys120，它们可被共价分子靶向。天然产物helenalin，倍半萜内酯，先前已显示出可将Cys38靶向p65并消除其DNA结合能力。利用海伦纳林作为灵感，设计，合成了简化的海伦纳林类似物，并显示了其在细胞培养物中抑制诱导的经典NF-κB信号传导的作用。此外，两个简化的海伦素探针擅长形成共价蛋白加合物，与重组p65上的Cys38结合，并靶向HeLa细胞中的p65，而不会参与经典的NF-κB信号蛋白IκBα，p50

  DOI：

  10.1021/acschembio.6b00751
• 作为产物：
  描述：

  1-甲基-2-氧代环戊烷-1-羧酸乙酯 以72%的产率得到ethyl (S)-1-methyl-2-oxocyclopentane-1-carboxylate
  参考文献：
  名称：

  Chiral Synthesis via Organoboranes. 42. Selective Reductions. 57. Efficient Kinetic Resolution of Representative α-Tertiary Ketones with B-Chlorodiisopinocampheylborane

  摘要：

  Kinetic resolution of racemic alpha-tertiary ketones with 0.5-0.6 molar equiv of B-chlorodiisopinocampheylborane provides the product alcohols in very high diastereomeric and enantiomeric excess, with the unreacted ketone recovered in very high ee. For example, ethyl 1-methyl-8-oxocyclopentane- and -cyclohexanecarboxylates are partially reduced to recover the ketone in 91 greater than or equal to 99% ee and the product alcohols in up to 94% de, with >90% ee for the major diastereomer. Bicyclic ketones, such as 1-methyl- and 1-ethylnorcamphor, camphor, and camphenilone, are readily resolved to provide the ketone in 92 to greater than or equal to 99% ee, with the product alcohol recovered in high de and ee. Dihydrospiro[bicyclo[3.2.1]octane-2,2'(3'H)-furan]-3-one is resolved to provide the ketone in greater than or equal to 99% ee and the product alcohol in greater than or equal to 99% de. In all the cases studied, the R-isomer of the ketone is recovered when (d)Ipc(2)BCl is used for kinetic resolution, while (l)Ipc(2)BCl provides the S-ketone. Optimum conditions for obtaining the product alcohol, or the ketone, or both, in very high yields and ee have been established.

  DOI：

  10.1021/jo951206z

文献信息

• Chiral Synthesis via Organoboranes. 43. Selective Reductions. 58. Reagent-Controlled Diastereoselective Reduction of (+)- and <b>(</b><b>−</b><b>)-</b>α-Chiral Ketones with (+)- and (−)-<i>B</i>-Chlorodiisopinocampheylborane
  作者：P. Veeraraghavan Ramachandran、Guang-Ming Chen、Herbert C. Brown

  DOI：10.1021/jo951207r

  日期：1996.1.1

  Asymmetric reduction of (+)- and (-)-alpha-chiral ketones with (+)- and (-)-B-chlorodiisopinocampheylborane provides the product alcohols in very high diastereomeric excess, with the matched pairs providing >100:1 selectivity and the mismatched pairs showing 4:1-15:1 selectivity. The high selectivity achieved even in the mismatched pairs reveals the power of the reagent to control the stereochemical outcome. The rates of the reaction of the matched pairs are faster than those of the mismatched pairs, In all the cases studied thus far, the (-)-reagent ((d)Ipc(2)BCl) and (S)ketone or the (+)-reagent ((l)Ipc(2)BCl) and (R)-ketone constitute matched pairs and the (-)-reagent and (R)-ketone or the (+)-reagent and (S)-ketone constitute mismatched pairs, A possible mechanism for the reductions is discussed.
• Construction of All-Carbon Quaternary Center by R₂AlCl−Mediated Ring-Opening Reaction of Oxacycles
  作者：Chao Che、Lianzhu Liu、Jianxian Gong、Yunfang Yang、Guoxin Wang、Junmin Quan、Zhen Yang

  DOI：10.1021/ol902685h

  日期：2010.2.5

  An unexpected R2AlCl-mediated ring-opening reaction of oxacycles for the formation of all-carbon quaternary centers was discovered, and a possible mechanism is proposed. The developed chemistry provides a concise approach to synthesize structural diverse of dolastane-type compounds.
• Chemo-enzymatic synthesis of ( R )-5-hydroxymethyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate, a potential chiral building block for multicyclic terpenoids
  作者：Kazuaki Kuwata、Kengo Hanaya、Takeshi Sugai、Mitsuru Shoji

  DOI：10.1016/j.tetasy.2017.05.007

  日期：2017.7

  The chemo-enzymatic synthesis of (R)-5-hydroxymethy1-2-isopropyl-5-methylcyclopent-1-en-1-y1 trifluoromethylsulfonate, a potential chiral building block for polycyclic terpenoids containing a five-membered ring having isopropyl and angular methyl substituents, such as erinacin A and dolatriol, was achieved over 11 steps from ethyl 2-oxocyclopentane-l-carboxylate. The key synthetic precursor for this triflate was ethyl (1S,2R)-2-hydroxycyclopentanecarboxylate (>99% ee), which was prepared by a lipase-catalyzed enantioselective hydrolysis of the corresponding racemic acetate. The antipodal (S)-triflate is expected to be the synthetic intermediate for another group of terpenoids involving hamigeran B and stolonidiol. Enantiomerically pure (1R,2S)-hydroxyester (>99% ee) was prepared in high yield using the asymmetric reduction of the oxoester with commercially available carbonyl reductase, "Chiralscreen (R) OH"-E001. (C) 2017 Elsevier Ltd. All rights reserved.
• Targeting NF-κB p65 with a Helenalin Inspired Bis-electrophile
  作者：John C. Widen、Aaron M. Kempema、Peter W. Villalta、Daniel A. Harki

  DOI：10.1021/acschembio.6b00751

  日期：2017.1.20

  by covalent molecules. The natural product helenalin, a sesquiterpene lactone, has been previously shown to target Cys38 on p65 and ablate its DNA-binding ability. Using helenalin as inspiration, simplified helenalin analogues were designed, synthesized, and shown to inhibit induced canonical NF-κB signaling in cell culture. Moreover, two simplified helenalin probes were proficient at forming covalent

  规范的NF-κB信号传导途径是细胞炎症反应的介体，也是开发多种人类疾病疗法的靶标。尽管已知有大量化合物抑制激活途径中的上游蛋白，但该途径中最远的下游蛋白p50 / p65转录因子异二聚体对小分子抑制具有顽固性。鉴于许多上游蛋白在多种生化途径中的作用，靶向p50 / p65异二聚体提供了提高靶点特异性的机会。为此，p65蛋白在其DNA结合界面上存在两个非二硫键半胱氨酸，Cys38和Cys120，它们可被共价分子靶向。天然产物helenalin，倍半萜内酯，先前已显示出可将Cys38靶向p65并消除其DNA结合能力。利用海伦纳林作为灵感，设计，合成了简化的海伦纳林类似物，并显示了其在细胞培养物中抑制诱导的经典NF-κB信号传导的作用。此外，两个简化的海伦素探针擅长形成共价蛋白加合物，与重组p65上的Cys38结合，并靶向HeLa细胞中的p65，而不会参与经典的NF-κB信号蛋白IκBα，p50
• Chiral Synthesis via Organoboranes. 42. Selective Reductions. 57. Efficient Kinetic Resolution of Representative α-Tertiary Ketones with <i>B</i>-Chlorodiisopinocampheylborane
  作者：P. Veeraraghavan Ramachandran、Guang-Ming Chen、Herbert C. Brown

  DOI：10.1021/jo951206z

  日期：1996.1.1

  Kinetic resolution of racemic alpha-tertiary ketones with 0.5-0.6 molar equiv of B-chlorodiisopinocampheylborane provides the product alcohols in very high diastereomeric and enantiomeric excess, with the unreacted ketone recovered in very high ee. For example, ethyl 1-methyl-8-oxocyclopentane- and -cyclohexanecarboxylates are partially reduced to recover the ketone in 91 greater than or equal to 99% ee and the product alcohols in up to 94% de, with >90% ee for the major diastereomer. Bicyclic ketones, such as 1-methyl- and 1-ethylnorcamphor, camphor, and camphenilone, are readily resolved to provide the ketone in 92 to greater than or equal to 99% ee, with the product alcohol recovered in high de and ee. Dihydrospiro[bicyclo[3.2.1]octane-2,2'(3'H)-furan]-3-one is resolved to provide the ketone in greater than or equal to 99% ee and the product alcohol in greater than or equal to 99% de. In all the cases studied, the R-isomer of the ketone is recovered when (d)Ipc(2)BCl is used for kinetic resolution, while (l)Ipc(2)BCl provides the S-ketone. Optimum conditions for obtaining the product alcohol, or the ketone, or both, in very high yields and ee have been established.