tert-butyl 2-oxo-6-phenylhexanoate | 1361018-53-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: tert-butyl 2-oxo-6-phenylhexanoate
• CAS: 1361018-53-2
• 化学式: C₁₆H₂₂O₃
• 分子量: 262.349
• InChiKey: JPAQVMDPEBJNHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  19.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-oxo-6-phenylhexanoate 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-oxo-N-phenethyl-6-phenylhexanamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

  摘要：

  The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified alpha-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the alpha-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.

  DOI：

  10.1021/acs.jmedchem.0c00522
• 作为产物：
  描述：

  4-苯基-1-丁基溴 在 碘 、 magnesium 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 tert-butyl 2-oxo-6-phenylhexanoate
  参考文献：
  名称：

  Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

  摘要：

  The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified alpha-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the alpha-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.

  DOI：

  10.1021/acs.jmedchem.0c00522

文献信息

• Asymmetric Organocatalytic Michael/Michael/Henry Sequence to Construct Cyclohexanes with Six Vicinal Stereogenic Centers
  作者：Xiaohua Liu、Yushuang Chen、Weiwei Luo、Lili Lin、Xiaoming Feng

  DOI：10.1055/s-0036-1588940

  日期：——

  efficient, asymmetric, catalytic, triple-cascade reaction between α-keto esters and nitroalkenes to construct cyclohexanes with six vicinal stereogenic centers in good yields and with high enantioselectivities has been established. A bifunctional guanidine–amide organocatalyst proved to be useful for the Michael/Michael/Henry sequence through Bronsted base and hydrogen-bonding cooperative catalysis.

  已经建立了一种有效的、不对称的、催化的、α-酮酯和硝基烯烃之间的三重级联反应，以高产率和高对映选择性构建具有六个邻位立体中心的环己烷。双功能胍-酰胺有机催化剂通过布朗斯台德碱和氢键协同催化被证明可用于迈克尔/迈克尔/亨利序列。
• A Highly Diastereo- and Enantioselective Reaction for Constructing Functionalized Cyclohexanes: Six Contiguous Stereocenters in One Step
  作者：Dengjian Shi、Yinjun Xie、Han Zhou、Chungu Xia、Hanmin Huang

  DOI：10.1002/anie.201107495

  日期：2012.1.27

  Just mix to get six: Six contiguous stereocenters, including one quaternary stereocenter, and three CC bonds are created by a new copper‐catalyzed tandem reaction (see scheme). Rigid chiral diamine ligands enabled this asymmetric tandem reaction to proceed with excellent stereoselectivity (complete diastereoselectivity and high enantioselectivity) and high yield under mild reaction conditions.

  只需混合即可得到六个：六价连续的立体中心（包括一个四级立体中心）和三个CC键是通过新的铜催化串联反应生成的（请参见方案）。刚性手性二胺配体使这种不对称串联反应能够在温和的反应条件下以优异的立体选择性（完全的非对映选择性和高对映选择性）和高收率进行。
• Diastereo- and enantioselective conjugate addition of α-keto esters to nitroalkenes: Complete switch in the enantioselectivity by tuning the metal center or rigidity of the ligand
  作者：Xiangning Chen、Han Zhou、Hanmin Huang

  DOI：10.1016/s1872-2067(14)60199-6

  日期：2015.1

  been developed to control the dual enantioselectivity of the conjugate addition of α-keto esters to nitroalkenes. The use of the chiral diamine (1 S ,1’ S )-1,1′-biisoindoline as a chiral ligand with either (Cu(OAc) 2 ·H 2 O or Ni(OAc) 2 ·4H 2 O as the catalyst provide facile access to the respective enantiomers resulting from the conjugate addition reaction with high levels of enantioselectivity (94%

  摘要 已经开发了一系列有效的催化系统来控制 α-酮酯与硝基烯烃共轭加成的双重对映选择性。使用手性二胺 (1 S ,1' S )-1,1'-双异二氢吲哚作为手性配体，以 (Cu(OAc) 2 ·H 2 O 或 Ni(OAc) 2 ·4H 2 O 为催化剂)以高水平的对映选择性（94% ee vs 93% ee）轻松获得由共轭加成反应产生的各个对映异构体。此外，使用 Cu(OAc) 2 ·H 2 O 作为金属中心允许对映选择性通过调节手性二胺配体的刚性（94% ee vs 94% ee）来切换共轭加成反应。
• Water enables an asymmetric cross reaction of α-keto acids with α-keto esters for the synthesis of quaternary isotetronic acids
  作者：Ping Chen、Kai Wang、Boyu Zhang、Wengang Guo、Yan Liu、Can Li

  DOI：10.1039/c9cc06356k

  日期：——

  A water promoted asymmetric aldol/lactonization/enolization cascade reaction of α-keto acids and α-keto esters was developed, affording the first general protocol for the construction of chiral quaternary isotetronic acids with excellent enantioselectivity. Theoretical results indicate that intramolecular ionized enamine intermediates stabilized by water generate zwitterionic transition states in a

  开发了水促进的α-酮酸和α-酮酯的不对称羟醛/内酯化/烯醇化级联反应，为构造手性季戊四烯异四酸具有良好的对映选择性提供了第一个通用方案。理论结果表明，用水稳定的分子内离子化烯胺中间体在较低的活化能和较高的面部选择性下产生两性离子过渡态，从而导致较高的活性以及化学和对映体选择性。