2-(6,6-dimethyl-4-phenyl-5,6-dihydro-4H-1,2-oxazin-3-ylmethyl)malonic acid dimethyl ester | 742062-67-5

• 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: 2-(6,6-dimethyl-4-phenyl-5,6-dihydro-4H-1,2-oxazin-3-ylmethyl)malonic acid dimethyl ester
• 英文别名: dimethyl 2-[(6,6-dimethyl-4-phenyl-5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonate；Dimethyl 2-[(6,6-dimethyl-4-phenyl-4,5-dihydrooxazin-3-yl)methyl]propanedioate
• CAS: 742062-67-5
• 化学式: C₁₈H₂₃NO₅
• 分子量: 333.384
• InChiKey: WIQPIOOCDHWRBU-UHFFFAOYSA-N

物化性质

• 沸点：
  434.8±55.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(6,6-dimethyl-4-phenyl-5,6-dihydro-4H-1,2-oxazin-3-ylmethyl)malonic acid dimethyl ester 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 反应 0.33h， 以76%的产率得到dimethyl 2-{[(3SR,4SR)-6,6-dimethyl-4-phenyltetrahydro-2H-1,2-oxazin-3-yl]methyl}malonate
  参考文献：
  名称：

  通过C3官能化的5,6-二氢-4H-1,2-恶嗪从硝基乙烷合成取代的5-（3-羟丙基）吡咯烷-2-酮和吡咯烷二酮：一种抗抑郁剂咯利普兰的新方法

  摘要：

  容易获得[（5,6-二氢-4- ħ -1,2-恶嗪-3-基）甲基]丙二酸酯1转化成取代的5-（3-羟丙基）吡咯烷-2-酮2和pyrrolizidinones 3，这是用于有机和生物有机化学的多功能产品和中间体。所建议的合成序列包括对肟基片段的立体选择性两步还原，然后进行涉及CO 2 Me基团之一的分子内环化和最后阶段的脱羧。该策略的有效性通过吡咯嗪酮rac - 4（一种高效的抗抑郁药物来利普兰的类似物）从硝基乙烷的立体选择性合成得到证明。 5,6-二氢-4 H -1,2-恶嗪-还原-吡咯烷酮-吡咯烷酮-咯利普兰

  DOI：

  10.1055/s-0029-1216806
• 作为产物：
  描述：

  苯,(2-硝基-1-丙烯基)-,(E)- 在 三甲基溴硅烷 、 potassium tert-butylate 、 四氯化锡 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.08h， 生成 2-(6,6-dimethyl-4-phenyl-5,6-dihydro-4H-1,2-oxazin-3-ylmethyl)malonic acid dimethyl ester
  参考文献：
  名称：

  从硝基乙烷合成 3-取代的 5,6-二氢-4H-1,2-恶嗪的简便方法

  摘要：

  描述了一种从硝基乙烷合成 C-3-官能化 5,6-二氢-4H-1,2-恶嗪的新型高效四步法。包括制备3-甲基取代的六元环状硝酸酯、3-(溴甲基)-取代的5,6-二氢-4H-1,2-恶嗪中间体、溴的亲核取代。来自硝基乙烷的目标 C-3-官能化恶嗪的总产率为 15-30%。

  DOI：

  10.1055/s-2006-958930

文献信息

• A Convenient Procedure for the Synthesis of <i>N</i>-Acetyl-5,6-dihydro-2<i>H</i>-1,2-oxazines
  作者：Alexey Lesiv、Sema Ioffe、Pavel Ivashkin、Alexey Sukhorukov、Oleg Eliseev、Yulja Khomutova

  DOI：10.1055/s-2007-990857

  日期：2007.11

  Acetylation of 5,6-dihydro-4H-1,2-oxazines with an acetyl bromide/acetic anhydride mixture provides a general and quite simple procedure for the synthesis of N-acetyl-5,6-dihydro-2H-1,2-oxazines.

  乙酰溴/乙酸酐混合物对5,6-二氢-4H-1,2-噁嗪进行乙酰化反应，提供了一种通用且颇为简单的N-乙酰-5,6-二氢-2H-1,2-噁嗪合成方法。
• Diastereoselective Synthesis of γ-Amino Acids and Their Derivatives from Nitroethane via Intermediacy of 5,6-Dihydro-4<i>H</i>-1,2-oxazines Bearing the CH₂CH(CO₂Me)₂ Substituent at C3
  作者：Sema Ioffe、Alexey Sukhorukov、Alexey Lesiv、Yulia Khomutova

  DOI：10.1055/s-0028-1083360

  日期：——

  Stereoselective two-step reduction of available 2-[(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates provides an efficient route to derivatives of different γ-amino acids. The mechanism and stereochemistry of the first step, reduction of the C=N bond with sodium cyanoborohydride, is discussed. 5,6-dihydro-4H-1,2-oxazines - reduction - γ-amino acids - oxyiminium cations

  可用的2-[（（5,6-二氢-4 H -1,2-恶嗪-3-基）甲基]丙二酸酯）的立体选择性两步还原提供了一种有效的途径来制备不同的γ-氨基酸的衍生物。讨论了第一步的机理和立体化学，即用氰基硼氢化钠还原C = N键。 5,6-二氢-4 H -1,2-恶嗪-还原-γ-氨基酸-氧亚胺阳离子
• 5,6-Dihydro-4<i>H</i>-1,2-oxazines in Organic Synthesis: Catalytic Hydrogenation of [(5,6-Dihydro-4<i>H</i>-1,2-oxazin-3-yl)methyl]malonates to Methyl 7-Oxo-1-oxa-6-azaspiro[4.4]nonane-8-carboxylates
  作者：Alexey Lesiv、Sema Ioffe、Alexey Sukhorukov、Yulia Khomutova、Yulia Nelyubina

  DOI：10.1055/s-2008-106003

  日期：2008.4

  [(5,6-Dihydro-4 H-1,2-oxazin-3-yl)methyl]malonates undergo a cascade transformation into substituted methyl 7-oxo-1-oxa-6-azaspiro[4.4]nonane-8-carboxylates under catalytic hydrogenation conditions over Raney nickel. A mechanistic scheme involving initial N-O bond cleavage with the formation of imines as key intermediates is suggested.

  [(5,6-Dihydro-4 H-1,2-oxazin-3-yl)methyl]丙二酸酯经过级联转化为取代的 7-oxo-1-oxa-6-azaspiro[4.4]nonane-8-carboxylates在雷尼镍催化加氢条件下。提出了一种涉及初始 NO 键断裂并形成亚胺作为关键中间体的机制方案。
• Klenov, Michael S.; Lesiv, Alexey V.; Khomutova, Yulya A., Synthesis, 2004, # 8, p. 1159 - 1170
  作者：Klenov, Michael S.、Lesiv, Alexey V.、Khomutova, Yulya A.、Nesterov, Ivan D.、Ioffe, Sema L.

  DOI：——

  日期：——
• Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase
  作者：Alexey Yu. Sukhorukov、Anilkumar C. Nirvanappa、Jagadish Swamy、Sema L. Ioffe、Shivananju Nanjunda Swamy、Basappa、Kanchugarakoppal S. Rangappa

  DOI：10.1016/j.bmcl.2014.05.040

  日期：2014.8

  Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethy1-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 mu M, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of -1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (logP = 2.66), suggesting a potential ability to penetrate the blood-brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer's agents. (C) 2014 Elsevier Ltd. All rights reserved.