rac-(2S,3S,4S)-2,3-epoxy-4-hexanoyloxy-5-[(2-hexanoyloxybenzoyl)amino]cyclohex-5-en-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: rac-(2S,3S,4S)-2,3-epoxy-4-hexanoyloxy-5-[(2-hexanoyloxybenzoyl)amino]cyclohex-5-en-1-one
• 英文别名: dihexanoyl rac-(2S,3S,4S)-dehydroxymethylepoxyquinomycin；2,3-epoxy-4-hexanoyloxy-5-[(2-hexanoyloxybenzoyl)amino]cyclohex-5-en-1-one；[(1R,2R,6R)-3-[(2-hexanoyloxybenzoyl)amino]-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-2-yl] hexanoate
• 化学式: C₂₅H₃₁NO₇
• 分子量: 457.524
• InChiKey: ABKWNDFMJUKOFH-TZRRMPRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  rac-(2S,3S,4S)-2,3-epoxy-4-hexanoyloxy-5-[(2-hexanoyloxybenzoyl)amino]cyclohex-5-en-1-one 在 Burkholderia cepacia lipase 、 水 作用下， 以 丙酮 为溶剂， 生成 (1R,2R,6R)-3-(2-hydroxybenzamido)-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-2-yl hexanoate 、 (-)-2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide
  参考文献：
  名称：

  Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB

  摘要：

  A new route for (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent NF-kappa B inhibitor, was established by chemoenzymatic approach. Elaboration on the asymmetric epoxidation of a p-benzoquinone monoketal with benzylcinchonidinium tert-butylhydroperoxide yielded an epoxyenone, in 79.8% ee and 57% yield in reproducible manner. By way of the transformation of this key intermediate to enantiomerically pure (2S,35,4S)-DHMEQ the contaminating undesired enantiomer could be effectively removed by applying Burkholderia cepacia lipase-catalyzed hydrolysis of diacylated precursor. The above integrated combination of chemical asymmetric synthesis and enzyme-catalyzed kinetic resolution enabled us to prepare active DHMEQ in a large-scale. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.07.013
• 作为产物：
  描述：

  2-[(2-acetoxybenzoyl)amino]cyclohexa-2,5-diene-1,4-dione 在 4-二甲氨基吡啶 、 magnesium bis(monoperoxyphthalate)hexahydrate 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 12.08h， 生成 rac-(2S,3S,4S)-2,3-epoxy-4-hexanoyloxy-5-[(2-hexanoyloxybenzoyl)amino]cyclohex-5-en-1-one
  参考文献：
  名称：

  化学酶促快速途径生成外消旋二己酰基（2R *，3R *，4R *）-脱羟甲基环氧丁香霉素（DHMEQ），脂肪酶催化的强核因子-κB抑制剂（2S，3S，4S）-DHMEQ的前体。

  摘要：

  为了大规模合成有效的核因子（NF）-κB抑制剂（2S，3S，4S）-脱羟基甲基环氧奎霉素（DHMEQ），其相应的外消旋前体二己酰基（2R *，3R *，开发了4R *）-DHMEQ。通过同时使用氢醌和苯醌中间体，可提高总收率，重现性和合成步骤，并降低合成成本。

  DOI：

  10.1248/cpb.c12-00417

文献信息

• Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB
  作者：Manabu Hamada、Yukihiro Niitsu、Chihiro Hiraoka、Ikuko Kozawa、Toshinori Higashi、Mitsuru Shoji、Kazuo Umezawa、Takeshi Sugai

  DOI：10.1016/j.tet.2010.07.013

  日期：2010.8

  A new route for (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent NF-kappa B inhibitor, was established by chemoenzymatic approach. Elaboration on the asymmetric epoxidation of a p-benzoquinone monoketal with benzylcinchonidinium tert-butylhydroperoxide yielded an epoxyenone, in 79.8% ee and 57% yield in reproducible manner. By way of the transformation of this key intermediate to enantiomerically pure (2S,35,4S)-DHMEQ the contaminating undesired enantiomer could be effectively removed by applying Burkholderia cepacia lipase-catalyzed hydrolysis of diacylated precursor. The above integrated combination of chemical asymmetric synthesis and enzyme-catalyzed kinetic resolution enabled us to prepare active DHMEQ in a large-scale. (C) 2010 Elsevier Ltd. All rights reserved.
• A Chemo-Enzymatic Expeditious Route to Racemic Dihexanoyl (2<i>R</i>*,3<i>R</i>*,4<i>R</i>*)-Dehydroxymethylepoxyquinomycin (DHMEQ), the Precursor for Lipase-Catalyzed Synthesis of the Potent Nuclear Factor-κB Inhibitor, (2<i>S</i>,3<i>S</i>,4<i>S</i>)-DHMEQ
  作者：Ryohei Kobayashi、Kengo Hanaya、Mitsuru Shoji、Kazuo Umezawa、Takeshi Sugai

  DOI：10.1248/cpb.c12-00417

  日期：——

  In order to synthesize the potent nuclear factor (NF)-κB inhibitor, (2S,3S,4S)-dehydroxymethylepoxyquinomycin (DHMEQ), in a large scale, a new route for its corresponding racemic precursor, dihexanoyl (2R*,3R*,4R*)-DHMEQ, was developed. By employing both hydroquinone and benzoquinone intermediates, the total yield, reproducibility, and synthetic steps were improved and the synthetic cost was reduced

  为了大规模合成有效的核因子（NF）-κB抑制剂（2S，3S，4S）-脱羟基甲基环氧奎霉素（DHMEQ），其相应的外消旋前体二己酰基（2R *，3R *，开发了4R *）-DHMEQ。通过同时使用氢醌和苯醌中间体，可提高总收率，重现性和合成步骤，并降低合成成本。