2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide

• 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: 2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide
• 英文别名: dehydroxymethylepoxyquinomicin；rac-(2S,3S,4S)-dehydroxymethylepoxyquinomycin；(+)-Dhmeq；2-hydroxy-N-[(1R,2R,6R)-2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]benzamide
• 化学式: C₁₃H₁₁NO₅
• 分子量: 261.234
• InChiKey: IUOMATKBBPCLFR-GRYCIOLGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide 在 氢氟酸 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (-)-2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide
  参考文献：
  名称：

  Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C

  摘要：

  In order to develop new inhibitors of NF-kappa B activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappa B in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00114-1
• 作为产物：
  描述：

  邻乙酰水杨酰氯 在 吡啶 、 sodium hydroxide 、 碘苯二乙酸 、 双氧水 、 三乙酰氧基硼氢化钠 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 5.17h， 生成 2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide
  参考文献：
  名称：

  Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C

  摘要：

  In order to develop new inhibitors of NF-kappa B activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappa B in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00114-1

文献信息

• Chemoenzymatic synthesis of (2R,3R,4R)-dehydroxymethylepoxyquinomicin (DHMEQ), a new activator of antioxidant transcription factor Nrf2
  作者：Yukihiro Niitsu、Masatoshi Hakamata、Yuko Goto、Toshinori Higashi、Mitsuru Shoji、Takeshi Sugai、Kazuo Umezawa

  DOI：10.1039/c1ob05205e

  日期：——

  >500) to give (1S,2S,3S)-2a in an enantiomerically pure state. Several chemical steps of transformation from the enzyme reaction product gave (2R,3R,4R)-DHMEQ (1a) without any loss of stereochemical purity. Moreover, we newly found that (2R,3R,4R)-DHMEQ activated Nrf2, which is a transcription factor that induces the expression of multiple antioxidant enzymes. It activated Nrf2 in a promoter reporter assay

  Dehydroxymethylepoxyquinomicnomicin（DHMEQ，1a）是NF-κB的特异有效抑制剂，目前正被开发为抗炎和抗癌药。尽管以前通过脂肪酶催化的对映选择性拆分只能从外消旋物中获得（2S，3S，4S）形式，但在本研究中，通过以下方法建立了生产（2R，3R，4R）形式的新途径使用化学酶学方法。（1R *，2R *，3R *）-2,3-环氧-5-N-[（2-羟基苯甲酰基）氨基] -4,4-二甲氧基环己基-5-烯-1-醇（2a）在两者上均被己酰化仲和酚羟基，并进行伯克霍尔德酒原脂酶的水解。反应以高度对映选择性的方式进行（E> 500），得到对映体纯态的（1S，2S，3S）-2a。从酶反应产物转化的几个化学步骤得到了（2R，3R，4R）-DHMEQ（1a），而没有任何立体化学纯度的损失。此外，我们新发现（2R，3R，4R）-DHMEQ激活了Nrf2，Nrf2是诱导多种抗氧
• 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。
• Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor
  作者：Yoshikazu Suzuki、Chie Sugiyama、Osamu Ohno、Kazuo Umezawa

  DOI：10.1016/j.tet.2004.01.103

  日期：2004.8

  NF-kappaB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-kappaB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-kappaB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells. (C) 2004 Elsevier Ltd. All rights reserved.
• Macrophage activation inhibitor
  申请人：Umezawa Kazuo

  公开号：US20070142465A1

  公开（公告）日：2007-06-21

  A compound represented by the following general formula (1): wherein R 1 represents a hydrogen atom or a C2 to C4 alkanoyl group and R 2 represents a group represented by the following formula (A), (B), (C), (D), (E), (F), or (G): wherein R 3 represents a C1 to C4 alkyl group can inhibit macrophage activation. Accordingly, a macrophage activation inhibitor containing a compound represented by the general formula (1) or its pharmacologically acceptable salt as an active ingredient is useful as an agent for preventing, improving, or treating a disease resulting from infection with pathogens such as a bacterium and a virus.
• Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C
  作者：Naoki Matsumoto、Akiko Ariga、Sakino To-e、Hikaru Nakamura、Naoki Agata、Shin-ichi Hirano、Jun-ichiro Inoue、Kazuo Umezawa

  DOI：10.1016/s0960-894x(00)00114-1

  日期：2000.5

  In order to develop new inhibitors of NF-kappa B activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappa B in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice. (C) 2000 Elsevier Science Ltd. All rights reserved.