[(3S)-5-oxooxolan-3-yl] but-3-enoate | 1351762-74-7

• 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: [(3S)-5-oxooxolan-3-yl] but-3-enoate
• CAS: 1351762-74-7
• 化学式: C₈H₁₀O₄
• 分子量: 170.165
• InChiKey: FDZXJNPVCFAPCT-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(3S)-5-oxooxolan-3-yl] but-3-enoate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 4-二甲氨基吡啶 、 N-氯代丁二酰亚胺 、 甲酸 、 苯基氯化硒 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 52.08h， 生成
  参考文献：
  名称：

  Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway

  摘要：

  The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-L-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keapl. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.

  DOI：

  10.1021/acs.jnatprod.7b00734
• 作为产物：
  描述：

  乙烯基乙酸 、 (S)-(-)-β-羟基-γ-丁内酯 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.08h， 以52%的产率得到[(3S)-5-oxooxolan-3-yl] but-3-enoate
  参考文献：
  名称：

  Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway

  摘要：

  The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-L-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keapl. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.

  DOI：

  10.1021/acs.jnatprod.7b00734

文献信息

• Honaucins A−C, Potent Inhibitors of Inflammation and Bacterial Quorum Sensing: Synthetic Derivatives and Structure-Activity Relationships
  作者：Hyukjae Choi、Samantha J. Mascuch、Francisco A. Villa、Tara Byrum、Margaret E. Teasdale、Jennifer E. Smith、Linda B. Preskitt、David C. Rowley、Lena Gerwick、William H. Gerwick

  DOI：10.1016/j.chembiol.2012.03.014

  日期：2012.5

  Honaucins A-C were isolated from the cyanobacterium Leptolyngbya crossbyana which was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3-hydroxy-gamma-butyrolactone and 4-chlorocrotonic acid, which are connected via an ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition of both bioluminescence, a quorum-sensing-dependent phenotype, in Vibrio harveyi BB120 and lipopolysaccharide-stimulated nitric oxide production in the murine macrophage cell line RAW264.7. The decrease in nitric oxide production was accompanied by a decrease in the transcripts of several proinflammatory cytokines, most dramatically interleukin-1 beta. Synthesis of honaucin A, as well as a number of analogs, and subsequent evaluation in anti-inflammation and quorum-sensing inhibition bioassays revealed the essential structural features for activity in this chemical class and provided analogs with greater potency in both assays.
• ANTI-INFLAMMATORY AND QUORUM SENSING INHIBITION COMPOUNDS AND METHODS OF MAKING AND USING THEM
  申请人：Gerwick William

  公开号：US20140147481A1

  公开（公告）日：2014-05-29

  The invention provides novel compositions based on a structure designated as “Honaucin A”, including Honaucin A variants and analogs, and pharmaceutical compositions, liposomes and nanoparticles comprising them, and methods of making and using them. In one embodiment these Honaucin A compounds, and variants and analogs thereof are used to ameliorate (including to treat or prevent) inflammation. In one embodiment, these Honaucin A compounds, and variants and analogs thereof are used to ameliorate (including to treat or prevent) inflammation. In one embodiment, these Honaucin A compounds, and variants and analogs thereof are used as bacterial quorumsensing inhibitors. Accordingly, in alternative embodiments the compositions of the invention are used as anti-bacterial agents.
• US9073884B2
  申请人：——

  公开号：US9073884B2

  公开（公告）日：2015-07-07
• Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway
  作者：Samantha J. Mascuch、Paul D. Boudreau、Tristan M. Carland、N. Tessa Pierce、Joshua Olson、Mary E. Hensler、Hyukjae Choi、Joseph Campanale、Amro Hamdoun、Victor Nizet、William H. Gerwick、Teresa Gaasterland、Lena Gerwick

  DOI：10.1021/acs.jnatprod.7b00734

  日期：2018.3.23

  The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-L-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keapl. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.