4-oxo-2-hexenal

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-oxo-2-hexenal
• 英文别名: 4-oxohex-2-enal
• 化学式: C₆H₈O₂
• 分子量: 112.128
• InChiKey: GVKYFODEMNCLGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-oxo-2-hexenal 、 2'-脱氧胞苷盐酸盐 以 乙醇 为溶剂， 反应 120.0h， 以32%的产率得到8-(2-oxobutyl)-3,N4-etheno-dC
  参考文献：
  名称：

  DNA Modifications by the ω-3 Lipid Peroxidation-Derived Mutagen 4-Oxo-2-hexenal in Vitro and Their Analysis in Mouse and Human DNA

  摘要：

  4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4-OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental lipid peroxides.

  DOI：

  10.1021/tx9003819
• 作为产物：
  描述：

  2-乙基呋喃 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 水 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 以300 mg的产率得到4-oxo-2-hexenal
  参考文献：
  名称：

  Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity

  摘要：

  In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5 alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3 beta-hydroxysteroids, showing K-m of 1.3-9.1 mu M and k(cat) of 1.1-7.6 min(-1). The stereospecific reduction was also observed in the metabolism of 5 alpha- and 5 beta-dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3 beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2012.07.012

文献信息

• N-Heterocyclic Carbene and Brønsted Acid Cooperative Catalysis: Asymmetric Synthesis of <i>trans</i>-γ-Lactams
  作者：Xiaodan Zhao、Daniel A. DiRocco、Tomislav Rovis

  DOI：10.1021/ja205714g

  日期：2011.8.17

  An efficient enantioselective approach to form trans-γ-lactams in up to 99% yield, 93% ee, and >20/1 dr using unactivated imines has been developed. The cyclohexyl-substituted azolium and the weak base sodium o-chlorobenzoate are most suitable for this transformation. Notably, the process involves cooperative catalysis by an N-heterocyclic carbene and a Brønsted acid.

  已经开发出一种使用未活化亚胺以高达 99% 的产率、93% 的 ee 和 >20/1 dr 的高效对映选择性方法形成反式-γ-内酰胺。环己基取代的唑鎓和弱碱邻氯苯甲酸钠最适合这种转化。值得注意的是，该过程涉及 N-杂环卡宾和布朗斯台德酸的协同催化。
• Diastereoselective Total Synthesis of (±)-Schindilactone A, Part 1: Construction of the ABC and FGH Ring Systems and Initial Attempts to Construct the CDEF Ring System
  作者：Tian-Wen Sun、Wei-Wu Ren、Qing Xiao、Ye-Feng Tang、Yan-Dong Zhang、Yong Li、Fan-Ke Meng、Yi-Fan Liu、Ming-Zhe Zhao、Ling-Min Xu、Jia-Hua Chen、Zhen Yang

  DOI：10.1002/asia.201200363

  日期：2012.10

  strategies for the diastereoselective total synthesis of schindilactone A (1) are presented and methods for the synthesis of the ABC, FGH, and CDEF moieties are explored. We have established a method for the synthesis of the ABC moiety, which included both a Diels–Alder reaction and a ring‐closing metathesis as the key steps. We have also developed a method for the synthesis of the FGH moiety, which involved

  schindilactonetone A（1的非对映选择性全合成的第一代合成策略），并提出了合成ABC，FGH和CDEF部分的方法。我们已经建立了合成ABC部分的方法，其中包括Diels-Alder反应和闭环易位作为关键步骤。我们还开发了一种合成FGH部分的方法，该方法涉及使用Pauson-Khand反应和羰基环化反应作为关键步骤。此外，我们通过使用[3,3]重排作为关键步骤，实现了中央7-8双环系统的构建。然而，不幸的是，当将该重排反应应用于更高级的CDEF部分的构建时，预期的环化反应并未发生，并且需要替代的合成策略来开发该中心核。
• Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity
  作者：Satoshi Endo、Toshiyuki Matsunaga、Sho Kumada、Airi Fujimoto、Satoshi Ohno、Ossama El-Kabbani、Dawei Hu、Naoki Toyooka、Jun’ichi Mano、Kazuo Tajima、Akira Hara

  DOI：10.1016/j.abb.2012.07.012

  日期：2012.11

  In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5 alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3 beta-hydroxysteroids, showing K-m of 1.3-9.1 mu M and k(cat) of 1.1-7.6 min(-1). The stereospecific reduction was also observed in the metabolism of 5 alpha- and 5 beta-dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3 beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate. (C) 2012 Elsevier Inc. All rights reserved.
• DNA Modifications by the ω-3 Lipid Peroxidation-Derived Mutagen 4-Oxo-2-hexenal in Vitro and Their Analysis in Mouse and Human DNA
  作者：Kazuaki Kawai、Pei-Hsin Chou、Tomonari Matsuda、Masaaki Inoue、Kaisa Aaltonen、Kirsti Savela、Yoshikazu Takahashi、Hikaru Nakamura、Tomoyuki Kimura、Takumi Watanabe、Ryuichi Sawa、Kazuyuki Dobashi、Yun-Shan Li、Hiroshi Kasai

  DOI：10.1021/tx9003819

  日期：2010.3.15

  4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4-OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental lipid peroxides.