6,8-dibromo-3-(chloromethyl)coumarin | 515160-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6,8-dibromo-3-(chloromethyl)coumarin
• 英文别名: 3-chloromethyl-6,8-dibromocoumarin；6,8-Dibromo-3-(chloromethyl)chromen-2-one
• CAS: 515160-02-8
• 化学式: C₁₀H₅Br₂ClO₂
• 分子量: 352.41
• InChiKey: PHHMDNFXOKYBOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-(2',3',5'-tri-O-acetyl-β-D-ribofuranos-1'-yl)purine-8-thione 、 6,8-dibromo-3-(chloromethyl)coumarin 在 氨 作用下， 以 水 、 乙腈 为溶剂， 反应 3.5h， 以77%的产率得到8-(6',8'-dibromocoumarin-3'-yl)methylthio-9-(2'',3'',5''-tri-O-acetyl-β-D-ribofuranos-1''-yl)purine
  参考文献：
  名称：

  Coumarin−Purine Ribofuranoside Conjugates as New Agents against Hepatitis C Virus

  摘要：

  About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-a and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(beta-D-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substitucnts. A -SCH2- unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2'-, 3'-, and 5'-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure activity relationship was established. Three conjugates in the family of 8-(coumarin-3'-yl)methylthio-9-(beta-D-ribofuranos-1 ''-yl)purine possessed an appealing ability to inhibit HCV replication with EC50 between 5.5 and 6.6 mu M and EC90 of similar to 20 mu M. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.

  DOI：

  10.1021/jm101337v
• 作为产物：
  描述：

  2-苄氧基-3,5-二溴苯甲醛 在 三乙烯二胺 、 盐酸 作用下， 以 氯仿 、 乙酸酐 、 溶剂黄146 为溶剂， 生成 6,8-dibromo-3-(chloromethyl)coumarin
  参考文献：
  名称：

  A Convenient and Improved Baylis-Hillman Synthesis of 3-Substituted 2H-1-benzopyran-2-ones

  摘要：

  研究表明，使用 O-苄基水杨醛前体对巴利斯-希尔曼（Baylis-Hillman）产物进行卤酸催化脱保护和环化，可以化学选择性地获得 3-（卤甲基）香豆素（3-卤甲基-2H-1-苯并吡喃-2-酮），而且收率很高。

  DOI：

  10.1055/s-2002-35984

文献信息

• Does the DABCO-catalysed reaction of 2-hydroxybenzaldehydes with methyl acrylate follow a Baylis–Hillman pathway?
  作者：Perry T. Kaye、Musiliyu A. Musa、Xolani W. Nocanda、Ross S. Robinson

  DOI：10.1039/b300360d

  日期：2003.3.27

  Evidence is presented which supports the intermediacy of dipolar Baylis-Hillman-type adducts in the synthesis of coumarin and chromene derivatives from the reaction of 2-hydroxybenzaldehydes with methyl acrylate in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO).

  提出的证据支持在2-羟基苯甲醛与丙烯酸甲酯在1，4-二氮杂双环[2.2.2]辛烷（DABCO）存在下合成香豆素和色烯衍生物中偶极Baylis-Hillman型加合物的中间体。 ）。
• Regioselectivity of Reactions of Nitrogen and Carbon Nucleophiles with Coumarin Derivatives
  作者：Perry T. Kaye、Musiliyu A. Musa

  DOI：10.1081/scc-200030643

  日期：2004.1.1

  Abstract Reaction of various 3‐substituted coumarins with nitrogen and carbon nucleophiles appears to involve, in all cases examined, exclusive, direct substitution at the exocyclic C‐1′ electrophilic center.

  摘要 各种 3-取代香豆素与氮和碳亲核试剂的反应似乎涉及在所有检查的情况下，在环外 C-1' 亲电中心的排他性直接取代。
• Efficient and Chemoselective Access to 3-(Chloromethyl)coumarins via Direct Cyclisation of Unprotected Baylis-Hillman Adducts
  作者：Perry T. Kaye、Musiliyu A. Musa、Xolani W. Nocanda

  DOI：10.1055/s-2003-37655

  日期：——

  Reaction of substituted 2-hydroxybenzaldehydes with t-butyl acrylate in the presence of DABCO has been shown to afford isolable Baylis-Hillman adducts, acid-catalysed cyclisation of which affords the corresponding 3-(chloromethyl)coumarins directly and in high yield.

  在DABCO存在下，取代的2-羟基苯甲醛与丙烯酸叔丁酯的反应，已证明可产生可分离的Baylis-Hillman加合物，其酸催化环化反应可直接且高收率地产生相应的3-(氯甲基)香豆素。