(1R,4R,5S)-4-(2-chloroethyl)-5-methyl-1-((S)-4,4,4-trifluoro-1-hydroxybutyl)-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione | 1367878-76-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1R,4R,5S)-4-(2-chloroethyl)-5-methyl-1-((S)-4,4,4-trifluoro-1-hydroxybutyl)-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione
• 英文别名: (1R,4R,5S)-4-(2-chloroethyl)-5-methyl-1-[(1S)-4,4,4-trifluoro-1-hydroxybutyl]-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione
• CAS: 1367878-76-9
• 化学式: C₁₂H₁₅ClF₃NO₄
• 分子量: 329.704
• InChiKey: KKFSBSAGKRNVRX-RQBXAUFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (3R,3aS,7aR)-3-Benzyloxymethyl-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester 在 吡啶 、 potassium fluoride 、 ammonium cerium (IV) nitrate 、 20 % Pd(OH)2/C 、 水 、 氢气 、 双氧水 、 叔丁基锂 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 lithium hydroxide 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 乙腈 、 正戊烷 为溶剂， 反应 40.0h， 生成 (1R,4R,5S)-4-(2-chloroethyl)-5-methyl-1-((S)-4,4,4-trifluoro-1-hydroxybutyl)-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione
  参考文献：
  名称：

  Coupling of sterically hindered aldehyde with fluorinated synthons: Stereoselective synthesis of fluorinated analogues of salinosporamide A

  摘要：

  Salinosporamide A is an irreversible inhibitor of the beta-subunits of the 20S proteasome. Its C-5 cyclohexenyl moiety is the key to its affinity and potency as an anticancer agent. Here we describe the synthesis of C-5 difluoromethylated and trifluoromethylated analogues of salinosporamide A and their biological evaluation as proteasome inhibitors against purified yeast 20S proteasome. The synthetic strategy featured the stereoselective coupling reaction of sterically hindered aldehyde 3 with fluorinated organolithium reagents. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2012.01.003

文献信息

• Coupling of sterically hindered aldehyde with fluorinated synthons: Stereoselective synthesis of fluorinated analogues of salinosporamide A
  作者：Zeng-Hao Chen、Bing-Lin Wang、Andrew J. Kale、Bradley S. Moore、Ruo-Wen Wang、Feng-Ling Qing

  DOI：10.1016/j.jfluchem.2012.01.003

  日期：2012.4

  Salinosporamide A is an irreversible inhibitor of the beta-subunits of the 20S proteasome. Its C-5 cyclohexenyl moiety is the key to its affinity and potency as an anticancer agent. Here we describe the synthesis of C-5 difluoromethylated and trifluoromethylated analogues of salinosporamide A and their biological evaluation as proteasome inhibitors against purified yeast 20S proteasome. The synthetic strategy featured the stereoselective coupling reaction of sterically hindered aldehyde 3 with fluorinated organolithium reagents. (C) 2012 Elsevier B.V. All rights reserved.