(2R,3S)-3-fluoro-2-methylhexadecanoic acid | 943135-83-9

• 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: (2R,3S)-3-fluoro-2-methylhexadecanoic acid
• CAS: 943135-83-9
• 化学式: C₁₇H₃₃FO₂
• 分子量: 288.446
• InChiKey: YKMCRMBPQOPFSC-HOTGVXAUSA-N

物化性质

• 沸点：
  390.4±12.0 °C(Predicted)
• 密度：
  0.930±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  20
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  coenzyme A trilithium salt 、 (2R,3S)-3-fluoro-2-methylhexadecanoic acid 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以26%的产率得到
  参考文献：
  名称：

  Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors

  摘要：

  The enzyme alpha-methylacyl-CoA racemase (AMACR) is overexpressed in prostate, colon, and other cancers and has been partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene. Analogs of the natural substrate branched chain alpha-methylacyl coenzyme A esters, possessing one or more beta-fluorine atoms, have been synthesized using Wittig, conjugate addition, and asymmetric aldol reactions and found to be reversible competitive inhibitors. Each diastereomer of the previously reported inhibitor ibuprofenoyl-CoA was also tested. The compounds had K-i values of 0.9-20 mu M and are the most potent inhibitors yet known. The presence of beta-fluorine on the alpha-methyl group or the acyl chain results in a significant lowering of the K-i value compared with nonfluorinated analogs, and this is attributed to a lowering of the pK(a) of the alpha-proton, facilitating enolization and binding. Several of the CoA ester inhibitors were formed by incubating the free carboxylic acid precursors with cell free extracts and CoA. alpha-Trifluoromethyltetradecanoic acid, the precursor to the most potent inhibitor, was shown to inhibit growth of cancer cell lines PC3, CWR22 Rv1, and Du145 in a dose-dependent manner and could be related to the expression level of AMACR.

  DOI：

  10.1021/jm0702377
• 作为产物：
  描述：

  N-(2S,3R,4'S)-(3-hydroxy-2-methylhexadecanoyl)-4'-isopropyl-3-propionyloxazolidin-2'-one 在 lithium hydroxide 、 双氧水 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2R,3S)-3-fluoro-2-methylhexadecanoic acid
  参考文献：
  名称：

  Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors

  摘要：

  The enzyme alpha-methylacyl-CoA racemase (AMACR) is overexpressed in prostate, colon, and other cancers and has been partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene. Analogs of the natural substrate branched chain alpha-methylacyl coenzyme A esters, possessing one or more beta-fluorine atoms, have been synthesized using Wittig, conjugate addition, and asymmetric aldol reactions and found to be reversible competitive inhibitors. Each diastereomer of the previously reported inhibitor ibuprofenoyl-CoA was also tested. The compounds had K-i values of 0.9-20 mu M and are the most potent inhibitors yet known. The presence of beta-fluorine on the alpha-methyl group or the acyl chain results in a significant lowering of the K-i value compared with nonfluorinated analogs, and this is attributed to a lowering of the pK(a) of the alpha-proton, facilitating enolization and binding. Several of the CoA ester inhibitors were formed by incubating the free carboxylic acid precursors with cell free extracts and CoA. alpha-Trifluoromethyltetradecanoic acid, the precursor to the most potent inhibitor, was shown to inhibit growth of cancer cell lines PC3, CWR22 Rv1, and Du145 in a dose-dependent manner and could be related to the expression level of AMACR.

  DOI：

  10.1021/jm0702377