(S)-4,4,4-trifluoro-2-methylbutan-1-ol | 156040-09-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-4,4,4-trifluoro-2-methylbutan-1-ol
• 英文别名: (2S)-4,4,4-trifluoro-2-methylbutan-1-ol
• CAS: 156040-09-4
• 化学式: C₅H₉F₃O
• 分子量: 142.121
• InChiKey: SSXCXTKPQAFQAP-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-4,4,4-trifluoro-2-methylbutan-1-ol 在 吡啶 、 4-二甲氨基吡啶 、 sodium iodide 作用下， 以 二甲基亚砜 为溶剂， 反应 2.5h， 生成 (R)-5,5,5-trifluoro-3-methylpentanenitrile
  参考文献：
  名称：

  Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

  摘要：

  开发了一种立体选择性合成(2S,3S)-5,5,5-三氟异亮氨酸(L-5-F3Ile)和(2R,3S)-5,5,5-三氟-异亮氨酸(D-5-F3-allo-Ile)的实用路线。检查了L-5-F3Ile的亲水性，并通过固相肽合成将其并入模型肽中，以确定其α-螺旋倾向性。与Ile相比，5-F3Ile的α-螺旋倾向性显著降低，但与4'-F3Ile相比则令人惊讶地高。

  DOI：

  10.3762/bjoc.9.236
• 作为产物：
  描述：

  (S)-4-benzyl-3-[(S)-4,4,4-trifluoro-2-methylbutanoyl]oxazolidin-2-one 在 锂硼氢 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 生成 (S)-4,4,4-trifluoro-2-methylbutan-1-ol
  参考文献：
  名称：

  Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

  摘要：

  开发了一种立体选择性合成(2S,3S)-5,5,5-三氟异亮氨酸(L-5-F3Ile)和(2R,3S)-5,5,5-三氟-异亮氨酸(D-5-F3-allo-Ile)的实用路线。检查了L-5-F3Ile的亲水性，并通过固相肽合成将其并入模型肽中，以确定其α-螺旋倾向性。与Ile相比，5-F3Ile的α-螺旋倾向性显著降低，但与4'-F3Ile相比则令人惊讶地高。

  DOI：

  10.3762/bjoc.9.236

文献信息

• Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4
  作者：Robert T. Jacobs、Peter R. Bernstein、Laura A. Cronk、Edward P. Vacek、Lisa F. Newcomb、David Aharony、Carl K. Buckner、Edward J. Kusner

  DOI：10.1021/jm00035a008

  日期：1994.4

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.