ethyl 4-hydroxy-2-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl]-5H-1,3-thiazole-4-carboxylate | 1026007-03-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-hydroxy-2-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl]-5H-1,3-thiazole-4-carboxylate
• CAS: 1026007-03-3
• 化学式: C₁₉H₂₆N₂O₅S
• 分子量: 394.492
• InChiKey: NAIOEVIITHLPBJ-KTQQKIMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4-hydroxy-2-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl]-5H-1,3-thiazole-4-carboxylate 在 吡啶 、 三氟乙酸酐 、 三乙胺 作用下， 以 乙二醇二甲醚 为溶剂， 反应 3.25h， 以210 mg的产率得到(S)-ethyl 2-(1-(tert-butoxycarbonylamino)-2-phenylethyl)thiazole-4-carboxylate
  参考文献：
  名称：

  Synthesis, Structure–Activity Analysis, and Biological Evaluation of Sanguinamide B Analogues

  摘要：

  We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only L- and D-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.

  DOI：

  10.1021/jo3017499
• 作为产物：
  描述：

  N-叔丁氧羰基-L-苯丙氨酸甲酯 在 劳森试剂 、 ammonium hydroxide 、 potassium hydrogencarbonate 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 0.25h， 生成 ethyl 4-hydroxy-2-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl]-5H-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  Synthesis, Structure–Activity Analysis, and Biological Evaluation of Sanguinamide B Analogues

  摘要：

  We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only L- and D-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.

  DOI：

  10.1021/jo3017499

文献信息

• Synthesis, Structure–Activity Analysis, and Biological Evaluation of Sanguinamide B Analogues
  作者：Hendra Wahyudi、Worawan Tantisantisom、Xuechao Liu、Deborah M. Ramsey、Erinprit K. Singh、Shelli R. McAlpine

  DOI：10.1021/jo3017499

  日期：2012.12.7

  We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only L- and D-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.