3-Methyl-1-(6-methyl-chroman-8-yl)-butan-1-one | 154596-70-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-Methyl-1-(6-methyl-chroman-8-yl)-butan-1-one
• CAS: 154596-70-0
• 化学式: C₁₅H₂₀O₂
• 分子量: 232.323
• InChiKey: SXPFOYQAMNDRHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.55
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-Methyl-1-(6-methyl-chroman-8-yl)-butan-1-one 在 硼烷 、 potassium hydrogencarbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Structure-Based Design of an Inhibitor of the Zinc Peptidase Thermolysin

  摘要：

  The full cycle of design, synthesis, and enzymatic and crystallographic evaluation of a structure-based inhibitor of thermolysin is described. Using the structure of the complex of thermolysin with Cbz-Gly(P)-Leu-Leu (K-i = 9 nM; ''Gly(P)'' = NHCH2PO2-) as the starting point, we designed the macrocyclic phosphonamidate (S,S)-1 as a conformationally constrained derivative. The chroman linking unit was designed to rigidify the peptide analog while avoiding unfavorable steric interactions with the enzyme. (S,S)-1 was synthesized by a route that provided all of the stereoisomers in pure form; the acyclic control compounds 2 and 3 were also prepared. The binding affinity of (S,S)-1 (K-i = 4 nM) is enhanced by 2.3 kcal/mol in comparison to 3 (K-i = 190 nM); the other diastereomers of 1 are considerably less potent (K-i greater than or equal to 500 nM). Crystallographic analysis of the complexes between thermolysin and (S,S)-1 and (S)-2 demonstrated that the anticipated mode of binding of (S,S)-1 was fundamentally correct, while revealing some discrepancies with the original model. The structural studies also showed that the chroman moiety in the acyclic analog (S)-2 binds in a different orientation than in the macrocycle, an observation that is important for interpreting the differences in affinity between the macrocyclic inhibitor and the control compounds.

  DOI：

  10.1021/ja00087a010
• 作为产物：
  描述：

  3,4-Dihydro-6-methyl-2H-1-benzopyran 、 异戊酰氯 在 四氯化钛 作用下， 以 硝基甲烷 为溶剂， 生成 3-Methyl-1-(6-methyl-chroman-8-yl)-butan-1-one
  参考文献：
  名称：

  Structure-Based Design of an Inhibitor of the Zinc Peptidase Thermolysin

  摘要：

  The full cycle of design, synthesis, and enzymatic and crystallographic evaluation of a structure-based inhibitor of thermolysin is described. Using the structure of the complex of thermolysin with Cbz-Gly(P)-Leu-Leu (K-i = 9 nM; ''Gly(P)'' = NHCH2PO2-) as the starting point, we designed the macrocyclic phosphonamidate (S,S)-1 as a conformationally constrained derivative. The chroman linking unit was designed to rigidify the peptide analog while avoiding unfavorable steric interactions with the enzyme. (S,S)-1 was synthesized by a route that provided all of the stereoisomers in pure form; the acyclic control compounds 2 and 3 were also prepared. The binding affinity of (S,S)-1 (K-i = 4 nM) is enhanced by 2.3 kcal/mol in comparison to 3 (K-i = 190 nM); the other diastereomers of 1 are considerably less potent (K-i greater than or equal to 500 nM). Crystallographic analysis of the complexes between thermolysin and (S,S)-1 and (S)-2 demonstrated that the anticipated mode of binding of (S,S)-1 was fundamentally correct, while revealing some discrepancies with the original model. The structural studies also showed that the chroman moiety in the acyclic analog (S)-2 binds in a different orientation than in the macrocycle, an observation that is important for interpreting the differences in affinity between the macrocyclic inhibitor and the control compounds.

  DOI：

  10.1021/ja00087a010