(3S,4S)-4-[(E,2R)-2-[tert-butyl(dimethyl)silyl]oxyhept-5-enyl]-3-hexyloxetan-2-one | 1026486-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3S,4S)-4-[(E,2R)-2-[tert-butyl(dimethyl)silyl]oxyhept-5-enyl]-3-hexyloxetan-2-one
• CAS: 1026486-59-8
• 化学式: C₂₂H₄₂O₃Si
• 分子量: 382.659
• InChiKey: RYSHSUVMYDRMQS-GEBLETALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.64
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3R,6E)-3-(tert-butyldimethylsilyloxy)oct-6-enal 、 Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanyloct-1-enoxy)silane 在 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 生成 (3S,4S)-4-[(E,2R)-2-[tert-butyl(dimethyl)silyl]oxyhept-5-enyl]-3-hexyloxetan-2-one 、
  参考文献：
  名称：

  Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

  摘要：

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.

  DOI：

  10.1021/jm800321h

文献信息

• Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase
  作者：Robyn D. Richardson、Gil Ma、Yatsandra Oyola、Manuel Zancanella、Lynn M. Knowles、Piotr Cieplak、Daniel Romo、Jeffrey W. Smith

  DOI：10.1021/jm800321h

  日期：2008.9.11

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.