4-[(2R)-2-[tert-butyl(dimethyl)silyl]oxytridecyl]-3-hexyloxetan-2-one | 1197399-35-1

• 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: 4-[(2R)-2-[tert-butyl(dimethyl)silyl]oxytridecyl]-3-hexyloxetan-2-one
• CAS: 1197399-35-1
• 化学式: C₂₈H₅₆O₃Si
• 分子量: 468.836
• InChiKey: BKEBYVHFOIJQDK-JDSVYEKJSA-N

物化性质

• 沸点：
  507.6±23.0 °C(Predicted)
• 密度：
  0.896±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  32
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(2R)-2-[tert-butyl(dimethyl)silyl]oxytridecyl]-3-hexyloxetan-2-one 在 偶氮二甲酸二异丙酯 、 氢氟酸 、 三苯基膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 7.0h， 生成 奥利司他
  参考文献：
  名称：

  Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative:  Inhibitors of Fatty Acid Synthase

  摘要：

  Concise syntheses of orlistat ( Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol-lactonization (TMAL) process as a key step. This process allows facile modification of the alpha-side chain. Versatile strategies for modifying the delta-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling.

  DOI：

  10.1021/ol061651o
• 作为产物：
  描述：

  3-氧代十四酸乙酯 在 二异丁基氢化铝 、 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 生成 4-[(2R)-2-[tert-butyl(dimethyl)silyl]oxytridecyl]-3-hexyloxetan-2-one
  参考文献：
  名称：

  Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative:  Inhibitors of Fatty Acid Synthase

  摘要：

  Concise syntheses of orlistat ( Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol-lactonization (TMAL) process as a key step. This process allows facile modification of the alpha-side chain. Versatile strategies for modifying the delta-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling.

  DOI：

  10.1021/ol061651o

文献信息

• BETA-LACTONE COMPOUNDS
  申请人：Smith Jeffrey W.

  公开号：US20090124681A1

  公开（公告）日：2009-05-14

  The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R 1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

  本发明提供具有一般结构A的化合物，或其药学上可接受的衍生物：其中R是烷基基团，R1包括至少一种从烷基、烯基、芳基、杂环、羟基、酯、酰胺、醛基和卤素组成的基团。
• Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities
  作者：Peng-Yu Yang、Kai Liu、Mun Hong Ngai、Martin J. Lear、Markus R. Wenk、Shao Q. Yao

  DOI：10.1021/ja907716f

  日期：2010.1.20

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.
• β-Lactam congeners of orlistat as inhibitors of fatty acid synthase
  作者：Wei Zhang、Robyn D. Richardson、Supakarn Chamni、Jeffrey W. Smith、Daniel Romo

  DOI：10.1016/j.bmcl.2008.02.043

  日期：2008.4

  beta-Lactam derivatives of orlistat were prepared and their inhibitory activities toward the thioesterase domain of fatty acid synthase (FAS-TE) were evaluated using a recombinant form of the enzyme. While in general these derivatives showed lower potency compared to beta-lactones, a reasonably potent, lead compound (-)-9 (IC50 = 8.6 mu M) was discovered that suggests that this class of compounds should be evaluated further. (C) 2008 Published by Elsevier Ltd.
• THE PREPARATION METHOD OF (3S,4S)-3-HEXYL-4-((R)-2-HYDROXYTRIDECYL)-OXETAN-2-ONE AND THE PRODUCT OF THAT METHOD
  申请人：Chongqing Zhien Pharmaceutical Co., Ltd.

  公开号：EP2280007B1

  公开（公告）日：2015-04-29
• Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative:  Inhibitors of Fatty Acid Synthase
  作者：Gil Ma、Manuel Zancanella、Yatsandra Oyola、Robyn D. Richardson、Jeffrey W. Smith、Daniel Romo

  DOI：10.1021/ol061651o

  日期：2006.9.1

  Concise syntheses of orlistat ( Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol-lactonization (TMAL) process as a key step. This process allows facile modification of the alpha-side chain. Versatile strategies for modifying the delta-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling.