(S)-3-(tert-butyldimethylsilyloxy)tetradecanal | 108052-01-3

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (S)-3-(tert-butyldimethylsilyloxy)tetradecanal
• 英文别名: (S)-3-tetradecanal；(S)-3-(t-butyldimethylsiloxy)tetradecanal；(3S)-3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]tetradecanal；(3S)-3-[tert-butyl(dimethyl)silyl]oxytetradecanal
• CAS: 108052-01-3
• 化学式: C₂₀H₄₂O₂Si
• 分子量: 342.638
• InChiKey: PIQPQYDHYCTWIZ-IBGZPJMESA-N

物化性质

• 沸点：
  383.5±25.0 °C(Predicted)
• 密度：
  0.859±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.89
• 重原子数：
  23
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-3-(tert-butyldimethylsilyloxy)tetradecanal 、 (E)-2-(1-(tert-butyldimethylsilyloxy)oct-1-enylthio)pyridine 在 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以60%的产率得到(3RS,4RS)-4-[(2S)-2-{[tert-butyl(dimethyl)silyl]-oxy}tridecyl]-3-hexyloxetan-2-one
  参考文献：
  名称：

  β-Lactam congeners of orlistat as inhibitors of fatty acid synthase

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2008.02.043
• 作为产物：
  描述：

  methyl (S)-3-(tert-butyldimethylsilyloxy)tetradecanoate 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 反应 3.5h， 生成 (S)-3-(tert-butyldimethylsilyloxy)tetradecanal
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARATION OF OXETAN-2-ONES
  [FR] PROCEDE DE PREPARATION D'OXETAN-2-ONES

  摘要：

  公开号：

  WO2005005403A3

文献信息

• Oxetanones and process for their production
  申请人：Hoffmann-La Roche Inc.

  公开号：US04983746A1

  公开（公告）日：1991-01-08

  The invention is directed to a process for the manufacture of pancreatic lipase-inhibiting oxetanone ethyl esters of the formula ##STR1## wherein X is undecyl or 2Z,5Z-undecadienyl; C.sub.6 is n-hexyl; Y is isobutyl and Z is formyl or Y is carbamoylmethyl and Z is acetyl; which process comprises esterifying the corresponding oxetanone ethanols, or hydrogenating the 3-undecenyl group in corresponding oxetanone ethyl ester starting materials to the undecyl group X, or N-formylating or N-acetylating corresponding primary amines.

  该发明涉及一种制备胰脂酶抑制剂氧杂环戊酮乙酯的工艺，其化学式为##STR1##其中X为十一烷基或2Z,5Z-十一烯基；C.sub.6为正己基；Y为异丁基，Z为甲酰基或Y为氨甲基，Z为乙酰基；该工艺包括酯化相应的氧杂环戊酮乙醇，或在相应的氧杂环戊酮乙酯起始原料中氢化3-十一烯基团至十一烷基X，或对应的主要胺基进行N-甲酰化或N-乙酰化。
• Chemical Modification and Organelle-Specific Localization of Orlistat-Like Natural-Product-Based Probes
  作者：Peng-Yu Yang、Kai Liu、Chongjing Zhang、Grace Y. J. Chen、Yuan Shen、Mun Hong Ngai、Martin J. Lear、Shao Q. Yao

  DOI：10.1002/asia.201100306

  日期：2011.10.4

  Orlistat, also known as tetrahydrolipstatin (THL), is an FDA‐approved anti‐obesity drug with potential anti‐cancer activity. Previously, we developed a chemical proteomic approach, based on the Orlistat‐like probe (1a) for large‐scale identification of unknown cellular targets of Orlistat in human hepatocytes. In this article, we report the chemical synthesis and biological evaluation of an expanded

  奥利司他（Orlistat），也称为四氢脂质他汀（THL），是FDA批准的抗肥胖药，具有潜在的抗癌活性。以前，我们基于类Orlistat探针（1a）用于大规模鉴定人肝细胞中奥利司他的未知细胞靶标。在本文中，我们报告了一系列扩展的Orlistat样化合物的化学合成和生物学评估，目的是进一步剖析和操纵Orlistat的潜在细胞靶标。为此，我们对活HepG2细胞中的这些化合物进行了基于蛋白质组的活动分析和大规模下拉/ LCMS分析，并成功地确定了Orlistat及其结构类似物的许多推定细胞靶标。通过定性评估针对17种奥利司他类似物的潜在蛋白质命中的光谱计数，我们获得了这些探针的共同和独特靶标。我们的结果表明，奥利司他的微妙结构修饰导致该药物的细胞效能和靶标分布均发生了显着变化。为了进一步提高Orlistat的细胞活性，我们成功地将成熟的AGT / SNAP标签技术应用于我们的细胞渗透性含苄基鸟嘌
• 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.
• [EN] PROCESS FOR PREPARATION OF OXETAN-2-ONES<br/>[FR] PROCEDE DE PREPARATION D'OXETAN-2-ONES
  申请人：RANBAXY LAB LTD

  公开号：WO2005005403A3

  公开（公告）日：2005-04-07
• 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.