(4S)-4-<(2R)-Acetoxy-2-phenylacetoxy>pentadec-1-ene | 152906-16-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (4S)-4-<(2R)-Acetoxy-2-phenylacetoxy>pentadec-1-ene
• 英文别名: (4S)-4-[(2R)-acetoxy-2-phenylacetoxy]pentadec-1-ene；[(4S)-pentadec-1-en-4-yl] (2R)-2-acetyloxy-2-phenylacetate
• CAS: 152906-16-6
• 化学式: C₂₅H₃₈O₄
• 分子量: 402.574
• InChiKey: PFHQGJZBISBLGP-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  29
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-4-<(2R)-Acetoxy-2-phenylacetoxy>pentadec-1-ene 在 四氯化钛 氢氧化钾 、 二甲基硫 、 potassium hydride 、 potassium carbonate 、 臭氧 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 13.17h， 生成 Phenyl (3S,5R)-5-(benzyloxy)-3-hydroxydecanethioate
  参考文献：
  名称：

  Total synthesis of (-)-tetrahydrolipstatin

  摘要：

  The total synthesis of (-)-tetrahydrolipstatin utilizing two approaches is described. In the first, L-malic acid was used as a chiral template to obtain enantiomerically pure (R)-3-(benzyloxy)-tetradecanal (11) which was chain-extended using 1-(trimethylsilyl)-2-nonene and a Lewis acid. This advanced intermediate was further elaborated to the target compound in good overall yield. The second approach utilized lauraldehyde as a starting material and capitalizes on an asymmetric allylboronation (91 % ee). The product could be obtained enantiomerically pure by conversion to the (R)-acetoxymandelate ester and hydrolysis. Oxidative cleavage of the terminal double bond led to 11 which was further extended using 1,3- and 1,2-asymmetric induction based on existing neighboring chirality. The synthesis of tetrahydrolipstatin using the second approach comprises seven steps from 11 and proceeds in 38 % overall yield.

  DOI：

  10.1021/jo00079a022
• 作为产物：
  描述：

  十二醛 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (4S)-4-<(2R)-Acetoxy-2-phenylacetoxy>pentadec-1-ene
  参考文献：
  名称：

  Total synthesis of (-)-tetrahydrolipstatin

  摘要：

  The total synthesis of (-)-tetrahydrolipstatin utilizing two approaches is described. In the first, L-malic acid was used as a chiral template to obtain enantiomerically pure (R)-3-(benzyloxy)-tetradecanal (11) which was chain-extended using 1-(trimethylsilyl)-2-nonene and a Lewis acid. This advanced intermediate was further elaborated to the target compound in good overall yield. The second approach utilized lauraldehyde as a starting material and capitalizes on an asymmetric allylboronation (91 % ee). The product could be obtained enantiomerically pure by conversion to the (R)-acetoxymandelate ester and hydrolysis. Oxidative cleavage of the terminal double bond led to 11 which was further extended using 1,3- and 1,2-asymmetric induction based on existing neighboring chirality. The synthesis of tetrahydrolipstatin using the second approach comprises seven steps from 11 and proceeds in 38 % overall yield.

  DOI：

  10.1021/jo00079a022

文献信息

• Development of an Activity-Based Probe and In Silico Design Reveal Highly Selective Inhibitors for Diacylglycerol Lipase-α in Brain
  作者：Marc P. Baggelaar、Freek J. Janssen、Annelot C. M. van Esbroeck、Hans den Dulk、Marco Allarà、Sascha Hoogendoorn、Ross McGuire、Bogdan I. Florea、Nico Meeuwenoord、Hans van den Elst、Gijsbert A. van der Marel、Jaap Brouwer、Vincenzo Di Marzo、Herman S. Overkleeft、Mario van der Stelt

  DOI：10.1002/anie.201306295

  日期：2013.11.11

  A model method: A strategy that combines a knowledge‐based in silico design approach and the development of novel activity‐based probes (ABPs) for the detection of endogenous diacylglycerol lipase‐α (DAGL‐α) is presented. This approach resulted in the rapid identification of new DAGL‐α inhibitors with high selectivity in the brain proteome. ABPP=activity‐based protein profiling.

  一种模型方法：提出了一种策略，该策略结合了基于知识的计算机设计方法和新的基于活动的探针（ABP）的开发，用于检测内源性二酰基甘油脂肪酶-α（DAGL-α）。这种方法可以快速鉴定出在脑蛋白质组中具有高选择性的新型DAGL-α抑制剂。ABPP =基于活性的蛋白质谱。
• 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.