Methyl (S)-3-<(tert-butyldimethylsilyl)oxy>-4-(tosyloxy)butanoate | 169522-69-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl (S)-3-<(tert-butyldimethylsilyl)oxy>-4-(tosyloxy)butanoate
• 英文别名: methyl (3S)-3-[tert-butyl(dimethyl)silyl]oxy-4-(4-methylphenyl)sulfonyloxybutanoate
• CAS: 169522-69-4
• 化学式: C₁₈H₃₀O₆SSi
• 分子量: 402.584
• InChiKey: BLPFXDOVCLNGBR-HNNXBMFYSA-N

物化性质

• 沸点：
  460.5±40.0 °C(Predicted)
• 密度：
  1.103±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.65
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl (S)-3-<(tert-butyldimethylsilyl)oxy>-4-(tosyloxy)butanoate 在 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 二甲基亚砜 、 异丙醇 、 甲苯 为溶剂， 反应 4.5h， 生成 (S)-3-<(tert-Butyldimethylsilyl)oxy>-4-cyanobutanal diisopropyl acetal
  参考文献：
  名称：

  The First Total Synthesis of (-)-Lipstatin

  摘要：

  A key step in the first total synthesis of the potent pancreatic lipase inhibitor (-)-lipstatin (1) is a diastereoselective Lewis acid-promoted [2 + 2] cycloaddition reaction between n-hexyl(trimethylsilyl)ketene (4) and (R)-(-)-(Z,Z)-3-[(tert-butyldimethylsilyl)oxy]5,8-tetradecadienal (3), which is prepared from dimethyl (S)-(-)-malate.

  DOI：

  10.1021/jo00127a045
• 作为产物：
  描述：

  L-苹果酸二甲酯 生成 Methyl (S)-3-<(tert-butyldimethylsilyl)oxy>-4-(tosyloxy)butanoate
  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。
• 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.
• The β-lactone route to α,β-unsaturated δ-lactones. Total syntheses of (±)-goniothalamin and (−)-massoialactone
  作者：Lycia Fournier、Philip Kocienski、Jean-Marc Pons

  DOI：10.1016/j.tet.2003.11.094

  日期：2004.2

  The HF-induced translactonization of 2'-silyloxy-3-trimethylsilyl-2-oxetanones, obtained through Lewis acid-promoted [2+2] cycloaddition between beta-silyloxyaldehydes and trimethylsilylsilylketene, into alpha,beta-unsaturated delta-lactones is applied to the syntheses of (+/-)-goniothalamin and (-)-massoialactone. (C) 2003 Elsevier Ltd. All rights reserved.
• The First Total Synthesis of (-)-Lipstatin
  作者：Agnes Pommier、Jean-Marc Pons、Philip J. Kocienski

  DOI：10.1021/jo00127a045

  日期：1995.11

  A key step in the first total synthesis of the potent pancreatic lipase inhibitor (-)-lipstatin (1) is a diastereoselective Lewis acid-promoted [2 + 2] cycloaddition reaction between n-hexyl(trimethylsilyl)ketene (4) and (R)-(-)-(Z,Z)-3-[(tert-butyldimethylsilyl)oxy]5,8-tetradecadienal (3), which is prepared from dimethyl (S)-(-)-malate.
• 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.