phenethyl 2-azido-3-O-benzoyl-6-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-glucopyranoside | 1202785-46-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: phenethyl 2-azido-3-O-benzoyl-6-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-glucopyranoside
• 英文别名: 2'-(phenyl)ethyl 2-azido-3-O-benzoyl-6-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-glucopyranoside；[(2R,3S,4R,5R,6S)-5-azido-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-hydroxy-6-(2-phenylethoxy)oxan-4-yl] benzoate
• CAS: 1202785-46-3
• 化学式: C₃₇H₄₁N₃O₆Si
• 分子量: 651.835
• InChiKey: IMUTWDFFCDTFHF-CLNUGPORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.81
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  phenethyl 2-azido-3-O-benzoyl-6-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-glucopyranoside 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl (4R)-4-[[(3aR,7aS)-7a-hydroxy-3,6-dioxo-2,4,5,7-tetrahydro-1H-inden-3a-yl]methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  Biological Diversity from a Structurally Diverse Library: Systematically Scanning Conformational Space Using a Pyranose Scaffold

  摘要：

  Success in discovering bioactive peptide mimetics is often limited by the difficulties in correctly transposing known binding elements of the active peptide onto a small and metabolically more stable scaffold while maintaining bioactivity. Here we describe a scanning approach using a library of pyranose-based peptidomimetics that is structurally diverse in a systematic manner, designed to cover all possible conformations of tripeptide motifs containing two aromatic groups and one positive charge. Structural diversity was achieved by efficient selection of various chemoforms, characterized by a choice of pyranose scaffold of defined chirality and substitution pattern. A systematic scanning library of 490 compounds was thus designed, produced, and screened in vitro for activity at the somatostatin (sst(1-5)) and melanin-concentrating hormone (MCH1) receptors. Bioactive compounds were found for each target, with specific chemoform preferences identified in each case, which can be used to guide follow-on drug discovery projects without the need for scaffold hopping.

  DOI：

  10.1021/jm1002777
• 作为产物：
  描述：

  tert-butyl (4R)-4-[[(3aR,7aS)-7a-hydroxy-3,6-dioxo-2,4,5,7-tetrahydro-1H-inden-3a-yl]methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 phenethyl 2-azido-3-O-benzoyl-6-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-glucopyranoside
  参考文献：
  名称：

  A Versatile Synthetic Approach toward Diversity Libraries using Monosaccharide Scaffolds

  摘要：

  The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type Of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build oil 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied oil glucose mid allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations oil a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics.

  DOI：

  10.1021/jo9021919

文献信息

• A Versatile Synthetic Approach toward Diversity Libraries using Monosaccharide Scaffolds
  作者：Giang Le Thanh、Giovanni Abbenante、George Adamson、Bernd Becker、Chris Clark、Glenn Condie、Tania Falzun、Matthias Grathwohl、Praveer Gupta、Michael Hanson、Ngoc Huynh、Peter Katavic、Krystle Kuipers、Ann Lam、Ligong Liu、Maretta Mann、Jeff Mason、Declan McKeveney、Craig Muldoon、Andrew Pearson、Premraj Rajaratnam、Sarah Ryan、Gerry Tometzki、Geraldine Verquin、Jennifer Waanders、Michael West、Neil Wilcox、Norbert Wimmer、Annika Yau、Johannes Zuegg、Wim Meutermans

  DOI：10.1021/jo9021919

  日期：2010.1.1

  The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type Of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build oil 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied oil glucose mid allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations oil a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics.
• Biological Diversity from a Structurally Diverse Library: Systematically Scanning Conformational Space Using a Pyranose Scaffold
  作者：Giovanni Abbenante、Bernd Becker、Sébastien Blanc、Chris Clark、Glenn Condie、Graeme Fraser、Matthias Grathwohl、Judy Halliday、Senka Henderson、Ann Lam、Ligong Liu、Maretta Mann、Craig Muldoon、Andrew Pearson、Rajaratnam Premraj、Tracie Ramsdale、Tony Rossetti、Karl Schafer、Giang Le Thanh、Gerald Tometzki、Frank Vari、Géraldine Verquin、Jennifer Waanders、Michael West、Norbert Wimmer、Annika Yau、Johannes Zuegg、Wim Meutermans

  DOI：10.1021/jm1002777

  日期：2010.8.12

  Success in discovering bioactive peptide mimetics is often limited by the difficulties in correctly transposing known binding elements of the active peptide onto a small and metabolically more stable scaffold while maintaining bioactivity. Here we describe a scanning approach using a library of pyranose-based peptidomimetics that is structurally diverse in a systematic manner, designed to cover all possible conformations of tripeptide motifs containing two aromatic groups and one positive charge. Structural diversity was achieved by efficient selection of various chemoforms, characterized by a choice of pyranose scaffold of defined chirality and substitution pattern. A systematic scanning library of 490 compounds was thus designed, produced, and screened in vitro for activity at the somatostatin (sst(1-5)) and melanin-concentrating hormone (MCH1) receptors. Bioactive compounds were found for each target, with specific chemoform preferences identified in each case, which can be used to guide follow-on drug discovery projects without the need for scaffold hopping.