N-[(2S,3R,4R,5S,6R)-6-(tert-Butyl-diphenyl-silanyloxymethyl)-4,5-dihydroxy-2-methoxy-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide | 591218-64-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[(2S,3R,4R,5S,6R)-6-(tert-Butyl-diphenyl-silanyloxymethyl)-4,5-dihydroxy-2-methoxy-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide
• 英文别名: TfaNH(-2d)[TBDPS(-6)]a-Glc1Me；N-[(2S,3R,4R,5S,6R)-6-[[tert-butyl(diphenyl)silyl]oxymethyl]-4,5-dihydroxy-2-methoxyoxan-3-yl]-2,2,2-trifluoroacetamide
• CAS: 591218-64-3
• 化学式: C₂₅H₃₂F₃NO₆Si
• 分子量: 527.613
• InChiKey: DKZXCKDBSQOCRN-LMYCIYFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  97.2
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[(2S,3R,4R,5S,6R)-6-(tert-Butyl-diphenyl-silanyloxymethyl)-4,5-dihydroxy-2-methoxy-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.75h， 生成 N-[(1S,2R,4S,5R,6S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-4-methoxy-3,7-dioxa-bicyclo[4.1.0]hept-5-yl]-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  Synthesis of Twod‐Glucosamine Derived 3,4‐Epoxides as Potential Scaffolds for Combinatorial Chemistry

  摘要：

  Combinatorial chemistry allows the synthesis of libraries of compounds by combination of building blocks or by combinatorial elaboration of a central scaffold.([1,2]) Carbohydrates hold great promise as scaffolds due to their high degree of functionalization, relative conformational rigidity, commercial availability of many stereoisomeric forms, and their well-described chemistry. Hirschmann, Nicolaou, Smith, and their coworkers pioneered the use of carbohydrates as scaffolds in their design and synthesis Of beta-D-glucose derived non-peptide peptidomimetics of the peptide hormone somatostatin (SRIF).([3,4]) However, only relatively few examples on the application of carbohydrates as scaffolds in combinatorial chemistry have been described.([5-11]) For example, Brill et al. anchored a 1,6-anhydro-beta-D-glucopyranoside (levoglucosan) derived epoxide to a solid support and introduced diversity by opening of the support-bound 2,3-epoxide.([9]) Hirschmann et al. employed the opening of a D-glucose derived 1,2-epoxide with a thiol in one of the initial steps towards the synthesis of a library of D-glucose derived compounds. ([10])We reasoned that introduction of all substituents by O-acylation or carbamoylation would give final products with too high a degree of conformational freedom. To introduce substituents directly on the carbohydrate ring and to keep protecting group manipulations on the resin-bound carbohydrate scaffold to a minimum, we decided to prepare a scaffold in which diversity would be introduced by opening of an epoxide. Also, it was a requirement that the scaffold should contain nitrogen, as amines are found in many pharmacologically relevant molecules, e.g., CNS active compounds. We chose inexpensive D-glucosamine as starting material, to prepare a 3,4-epoxide, and to block the C-1 as the methyl glycoside (Scheme 1). Both solution and solid-phase strategies were envisioned; for the solid-phase strategy, the amine could serve as a convenient point for anchoring to a solid support through a Backbone Amide Linker (BAL). ([12,13]) Here we present the synthesis of two new D-glucosamine derived amino epoxides and preliminary studies on opening of one of the epoxides in solution.First, methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside, 1, easily accessible by Fischer glycosylation, was N-deacetylated by treatment with hydrazine to give known methyl 2-amino-2-deoxy-alpha-D-glucopyranoside 2 (Scheme 1). The N-acetyl group served well here as it was stable to Fischer glycosylation conditions; however, it had to be exchanged with a more labile N-trifluoroacetyl group to allow final deprotection.[GRAPHICS]

  DOI：

  10.1081/car-120021699
• 作为产物：
  描述：

  methyl 2-amino-2-deoxy-α-D-glucopyranoside 在 咪唑 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 N-[(2S,3R,4R,5S,6R)-6-(tert-Butyl-diphenyl-silanyloxymethyl)-4,5-dihydroxy-2-methoxy-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  Synthesis of Twod‐Glucosamine Derived 3,4‐Epoxides as Potential Scaffolds for Combinatorial Chemistry

  摘要：

  Combinatorial chemistry allows the synthesis of libraries of compounds by combination of building blocks or by combinatorial elaboration of a central scaffold.([1,2]) Carbohydrates hold great promise as scaffolds due to their high degree of functionalization, relative conformational rigidity, commercial availability of many stereoisomeric forms, and their well-described chemistry. Hirschmann, Nicolaou, Smith, and their coworkers pioneered the use of carbohydrates as scaffolds in their design and synthesis Of beta-D-glucose derived non-peptide peptidomimetics of the peptide hormone somatostatin (SRIF).([3,4]) However, only relatively few examples on the application of carbohydrates as scaffolds in combinatorial chemistry have been described.([5-11]) For example, Brill et al. anchored a 1,6-anhydro-beta-D-glucopyranoside (levoglucosan) derived epoxide to a solid support and introduced diversity by opening of the support-bound 2,3-epoxide.([9]) Hirschmann et al. employed the opening of a D-glucose derived 1,2-epoxide with a thiol in one of the initial steps towards the synthesis of a library of D-glucose derived compounds. ([10])We reasoned that introduction of all substituents by O-acylation or carbamoylation would give final products with too high a degree of conformational freedom. To introduce substituents directly on the carbohydrate ring and to keep protecting group manipulations on the resin-bound carbohydrate scaffold to a minimum, we decided to prepare a scaffold in which diversity would be introduced by opening of an epoxide. Also, it was a requirement that the scaffold should contain nitrogen, as amines are found in many pharmacologically relevant molecules, e.g., CNS active compounds. We chose inexpensive D-glucosamine as starting material, to prepare a 3,4-epoxide, and to block the C-1 as the methyl glycoside (Scheme 1). Both solution and solid-phase strategies were envisioned; for the solid-phase strategy, the amine could serve as a convenient point for anchoring to a solid support through a Backbone Amide Linker (BAL). ([12,13]) Here we present the synthesis of two new D-glucosamine derived amino epoxides and preliminary studies on opening of one of the epoxides in solution.First, methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside, 1, easily accessible by Fischer glycosylation, was N-deacetylated by treatment with hydrazine to give known methyl 2-amino-2-deoxy-alpha-D-glucopyranoside 2 (Scheme 1). The N-acetyl group served well here as it was stable to Fischer glycosylation conditions; however, it had to be exchanged with a more labile N-trifluoroacetyl group to allow final deprotection.[GRAPHICS]

  DOI：

  10.1081/car-120021699

文献信息

• Synthesis of Two<scp>d</scp>‐Glucosamine Derived 3,4‐Epoxides as Potential Scaffolds for Combinatorial Chemistry
  作者：Lars Svejgaard、Henrik Fuglsang、Peter B. Jensen、Nicholas M. Kelly、Henrik Pedersen、Kim Andersen、Thomas Ruhland、Knud J. Jensen

  DOI：10.1081/car-120021699

  日期：2003.1.6

  Combinatorial chemistry allows the synthesis of libraries of compounds by combination of building blocks or by combinatorial elaboration of a central scaffold.([1,2]) Carbohydrates hold great promise as scaffolds due to their high degree of functionalization, relative conformational rigidity, commercial availability of many stereoisomeric forms, and their well-described chemistry. Hirschmann, Nicolaou, Smith, and their coworkers pioneered the use of carbohydrates as scaffolds in their design and synthesis Of beta-D-glucose derived non-peptide peptidomimetics of the peptide hormone somatostatin (SRIF).([3,4]) However, only relatively few examples on the application of carbohydrates as scaffolds in combinatorial chemistry have been described.([5-11]) For example, Brill et al. anchored a 1,6-anhydro-beta-D-glucopyranoside (levoglucosan) derived epoxide to a solid support and introduced diversity by opening of the support-bound 2,3-epoxide.([9]) Hirschmann et al. employed the opening of a D-glucose derived 1,2-epoxide with a thiol in one of the initial steps towards the synthesis of a library of D-glucose derived compounds. ([10])We reasoned that introduction of all substituents by O-acylation or carbamoylation would give final products with too high a degree of conformational freedom. To introduce substituents directly on the carbohydrate ring and to keep protecting group manipulations on the resin-bound carbohydrate scaffold to a minimum, we decided to prepare a scaffold in which diversity would be introduced by opening of an epoxide. Also, it was a requirement that the scaffold should contain nitrogen, as amines are found in many pharmacologically relevant molecules, e.g., CNS active compounds. We chose inexpensive D-glucosamine as starting material, to prepare a 3,4-epoxide, and to block the C-1 as the methyl glycoside (Scheme 1). Both solution and solid-phase strategies were envisioned; for the solid-phase strategy, the amine could serve as a convenient point for anchoring to a solid support through a Backbone Amide Linker (BAL). ([12,13]) Here we present the synthesis of two new D-glucosamine derived amino epoxides and preliminary studies on opening of one of the epoxides in solution.First, methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside, 1, easily accessible by Fischer glycosylation, was N-deacetylated by treatment with hydrazine to give known methyl 2-amino-2-deoxy-alpha-D-glucopyranoside 2 (Scheme 1). The N-acetyl group served well here as it was stable to Fischer glycosylation conditions; however, it had to be exchanged with a more labile N-trifluoroacetyl group to allow final deprotection.[GRAPHICS]