3,6-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride | 226382-94-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,6-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride
• 英文别名: 3,6,2′,3′,4′,6′-hexa-O-acetyl-2-deoxy-2-fluoro-α-D-maltosyl fluoride
• CAS: 226382-94-1
• 化学式: C₂₄H₃₂F₂O₁₅
• 分子量: 598.506
• InChiKey: VPWDWUMNGYNFMS-QXNNTSRZSA-N

反应信息

• 作为反应物：
  描述：

  3,6-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride 在 sodium methylate 作用下， 生成 2-deoxy-2-fluoro-α-maltosyl fluoride
  参考文献：
  名称：

  Structural Insight into How Streptomyces coelicolor Maltosyl Transferase GlgE Binds α-Maltose 1-Phosphate and Forms a Maltosyl-enzyme Intermediate

  摘要：

  GlgE (EC 2.4.99.16) is an alpha-maltose 1-phosphate:(1 -> 4)-alpha-D-glucan 4-alpha-D-maltosyltransferase of the CAZy glycoside hydrolase 13_3 family. It is the defining enzyme of a bacterial alpha-glucan biosynthetic pathway and is a genetically validated anti-tuberculosis target. It catalyzes the alpha-retaining transfer of maltosyl units from alpha-maltose 1-phosphate to maltooligosaccharides and is predicted to use a double-displacement mechanism. Evidence of this mechanism was obtained using a combination of site-directed mutagenesis of Streptomyces coelicolor GlgE isoform I, substrate analogues, protein crystallography, and mass spectrometry. The X-ray structures of alpha-maltose 1-phosphate bound to a D394A mutein and a beta-2-deoxy-2-fluoromaltosyl-enzyme intermediate with a E423A mutein were determined. There are few examples of CAZy glycoside hydrolase family 13 members that have had their glycosyl-enzyme intermediate structures determined, and none before now have been obtained with a 2-deoxy-2-fluoro substrate analogue. The covalent modification of Asp394 was confirmed using mass spectrometry. A similar modification of wild-type GlgE proteins from S. coelicolor and Mycobacterium tuberculosis was also observed. Small-angle X-ray scattering of the M. tuberculosis enzyme revealed a homodimeric assembly similar to that of the S. coelicolor enzyme but with slightly differently oriented monomers. The deeper understanding of the structure function relationships of S. coelicolor GlgE will aid the development of inhibitors of the M. tuberculosis enzyme.

  DOI：

  10.1021/bi500183c
• 作为产物：
  描述：

  [(2R,3S,4R)-4-乙酰氧基-3-[(2R,3R,4S,5R,6R)-3,4,5-三乙酰氧基-6-(乙酰氧基甲基)四氢吡喃-2-基]氧基-3,4-二氢-2H-吡喃-2-基]甲基乙酸酯 在 二氟代氙 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以21%的产率得到3,6-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride
  参考文献：
  名称：

  Structural Insight into How Streptomyces coelicolor Maltosyl Transferase GlgE Binds α-Maltose 1-Phosphate and Forms a Maltosyl-enzyme Intermediate

  摘要：

  GlgE (EC 2.4.99.16) is an alpha-maltose 1-phosphate:(1 -> 4)-alpha-D-glucan 4-alpha-D-maltosyltransferase of the CAZy glycoside hydrolase 13_3 family. It is the defining enzyme of a bacterial alpha-glucan biosynthetic pathway and is a genetically validated anti-tuberculosis target. It catalyzes the alpha-retaining transfer of maltosyl units from alpha-maltose 1-phosphate to maltooligosaccharides and is predicted to use a double-displacement mechanism. Evidence of this mechanism was obtained using a combination of site-directed mutagenesis of Streptomyces coelicolor GlgE isoform I, substrate analogues, protein crystallography, and mass spectrometry. The X-ray structures of alpha-maltose 1-phosphate bound to a D394A mutein and a beta-2-deoxy-2-fluoromaltosyl-enzyme intermediate with a E423A mutein were determined. There are few examples of CAZy glycoside hydrolase family 13 members that have had their glycosyl-enzyme intermediate structures determined, and none before now have been obtained with a 2-deoxy-2-fluoro substrate analogue. The covalent modification of Asp394 was confirmed using mass spectrometry. A similar modification of wild-type GlgE proteins from S. coelicolor and Mycobacterium tuberculosis was also observed. Small-angle X-ray scattering of the M. tuberculosis enzyme revealed a homodimeric assembly similar to that of the S. coelicolor enzyme but with slightly differently oriented monomers. The deeper understanding of the structure function relationships of S. coelicolor GlgE will aid the development of inhibitors of the M. tuberculosis enzyme.

  DOI：

  10.1021/bi500183c

文献信息

• Studies on the Reaction of D-Glucal and its Derivatives with 1-Chloromethyl-4-Fluoro-1,4-Diazoniabicyclo[2.2.2]Octane Salts
  作者：J. Ortner、M. Albert、H. Weber、K. Dax

  DOI：10.1080/07328309908543997

  日期：1999.1.1

  ABSTRACT The reaction of D-glucal and its derivatives with the electrophilic N-F-fluorination reagents F-TEDA tetrafluoroborate and triflate was studied by means of 19F NMR spectroscopy. In all cases mixtures of 2-deoxy-2-fluoro-D-gluco- and -D-mannopyranose derivatives were formed, the ratio of which was dependent on the nature of the O-protecting groups. Concerning the products arising from the direct

  摘要利用19F NMR光谱研究了D-葡萄糖及其衍生物与亲电NF-氟化试剂F-TEDA四氟硼酸酯和三氟甲磺酸酯的反应。在所有情况下，均形成2-脱氧-2-氟-D-葡萄糖-和-D-甘露吡喃糖衍生物的混合物，其比例取决于O-保护基团的性质。关于直接通过双键添加试剂产生的产物，D-葡萄糖构型的化合物（13-20）通常显示出比其D-甘露聚糖对应物（21-28）更高的水解速率。仅当形成单个端基异构体（例如2,4-二硝基苯基糖苷29e / 37e和二糖氟化物35d / 43d）或过氧乙酸酯（例如29f / 37f）时，才能实现产品分离。
• Syntheses of 2-deoxy-2-fluoro mono- and oligo-saccharide glycosides from glycals and evaluation as glycosidase inhibitors
  作者：John D. McCarter、Michael J. Adam、Curtis Braun、Mark Namchuk、Dedreia Tull、Stephen G. Withers

  DOI：10.1016/0008-6215(93)84061-a

  日期：1993.10

  Several fluorinated oligosaccharides, including 2-deoxy-2-fluoro derivatives of cellobiose, maltose, and maltotriose were synthesized by the action of fluorine or acetyl hypofluorite on the corresponding glycal peracetates. Temperature effects on the stereoselectivities of these reactions were examined. Addition of acetyl hypofluorite to several 2-substituted glycals in the gluco or galacto series gave 2,2-disubstituted arabino- or lyxo-hexose derivatives; 3,4,6-tri-O-acetyl-2-fluoro-D-glucal or the analogous galactal yielded 2-deoxy-2,2-difluoro arabino- or lyxo-hexose peracetates, whereas 2-acetoxy-3,4,6-tri-O-acetyl-D-glucal or the analogous galactal gave 2(R)-2-acetoxy-2-fluoro-arabino- or lyxo-hexose peracetates, respectively. 2-Acetamido-3,4,6-tri-O-acetyl-D-glucal gave 2(R)-2-acetamido-2-acetoxy-3,4,6-tri-O-acetyl-alpha-D-arabino-hexopyranosyl fluoride. 2,4-Dinitrophenyl 2-deoxy-2-fluoro-beta-cellobioside was an inactivator of the exoglucanase from Cellulomonas fimi while 2-deoxy-2-fluoro-alpha-maltosyl and alpha-maltotriosyl fluorides were slow substrates of human pancreatic alpha-amylase and rabbit muscle glycogen debranching enzyme, respectively.