Methyl 3-bromo-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosonate | 111476-74-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Methyl 3-bromo-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosonate
• 英文别名: methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3-bromo-3,5-dideoxy-β-D-erythro-L-manno-2-nonulopyranosonate；methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3-bromo-3,5-dideoxy-β-D-erythro-L-gluconon-2-ulopyranosonate；methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-3-bromo-D-erythro-β-L-manno-non-2-ulopyranosonate；methyl (2R,3R,4R,5S,6R)-5-acetamido-4-acetyloxy-3-bromo-2-hydroxy-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate
• CAS: 111476-74-5
• 化学式: C₂₀H₂₈BrNO₁₃
• 分子量: 570.345
• InChiKey: WWYGCQUCFFHWPW-CIVJTVJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  190
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Methyl 3-bromo-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosonate 在 吡啶 、 4-二甲氨基吡啶 、 偶氮二异丁腈 、 乙酰氯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 100.0 ℃ 、13.33 kPa 条件下， 反应 88.33h， 生成 methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-3-C-(prop-2′-enyl)-D-glycero-D-galacto-non-2-enonate
  参考文献：
  名称：

  An efficient synthesis of C3 C-alkylated Neu5Ac2en derivatives

  摘要：

  C3-modified Neu5Ac2en derivatives can be used to study the flexible 150-loop region of influenza virus sialidases and also provide a new template for the development of next-generation sialidase inhibitors. This Letter describes an efficient synthetic route towards the large scale synthesis of C3 C-alkylated Neu5Ac2en derivatives. The key intermediate, a 3-eq-allyl-Neu5Ac derivative, is formed by stereoselective addition of the allyl group in an equatorial configuration at C3, regardless of the stereochemistry of the bromohydrin precursor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.12.064
• 作为产物：
  描述：

  (1S,2R)-1-((2R,3R,4S)-3-乙酰氨基-4-乙酰氧基-6-氯-6-(甲氧基羰基 在 disodium hydrogenphosphate 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 、 乙腈 为溶剂， 反应 3.5h， 生成 Methyl 3-bromo-5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosonate
  参考文献：
  名称：

  An efficient synthesis of C3 C-alkylated Neu5Ac2en derivatives

  摘要：

  C3-modified Neu5Ac2en derivatives can be used to study the flexible 150-loop region of influenza virus sialidases and also provide a new template for the development of next-generation sialidase inhibitors. This Letter describes an efficient synthetic route towards the large scale synthesis of C3 C-alkylated Neu5Ac2en derivatives. The key intermediate, a 3-eq-allyl-Neu5Ac derivative, is formed by stereoselective addition of the allyl group in an equatorial configuration at C3, regardless of the stereochemistry of the bromohydrin precursor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.12.064

文献信息

• [EN] ANTI -INFLUENZA AGENTS<br/>[FR] AGENTS ANTIGRIPPAUX
  申请人：UNIV GRIFFITH

  公开号：WO2011006208A1

  公开（公告）日：2011-01-20

  The present invention relates to compounds that selectively inhibit influenza A virus group (1) sialidases and are therefore potential anti-influenza agents.

  本发明涉及选择性抑制流感A病毒群（1）唾液酸酶的化合物，因此是潜在的抗流感药物。
• ANTI-INFLUENZA AGENTS
  申请人：Von Itzstein Mark

  公开号：US20120202877A1

  公开（公告）日：2012-08-09

  The present invention relates to compounds that selectively inhibit influenza A virus group (1) sialidases and are therefore potential anti-influenza agents.

  本发明涉及选择性抑制流感A病毒群（1）唾液酸酶的化合物，因此是潜在的抗流感药物。
• Systematic Syntheses and Inhibitory Activities of Bisubstrate-Type Inhibitors of Sialyltransferases
  作者：Hiroshi Hinou、Xue-Long Sun、Yukishige Ito

  DOI：10.1021/jo030042g

  日期：2003.7.1

  Bisubstrate-type sialyltransferase inhibitors 1/2a-e, having CMP-NeuAc and N-acetyllactosamine (or lactose) moieties connected by an alkanedithiol linker, were synthesized systematically. A uniform synthetic strategy was adopted that consists of consecutive couplings of three components (N-acetyllactosamine or lactose, sialic acid, and CMP), followed by oxidation. Due to the sensitivity of the compounds

  系统合成了具有CMP-NeuAc和N-乙酰基乳糖胺（或乳糖）部分的双底物型唾液酸转移酶抑制剂1 / 2a-e。采用了一种统一的合成策略，该策略包括三个成分（N-乙酰基乳糖胺或乳糖，唾液酸和CMP）的连续偶联，然后进行氧化。由于化合物在碱性条件下的敏感性，最终脱保护需要通过（1）H NMR进行仔细监测。1 / 2a-e对ST6N和ST3N的抑制活性表明，受体部分的结构以及供体和受体部分之间的距离都很重要。
• Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility
  作者：Santosh Rudrawar、Philip S. Kerry、Marie-Anne Rameix-Welti、Andrea Maggioni、Jeffrey C. Dyason、Faith J. Rose、Sylvie van der Werf、Robin J. Thomson、Nadia Naffakh、Rupert J. M. Russell、Mark von Itzstein

  DOI：10.1039/c2ob25627d

  日期：——

  Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can ‘trap’ the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility.

  我们设计了新型 3-C 烷基化-Neu5Ac2en 衍生物，用于靶向具有开放式 150 环的流感病毒表面糖苷酶的扩展活性位点空腔，目前在甲型流感病毒第 1 组（N1、N4、N5、N8）而非第 2 组（N2、N9）表面糖苷酶的 X 射线晶体结构中可以看到这种空腔。这些化合物对 H5N1 和 pdm09 H1N1 sialid 酶的抑制作用优于对 N2 sialid 酶的抑制作用，证明了这些 sialid 酶的 150 环具有相对的灵活性。在与 N8 sialid 酶的复合物中，3-phenylally-Neu5Ac2en 的 C3 取代基占据了 150 腔，而中心环和其余取代基则与未取代模板的活性位点结合。这一类新的抑制剂可以 "捕获 "开放的 150 环形式的硅糖苷酶，应被证明是 150 环灵活性的有用探针。
• Bisubstrate-type inhibitor of sialyltransferases
  作者：Hiroshi Hinou、Xue-Long Sun、Yukishige Ito

  DOI：10.1016/s0040-4039(02)02272-4

  日期：2002.12

  A convergent strategy for the construction of bisubstrate-type sialyltransferase inhibitor (1) was developed. It consists of consecutive coupling of three components (N-acetyllactosamine, sialic acid, and CMP), followed by oxidation and deprotection. As expected, compound 1 showed potent inhibitory activities toward both 2,3-(N)- and 2,6-(N)-sialyltransferase.

  提出了一种构建双底物型唾液酸转移酶抑制剂（1）的收敛策略。它包括三个成分（N-乙酰基乳糖胺，唾液酸和CMP）的连续偶联，然后进行氧化和脱保护。如所预期的，化合物1显示出对2，3-（N）-和2，6-（N）-唾液酸转移酶的有效抑制活性。