p-tolyl 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-thioglucopyranoside | 671809-80-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: p-tolyl 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-thioglucopyranoside
• CAS: 671809-80-6
• 化学式: C₃₄H₃₅N₃O₄S
• 分子量: 581.736
• InChiKey: LPLQEOSOGHPWID-SLXQPGMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.88
• 重原子数：
  42.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.68
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  p-tolyl 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-thioglucopyranoside 在 N-碘代丁二酰亚胺 作用下， 以 水 、 丙酮 为溶剂， 生成 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose
  参考文献：
  名称：

  Synthesis and High-Throughput Screening of N-Acetyl-β-hexosaminidase Inhibitor Libraries Targeting Osteoarthritis

  摘要：

  C1 Nitrogen iminocyclitols are potent inhibitors of N-acetyl-beta-hexosaminidases. Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-mannosamine hydrochloride and the microbial oxidation product of fructose. A diversity-oriented synthetic strategy was then performed by coupling these core structures with various aldehydes, carboxylic acids, and alkynes to generate three separate libraries. High-throughput screening of the generated libraries with human N-acetyl-beta-hexosaminidases produced only moderate inhibitory activities. However, the synthetic approach and screening strategy for these compounds will be applied to develop new potent inhibitors of human N-acetyl-beta-hexosaminidases, particularly when combined with the structural information of these enzymes.

  DOI：

  10.1021/jo049355h
• 作为产物：
  描述：

  p-tolyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-thio-α-D-glucopyranoside 在 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 p-tolyl 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-thioglucopyranoside
  参考文献：
  名称：

  Synthesis and High-Throughput Screening of N-Acetyl-β-hexosaminidase Inhibitor Libraries Targeting Osteoarthritis

  摘要：

  C1 Nitrogen iminocyclitols are potent inhibitors of N-acetyl-beta-hexosaminidases. Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-mannosamine hydrochloride and the microbial oxidation product of fructose. A diversity-oriented synthetic strategy was then performed by coupling these core structures with various aldehydes, carboxylic acids, and alkynes to generate three separate libraries. High-throughput screening of the generated libraries with human N-acetyl-beta-hexosaminidases produced only moderate inhibitory activities. However, the synthetic approach and screening strategy for these compounds will be applied to develop new potent inhibitors of human N-acetyl-beta-hexosaminidases, particularly when combined with the structural information of these enzymes.

  DOI：

  10.1021/jo049355h

文献信息

• Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions
  作者：Chun‐Wei Chang、Mei‐Huei Lin、Chieh‐Kai Chan、Kuan‐Yu Su、Chia‐Hui Wu、Wei‐Chih Lo、Sarah Lam、Yu‐Ting Cheng、Pin‐Hsuan Liao、Chi‐Huey Wong、Cheng‐Chung Wang

  DOI：10.1002/anie.202013909

  日期：2021.5.25

  (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure

  糖基化反应的立体选择性和产率至关重要，但不可预测。我们已经开发了一个亲核亲核常数（Aka）数据库，用于量化受空间，电子和结构效应影响的糖基化中羟基的亲核性，从而在实验和计算机算法之间建立联系。各种碳水化合物分子上的羟基之间的细微反应性差异可以由Aka定义，Aka可以通过简单便捷的自动化系统轻松访问，以确保高重现性和准确性。通过设计的软件程序“ GlycoComputer”可以组织和处理各种具有明确反应性和启动子的糖基化供体和受体，从而无需复杂的计算过程即可预测糖基化反应。通过随机森林算法进一步验证了Aka的重要性，并通过合成Lewis A骨架测试了适用性，表明可以准确估计立体选择性和产率。
• Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity
  作者：Chun‐Wei Chang、Chia‐Hui Wu、Mei‐Huei Lin、Pin‐Hsuan Liao、Chun‐Chi Chang、Hsiao‐Han Chuang、Su‐Ching Lin、Sarah Lam、Ved Prakash Verma、Chao‐Ping Hsu、Cheng‐Chung Wang

  DOI：10.1002/anie.201906297

  日期：2019.11.18

  Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates:

  尽管数十年来进行了大量的努力，但立体控制的化学糖基化仍然是一个主要挑战，到目前为止，仍然主要依靠反复试验。现在表明，硫糖苷的相对反应性值（RRV）是根据四种受体揭示立体选择性的指标。机理研究表明，该反应由两种不同的中间体控制：糖基三氟甲磺酸酯和来自N-卤代琥珀酰亚胺（NXS）/ TfOH的糖基卤化物。糖基卤化物的形成与α-糖苷的产生高度相关。这些发现使得能够通过使用RRV作为α/β-选择性指示剂来预见糖基化反应，并且为立体控制糖基化开发了指导方针和规则。
• Aminoglycoside antibiotics as novel anti-infective agents
  申请人：——

  公开号：US20040058880A1

  公开（公告）日：2004-03-25

  This invention relates to novel aminoglycoside compounds having antibacterial and anti-infective activity and to pharmaceutical compositions, methods of making and methods of treatment employing the same.

  这项发明涉及具有抗菌和抗感染活性的新型氨基糖苷化合物，以及包括这些化合物的药物组合物、制备方法和治疗方法。
• Regioselective Benzylation of Azido-Containing Monosaccharides
  作者：Xin-Shan Ye、Qiu-Hua Fan、Qin Li、Li-He Zhang

  DOI：10.1055/s-2006-939681

  日期：——

  A regioselective benzylation or p-methoxybenzylation of diols in azido-containing monosaccharide derivatives was reported, and the reaction was performed under the conventional reaction conditions (NaH/BnBr in DMF). The hydroxyl functionality adjacent to the azido group was benzylated selectively in good yields.

  报道了含叠氮基单糖衍生物中二醇的区域选择性苯甲基化或对甲氧基苯甲基化，并且该反应在常规反应条件（NaH/BnBr在DMF中）下进行。与叠氮基相邻的羟基官能团以良好的产率选择性地被苄基化。
• A Bioactive Synthetic Outer‐Core Oligosaccharide Derived from a <i>Klebsiella pneumonia</i> Lipopolysaccharide for Bacteria Recognition
  作者：Dushen Chen、Akhilesh K. Srivastava、Justyna Dubrochowska、Lin Liu、Tiehai Li、Joseph P. Hoffmann、Jay K. Kolls、Geert‐Jan Boons

  DOI：10.1002/chem.202203408

  日期：——

  A chemical synthesised outer core tetra- and pentasaccharide derived from the lipopolysaccharide of K. pneumoniae conjugated to the carrier proteins CRM197 and BSA elicited in mice antibodies that recognized isolated LPS as well as various strains of K. pneumoniae demonstrating they can induce relevant antigenic responses.

  化学合成的外核四糖和五糖源自肺炎克雷伯菌的脂多糖，与载体蛋白 CRM 197和 BSA 结合，在小鼠体内引发识别分离的 LPS 以及各种肺炎克雷伯菌菌株的抗体，证明它们可以诱导相关的抗原反应。