p-tolyl 2-deoxy-2-azido-3-O-benzyl-4,6-O-benzylidene-1-thio-α-D-glucopyranoside | 1235137-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: p-tolyl 2-deoxy-2-azido-3-O-benzyl-4,6-O-benzylidene-1-thio-α-D-glucopyranoside
• 英文别名: p-tolyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-D-thioglucopyranoside
• CAS: 1235137-50-4
• 化学式: C₂₇H₂₇N₃O₄S
• 分子量: 489.595
• InChiKey: LSFXJSWSDKKNNC-ZRRJEQDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.19
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 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-deoxy-2-azido-3-O-benzyl-4,6-O-benzylidene-1-thio-α-D-glucopyranoside 在 吡啶 、 咪唑 、 N-溴代丁二酰亚胺(NBS) 、 三氟甲磺酸三甲基硅酯 、 palladium on activated charcoal 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 丙酮 、 甲苯 为溶剂， 反应 46.0h， 生成 GlcA(b1-4)GlcNAc
  参考文献：
  名称：

  OLIGOSACCHARIDE LINKER, LINKER-PAYLOAD COMPRISING THE SAME AND GLYCAN CHAIN-REMODELED ANTIBODY-DRUG CONJUGATE, PREPARATION METHODS AND USES THEREOF

  摘要：

  The present disclosure further relates to a linker-payload compound including an oligosaccharide group, especially a disaccharide group, where the oligosaccharide group is linked to the remainder of the compound by an amide bond. The present disclosure further relates to an antibody-drug conjugate (ADC) containing the linker-payload compound, where the glycan chain in an antibody is remodeled with the oligosaccharide moiety in the linker-payload compound. The present disclosure further relates to preparation methods and use of the above-mentioned substances.

  公开号：

  US20240082419A1
• 作为产物：
  描述：

  p-tolyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-thio-α-D-glucopyranoside 在 甲醇 、 sodium methylate 、 sodium hydride 、 对甲苯磺酸 作用下， 以 乙腈 为溶剂， 反应 56.0h， 生成 p-tolyl 2-deoxy-2-azido-3-O-benzyl-4,6-O-benzylidene-1-thio-α-D-glucopyranoside
  参考文献：
  名称：

  OLIGOSACCHARIDE LINKER, LINKER-PAYLOAD COMPRISING THE SAME AND GLYCAN CHAIN-REMODELED ANTIBODY-DRUG CONJUGATE, PREPARATION METHODS AND USES THEREOF

  摘要：

  The present disclosure further relates to a linker-payload compound including an oligosaccharide group, especially a disaccharide group, where the oligosaccharide group is linked to the remainder of the compound by an amide bond. The present disclosure further relates to an antibody-drug conjugate (ADC) containing the linker-payload compound, where the glycan chain in an antibody is remodeled with the oligosaccharide moiety in the linker-payload compound. The present disclosure further relates to preparation methods and use of the above-mentioned substances.

  公开号：

  US20240082419A1

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。
• Rational design and synthesis of potent aminoglycoside antibiotics against resistant bacterial strains
  作者：Ri-Bai Yan、Min Yuan、Yanfen Wu、Xuefu You、Xin-Shan Ye

  DOI：10.1016/j.bmc.2010.11.065

  日期：2011.1

  designed and synthesized. A convenient approach to the construction of kanamycin derivatives, in which the C4′-position on ring I of neamine moiety was modified, was developed. Most synthetic analogues exhibited good to excellent antibiotic activity against some typical drug-resistant bacteria. The disclosed results suggested that the C4′-position of aminoglycosides such as kanamycin may be an ideal site

  根据生物大分子-氨基糖苷复合物的结构信息，合理设计和合成了一系列卡那霉素B类似物。开发了一种方便的卡那霉素衍生物的构建方法，其中对氨基胺部分的环I的C4'位置进行了修饰。大多数合成类似物对某些典型的耐药细菌均表现出良好或优异的抗生素活性。公开的结果表明，氨基糖苷例如卡那霉素的C4'-位可能是用于修饰以获得新的对修饰酶具有抗性的氨基糖苷抗生素的理想位点。
• Mapping Mechanisms in Glycosylation Reactions with Donor Reactivity: Avoiding Generation of Side Products
  作者：Chun-Wei Chang、Mei-Huei Lin、Chia-Hui Wu、Tsun-Yi Chiang、Cheng-Chung Wang

  DOI：10.1021/acs.joc.0c01313

  日期：2020.12.18

  The glycosylation reaction, which is key for the studies on glycoscience, is challenging due to its complexity and intrinsic side reactions. Thioglycoside is one of the most widely used glycosyl donors in the synthesis of complex oligosaccharides. However, one of the challenges is its side reactions, which lower its yield and limits its efficiency, thereby requiring considerable effort in the optimization

  糖基化反应是糖科学研究的关键，由于其复杂性和固有的副反应，因此具有挑战性。硫代糖苷是复杂寡糖合成中使用最广泛的糖基供体之一。但是，挑战之一是它的副反应，这会降低其收率并限制其效率，因此需要在优化过程中付出大量努力。在这里，我们报道了一个多方面的实验方法，揭示了副反应的行为，例如分子间硫糖苷转化和氮-糖基琥珀酰亚胺，通过糖基中间体。我们的机制建议得到了低温NMR研究的支持，该研究可通过利用相对反应性值进行进一步映射。因此，我们还提出了我们的发现以抑制副产物的生成，从而解决了实现高产率糖基化反应的这一特殊问题。
• 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。