New Catalytic Methods for the Synthesis of Biomedically Relevant Carbohydrates

合成生物医学相关碳水化合物的新催化方法

• 批准号: 9391514
• 负责人: Maciej Walczak
• 金额: $ 30.8万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9391514
• 关键词: Address; Affect; Air; Alcohols; Biological; Biological Process; Biology; Carbohydrates; Chemicals; Complex; Coupling; Development; Diagnostic; Disaccharides; Elements; Glycoconjugates; Glycosides; Goals; Knowledge; Ligands; Medical; Medicine; Methods; Molecular Structure; Mono-S; Nature; Oligosaccharides; Organic Synthesis; Outcome; Oxidants; Pharmaceutical Preparations; Polysaccharides; Preparation; Process; Property; Protocols documentation; Reaction; Reagent; Research Personnel; Role; Series; Signal Transduction; Solvents; Speed; Standardization; Technology; Testing; Therapeutic; Time; Training; Vaccines; Viral; Work; antitumor drug; base; bioactive natural products; carbohydrate structure; catalyst; chemical synthesis; diabetic; drug candidate; glycosylation; innovation; new technology; novel; novel diagnostics; prevent; programs; small molecule; stannane; tool

PROJECT SUMMARY/ABSTRACT Carbohydrates (also known as saccharides or glycans) occupy a central role among biomolecules due to their participation in a number of signaling and recognition processes in biology. Moreover, carbohydrates are essential structural components of numerous vaccines, anti-diabetic and anti-viral drugs, and anti-tumor drug candidates. Despite significant advances in chemical glycosylation methods, general technologies which offer a precise control of anomeric configuration of the glycosidic bond are in demand. In this proposal we aim to develop methods and strategies for efficient and practical synthesis of bioactive oligosaccharides. In Aim 1, we will expand the toolset of nucleophilic glycosyl donors. In Aim 2, we will develop and apply oxidative glycosylation method for the preparation of oligosaccharides with defined anomeric configuration. This novel method will establish a robust protocol for which the configuration of the anomeric bond is pre-defined in the configuration of nucleophilic glycosyl donor and is independent from the structure of the carbohydrate chain, protective groups, and alcohol acceptors. This method, in combination with C-glycosylation, will address the critical challenges of oligosaccharides synthesis and can be incorporated into automated and high-throughput synthesis. Given the generality and a predictable nature of the glycosylation step, this new technology can be used by researchers with minimal training in organic synthesis, and the discoveries of this study can have important impact on the development of new diagnostic tools and therapies.

项目概要/摘要 碳水化合物（也称为糖类或聚糖）在生物分子中占据着核心作用，因为 它们参与生物学中的许多信号传导和识别过程。而且， 碳水化合物是许多疫苗、抗糖尿病和抗病毒疫苗的重要结构成分 药物和抗肿瘤候选药物。尽管化学糖基化方法取得了重大进展， 提供精确控制糖苷键异头构型的通用技术是 要求。在本提案中，我们的目标是开发有效且实用的合成方法和策略 生物活性寡糖。在目标 1 中，我们将扩展亲核糖基供体的工具集。瞄准 2、开发并应用氧化糖基化方法制备低聚糖 定义的异头构型。这种新颖的方法将建立一个稳健的协议， 异头键的构型在亲核糖基供体的构型中预先定义，并且 独立于碳水化合物链、保护基团和醇受体的结构。 该方法与 C-糖基化相结合，将解决寡糖的关键挑战 合成并可纳入自动化和高通量合成中。鉴于一般性 以及糖基化步骤的可预测性，这项新技术可供研究人员使用 有机合成方面的培训最少，这项研究的发现可以对有机合成产生重要影响 开发新的诊断工具和疗法。