Catalyst-Controlled Stereo- and Regioselective Glycosidation Reactions

催化剂控制的立体和区域选择性糖苷化反应

• 批准号: 9051354
• 负责人: Alison Wendlandt
• 金额: $ 5.25万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9051354
• 关键词: Amino Acids; Area; Biological Process; Biological Response Modifier Therapy; Carbohydrates; Chemicals; Complex; Covalent Interaction; Development; Diagnosis; Evaluation; Family; Glycobiology; Glycoconjugates; Goals; Hydrogen Bonding; Inflammation; Libraries; Methods; Modeling; Modification; Monosaccharides; Nature; Nucleotides; Oligosaccharides; Play; Polymers; Positioning Attribute; Protein-Carbohydrate Interaction; Reaction; Research; Resources; Role; Route; Site; Structure; Testing; Thiourea; Time; Virus Diseases; Work; biological systems; cancer therapy; catalyst; chemical synthesis; computerized tools; covalent bond; design; human disease; hydroxyl group; improved; molecular recognition; public health relevance; small molecule; stereochemistry; therapeutic target; tool

 DESCRIPTION (provided by applicant): Carbohydrates play an important role in many fundamental biological processes, as well as in the diagnosis and treatment of human disease. Efficient chemical methods for accessing oligosaccharides and glycoconjugates are crucial for continued progress in the field of glycobiology. Unlike amino acids and nucleotides, which form linear polymers, monosaccharides polymerize into a variety of different stereo- and regioisomeric structures. Control over the stereo- and regioselectivity of chemical glycosidation reactions is, therefore, paramount. However, the selective functionalization of one hydroxyl group in the presence of numerous others poses a significant chemical challenge, and most oligosaccharide syntheses must rely upon elaborate and lengthy protecting group strategies to promote reaction at only the desired site. The research described in this proposal focuses on the development of small-molecule catalysts capable of controlling both the stereochemistry and the regiochemistry of glycosidation reactions. The research approach involves the rational design of hydrogen-bond donor catalysts guided, in part, by protein-carbohydrate interactions found in nature. State-of-the-art synthetic, mechanistic and theoretical tools will facilitate the systematic evaluation and optimization of these catalysts towards the goal of controlling the relative reactivity of different carbohydrate hydroxyl groups. The successful development of this proposed research is anticipated to transform oligosaccharide synthesis, dramatically reducing the time and resources necessary to chemically synthesize complex carbohydrates. Further, fundamental mechanistic findings revealed en route to this goal are anticipated to contribute significantly to our understanding of carbohydrate molecular recognition and to lay the groundwork for catalytic approaches to more diverse site-selective functionalization reactions.

 描述（由适用提供）：碳水化合物在许多基本生物过程以及人类疾病的诊断和治疗中起着重要作用。用于获取寡糖和糖缀合物的有效化学方法对于糖生物学领域的持续进展至关重要。与形成线性聚合物形成线性聚合物的氨基酸和核苷酸不同，单糖聚合成各种不同的立体异构体结构。因此，控制化学糖化反应的立体和调节受体至关重要。但是，在存在许多其他羟基的情况下，一个羟基的选择性功能化构成了重大的化学挑战，并且大多数寡糖合成必须依赖于详尽而冗长的保护群策略，以仅在所需部位促进反应。该提案中描述的研究重点是能够控制立体化学和糖化反应的区域化学的小分子催化剂的发展。研究方法涉及氢键供体催化剂的合理设计，部分地是由自然界中的蛋白质 - 碳水化合物相互作用引导的。最先进的合成，机械和理论工具将促进这些催化剂的系统评估和优化，以控制不同碳水化合物羟基的相对反应性。预计这项拟议的研究的成功发展将改变寡糖的合成，从而大大减少化学合成复杂碳氢化物所需的时间和资源。此外，预计在实现这一目标的途径的基本机理发现将显着有助于我们对碳氢化物分子识别的理解，并为催化方法奠定基础，以实现更长的站点选择性功能反应。