Catalyst-Controlled Stereo- and Regioselective Glycosidation Reactions

 描述（由申请人提供）：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。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。与形成线性聚合物的氨基酸和核苷酸不同，单糖可以形成各种不同的立体异构体和区域异构体结构。因此，控制化学糖苷化反应的立体选择性和区域选择性至关重要。然而，一个羟基在许多其他羟基的存在下的选择性官能化提出了重大的化学挑战，大多数寡糖合成必须依赖于精心设计和冗长的保护基团策略，以促进仅在所需位点的反应。本提案中描述的研究重点是能够控制糖苷化反应的立体化学和区域化学的小分子催化剂的开发。研究方法涉及氢键供体催化剂的合理设计，部分由自然界中发现的蛋白质-碳水化合物相互作用指导。国家的最先进的合成，机械和理论工具将有助于系统的评估和优化这些催化剂的目标是控制不同的碳水化合物羟基的相对反应性。这项拟议研究的成功开发预计将改变寡糖合成，大大减少化学合成复杂碳水化合物所需的时间和资源。此外，基本的机制研究结果显示，在通往这一目标的道路上，预计将大大有助于我们的理解碳水化合物分子识别，并奠定基础的催化方法，更多样化的位点选择性功能化反应。

 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.