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的生物过程中以及在人类疾病的诊断和治疗中扮演着重要的角色。获取寡糖和糖共轭化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，单糖聚合成各种不同的立体和区域异构体结构。因此，控制化学糖苷反应的立体选择性和区域选择性是最重要的。然而，在大量其他羟基存在的情况下，一个羟基的选择性官能化构成了一个重大的化学挑战，而且大多数低聚糖的合成必须依赖于复杂而冗长的保护基团策略来促进仅在所需位置的反应。这项建议中描述的研究重点是开发能够同时控制糖苷反应的立体化学和区域化学的小分子催化剂。研究方法包括合理设计氢键供体催化剂，部分受到自然界中发现的蛋白质-碳水化合物相互作用的指导。最先进的合成、机械和理论工具将促进对这些催化剂的系统评估和优化，以实现控制不同碳水化合物羟基的相对反应活性的目标。这项拟议研究的成功发展有望改变低聚糖的合成，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，在实现这一目标的过程中揭示的基本机理发现有望大大有助于我们对碳水化合物分子识别的理解，并为更多不同的位置选择性官能化反应的催化方法奠定基础。

 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.