Methods and Mechanisms in Carbohydrate Chemistry

描述(申请人提供)：尽管糖化学在过去十年左右取得了突飞猛进的发展，但合成复杂的寡糖或糖共轭化合物仍然是一个非常具有挑战性的任务，尽管这是非常重要的任务。与寡核苷酸和多肽合成相比，化学合成的复杂性是这种合成固有困难的原因之一。在任何低聚糖的合成中，最重要的反应是糖苷键的形成，为此存在着绝对压倒性的方法。不幸的是，这些方法中的绝大多数都是经验性开发的，因此对机理的详细了解很少，也没有什么普遍性。这一建议的基本主题是，简化复杂低聚糖合成的挑战最好通过改善对糖苷键形成机制的理解，以及开发更有效、更直接和更一般的基于机制的方法来实现。迈向这一目标的一个必要步骤是详细研究糖基化机制的机制，因此，这项建议解决了被认为对解决这一问题至关重要的几个问题。要解决的问题包括开发糖基氧碳正离子的光谱鉴定和研究方法，开发基于核磁共振的动力学同位素效应方法来研究糖基化动力学，开发基于质谱学的方法来研究保护基对氧碳正离子稳定性的影响，以及在这些机理研究的基础上开发改进的糖基化系统。

DESCRIPTION (provided by applicant): Although glycochemistry has developed in leaps and bounds in the last decade or so, the synthesis of a complex oligosaccharide or of a glycoconjugate remains a very challenging albeit critically important task. The difficulties inherent in such syntheses arise because of numerous reasons that center on the complexity of the chemistry when compared to that of oligonucleotide and peptide synthesis. The most important reactions in any oligosaccharide synthesis are the formation of the glycosidic bonds and there exists an absolutely overwhelming number of methods toward this end. Unfortunately the vast majority of these methods have been developed empirically, are therefore underpinned by very little detailed understanding of mechanism, and have very little generality. The underlying theme of this proposal is that the challenge of the simplification of complex oligosaccharide synthesis is best met by an improved understanding of the mechanisms of glycosidic bond formation, coupled with the development of more efficient, straightforward and general mechanism-based methods. A necessary step toward this goal is the detailed investigation of the mechanisms of glycosylation mechanisms, and accordingly this proposal addresses several issues considered critical to the resolution of this problem. The issues to be addressed include the development of methods for the spectroscopic identification and study of glycosyl oxocarbenium ions, the development of NMR-based kinetic isotope effect methods for the study of glycosylation kinetics, the development of mass spectrometry-based methods for the study of the influence of protecting groups on oxocarbenium ion stability, and the development of improved glycosylation systems based these studies of mechanism.