Methods and Mechanisms in Carbohydrate Chemistry

描述（由申请人提供）：虽然糖化学在过去十年左右已经有了飞跃式的发展，但复杂寡糖或糖缀合物的合成仍然是一项非常具有挑战性但至关重要的任务。这种合成中固有的困难是由于与寡核苷酸和肽合成相比集中在化学复杂性上的许多原因而出现的。任何寡糖合成中最重要的反应是糖苷键的形成，并且存在绝对压倒性数量的方法来实现这一目标。不幸的是，这些方法中的绝大多数都是根据经验开发的，因此对机理的详细了解很少，并且具有很小的通用性。 该提案的基本主题是，复杂寡糖合成的简化的挑战最好通过对糖苷键形成机制的更好理解来满足，再加上开发更有效，更直接和更通用的基于机制的方法。实现这一目标的一个必要步骤是糖基化机制的机制的详细调查，因此，这一建议解决了几个问题，认为这一问题的解决至关重要。要解决的问题包括糖基oxocarbenium离子的光谱鉴定和研究的方法的发展，基于NMR的动力学同位素效应方法的糖基化动力学研究的发展，基于质谱的方法的发展的影响的研究保护基团的oxocarbenium离子的稳定性，和改进的糖基化系统的发展基于这些研究的机制。

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.