Methods and Mechanisms in Carbohydrate Chemistry

虽然糖化学在过去的二十年里有了长足的发展， 复合寡糖或糖缀合物的合成仍然是非常困难的 具有挑战性，但至关重要的任务。这种合成中固有的困难 由于许多原因，这些原因集中在化学的复杂性上， 与寡核苷酸和肽合成相比。最重要的 任何寡糖合成中的反应是糖苷键的形成， 为此目的存在绝对压倒性的方法。 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，由于对机制的详细了解很少， 一点普遍性。 这项建议的基本主题是， 复杂的寡糖合成最好是通过提高对 糖苷键形成的机制，再加上更多的发展， 高效、直接和通用的基于机制的方法。一个必要步骤 为了达到这一目标，详细研究了糖基化的机制 因此，本建议涉及若干被认为至关重要的问题 解决这个问题的关键要解决的问题包括：i）发展 阳离子时钟法测定唾液酸反应动力学， 呋喃糖苷糖苷键的形成。㈡确定各方的相互作用 链构象和保护基的变化及其对 糖基化立体选择性。（三）制定有效的方法 微生物唾液酸、军团菌胺酸和假氨基酸的合成，以及 他们的Glycosides iv）开发用于合成C5改性的 唾液酸通过立体控制的取代脱氨基作用。

Although glycochemistry has developed in leaps and bounds in the last two decades, 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 i) the development of cation clock methods for the determination of reaction kinetics in sialic acid and furanoside glycosidic bond formation. ii) The determination of the interplay of the side chain conformation and of protecting groups and their combined influence on glycosylation stereoselectivity. iii) The development of methods for the efficient synthesis of the microbial sialic acids, legionaminic acid and pseudaminic acid, and of their glycosides. iv) The development of novel methods for the synthesis of C5 modified sialic acids by stereocontrolled substitutive deamination.