De Novo Synthesis of Oligosaccharides

项目摘要 本次提案更新的总体目标是继续开发一个高效、通用的 寡糖（X = O）的不对称合成策略，并将其扩展到合成 类似的低聚环醇（X = CH 2，方案1）。我们提出的方法有可能彻底改变 低聚糖的合成方式。我们的方法围绕着使用高度立体选择性的 钯催化的糖基化（X = O：2.1 <$/2.4 <$to 2.2 <$/2.5 <$）和环化（X = CH 2;方案1）。 有一个惊人的研究量直接对寡糖的合成; 然而，当涉及非天然寡糖时，现有技术缺乏。这一缺陷是 这无疑是由于碳水化合物起始原料（葡萄糖、甘露糖和半乳糖）的数量有限。 一种补充办法是从大大简化的结构开始， 将其立体化学和功能复杂性增加到一系列结构（例如，1.5/1.6至1.1-1.3;方案 1）。指导我们的合成方法的基本假设是相信有许多碳水化合物 类似物，由于合成的限制，它们仍未被发现。因此，我们认为， 允许单糖（即未充分官能化的）容易地结合到寡糖基序中 极大地使发现具有广泛功能的新结构成为可能。

Project Summary The overall objective of this proposal renewal is to continue our development of an efficient and general strategy for the asymmetric synthesis of oligosaccharides (X = O) and to expand it to the synthesis of analogous oligo-cyclitols (X = CH2, Scheme 1). The method we propose has the potential to revolutionize the way oligosaccharides are synthesized. Our method revolves around the use of a highly stereoselective palladium catalyzed glycosylation (X = O: 2.1¿/2.4¿ to 2.2 ¿/2.5¿) and cyclitolization (X = CH2; Scheme 1). There has been an astounding amount of research directed toward the synthesis of oligosaccharides; however, when it comes to unnatural oligosaccharides, the current state of the art is lacking. This deficiency is undoubtedly due to the limited number of carbohydrate starting materials (glucose, mannose, and galactose). A complementary approach would be to start with a significantly simplified structure and to sequentially increase its stereochemical and functional complexity to a range of structures (eg., 1.5/1.6 to 1.1-1.3; Scheme 1). The underlying hypothesis that guides our synthetic approach is the belief that there are many carbohydrate analogs, which remain undiscovered because of synthetic limitations. Thus, we believe a methodology that allows for the facile incorporation of simple sugars (i.e. under-functionalized) into oligosaccharide motifs will drastically enable the discovery of new structures with a wide range of functions.