Stereoselective multicomponent reactions of unprotected and unactivated carbohydrates. A direct access to glycosylated peptidomimetics

该项目旨在系统地研究和扩展操作简单和高选择性获得糖基化人工肽的初步结果。在初步工作中，我们已经建立了基础，进一步普遍应用这种高度选择性的多组分反应的未保护的碳水化合物和氨基酸。已经建立了以下化学选择性和立体选择性的暂定规则。所配置的碳水化合物的构型决定了二酮哌嗪或内酯的形成。在核糖和脯氨酸与异氰乙酸酯的反应中，仅形成内酯。当在相同条件下与阿拉伯糖一起使用时，仅检测到2.6-二酮哌嗪。氨基酸的构型决定了这些反应的构型结果。在与L-脯氨酸的反应中，观察到高度顺式选择性的C-C键形成，而当使用D-脯氨酸时，仅观察到反构型产物。在与羟基化氨基酸（丝氨酸或苏氨酸）的反应中，观察到亚氨酸酯的形成。这代表了展开的碳水化合物的不寻常的链伸长。通过这种转化，似乎可以容易地获得亚氨基碳水化合物。立体以及化学选择性的结果将进行更深入的研究和推广。这种简单而有效的反应的一般应用应通过进一步扩大底物范围如氨基酸、碳水化合物和异腈来证明。在该转化中将检测几种二糖或三糖（通常为寡糖）。本项目的目的是简化和推广现有的C-糖基化，人工肽的合成，通过这种直接的多组分反应的未保护的碳水化合物和氨基酸。从而为复杂糖基化肽的全合成开辟了一条新的途径。

This project aims to investigate systematically and expand first results of an operationally simple and highly selective access to glycosylated, artificial peptides. In preliminary works we have established the foundation for a further general application of this highly selective multicomponent reaction of unprotected carbohydrates and amino acids. The following tentative rules of chemoselectivity and stereoselectivity have been established. The configuration of the carbohydrates deployed dictates the formation of diketopiperazines or lactones. In reaction of ribose and proline with isocyanoacetate solely lactones were formed. When used with arabinose under the same conditions exclusively 2.6-diketopiperazines were detected. The configuration of amino acids deployed dictates the configurative outcome of these reactions. In reaction with L-proline a highly syn-selective C-C bond formation is observed, whereas when using D-proline anti-configured products were observed exclusively. In reactions with hydroxylated amino acids (serine or threonine) the formation of imidoesters was observed. This represents an unusual chain elongation of the deployed carbohydrates. By means of this transformation an easy access to iminocarbohydrates appears obtainable. Stereo- as well as chemoselective results will be investigated more deeply and generalized. The general application of this simple and efficient reaction should be demonstrated by a further broadening of substrate scope such as amino acids, carbohydrates and isocyanides. Several di- or trisaccharides will be tested in this transformation (in general oligosaccharides). The aim of this project is to simplify and to generalize the existing syntheses of C-glycosylated, artificial peptides by means of this direct multicomponent reaction of unprotected carbohydrates and amino acids. Thus, a new access is opened up for the total syntheses of complicated glycosylated peptides.