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

未保护和未活化碳水化合物的立体选择性多组分反应。

基本信息

批准号：
265673199
负责人：
Professor Dr. Rainer Mahrwald
金额：
--
依托单位：
Institut für Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/265673199?language=en
关键词：
Stereoselective multicomponent reactions unprotected unactivated

项目摘要

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.

该项目旨在系统地研究和扩大操作简单和高度选择性地获得糖基化的人造多肽的初步结果。在初步工作中，我们为这种无保护碳水化合物和氨基酸的高选择性多组分反应的进一步广泛应用奠定了基础。建立了以下化学选择性和立体选择性的暂定规则。所部署的碳水化合物的构型决定了二酮基哌嗪或内酯的形成。核糖和脯氨酸与异氰酸乙酯反应，只生成内酯。当在相同条件下与阿拉伯糖一起使用时，只检测到2.6-二酮基哌嗪。所部署的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，观察到高度选择性的C-C键的形成，而当使用D-Pro时，只观察到反构型的产物。在与羟化氨基酸(丝氨酸或苏氨酸)的反应中，观察到亚胺酸酯的形成。这代表了所部署的碳水化合物的不同寻常的链延长。通过这种转化，似乎可以很容易地获得亚胺碳水化合物。立体和化学选择性的结果将得到更深入和广泛的研究。这种简单而有效的反应的普遍应用应该通过进一步扩大底物范围来证明，例如氨基酸、碳水化合物和异氰化物。在这种转化中将测试几种二糖或三糖(一般为低聚糖)。该项目的目的是通过无保护碳水化合物和氨基酸的这种直接多组分反应来简化和推广现有的C-糖基化人造多肽的合成。从而为复杂糖基化多肽的全合成开辟了新的途径。