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

• Applicant: Professor Dr. Rainer Mahrwald
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Biological and Biomimetic Chemistry
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 265673199

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.

• DFG Programme: Research Grants