Kupfer-katalysierte Azid-Alkin-Cycloaddition zur Modifikation von Kohlenhydraten
Copper-catalyzed azide-alkyne-cycloaddition for the modification of carbohydrates
by Pascal Fuchs
Date of Examination:2020-02-21
Date of issue:2020-02-26
Advisor:Prof. Dr. Kai Zhang
Referee:Prof. Dr. Kai Zhang
Referee:Prof. Dr. Thomas Heinze
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Abstract
English
The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most prominent representatives of click chemistry. Due to its facile procedure and high yields it has been growing in popularity since its discovery 17 years ago. The reaction can be performed in the presence of water and air, but catalyst systems such as copper(I)-iodide/N,N-diisopropylethylamine (DIPEA) also allow the reaction to be performed under inert atmosphere and moisture-free conditions. In carbohydrate chemistry, especially in cellulose chemistry, the application of this catalyst system is less investigated. One goal of this thesis was the synthesis of a cellulose derivative which can be converted through CuAAC with CuI/DIPEA as catalyst system in organic solvents. Subsequently, the successful CuI/DIPEA-catalyzed azide-alkyne cycloaddition was to be demonstrated using this cellulose derivative. This was accomplished by the development of a novel one-pot reaction which allows the efficient synthesis of 6-bromo-6-deoxy-2,3-tris(trimethylsilyl) cellulose, starting from microcrystalline cellulose (MCC). In the subsequent nucleophilic substitution of the bromide against azide groups the organosoluble 6-azido-6-deoxy-2,3-tris(trimethylsilyl) cellulose was obtained as starting material for the CuI/DIPEA-catalyzed azide-alkyne cycloaddition. The azide-functionalized cellulose derivative was dissolved in THF and successfully reacted via CuAAC with an aliphatic and an aromatic alkyne under moisture-free and oxygen-free conditions. It was thus demonstrated that cellulose can be converted with CuI/DIPEA as catalyst system in anhydrous organic solvents by means of CuAAC. This further expands the scope of possible click reactions on cellulose. Another goal of my work was the development of a method for the preparation of linear polymers from monosaccharide derivatives by CuI/DIPEA-catalyzed azide-alkyne cycloaddition. This also required the development of a suitable alkyne- and azide-functionalized monosaccharide derivative. Until now, the polymerization of bifunctional monosaccharide derivatives into linear polymers was not possible because the cyclic oligomerization of the monomers dominated as the main reaction. Therefore, minimizing cyclic by-products has been a major challenge. First, the bifunctional glucose derivative 2,3,6-tris-O-benzyl-4-O-propargyl-β-D-glucopyranosylazide was synthesized. In order to prevent the cyclization of this derivative during the CuAAC, starter molecules were used which contained either azide or alkyne groups. Chains growing from the starter molecules cannot cyclize due to the lack of a second reactive chain end. As a first starter molecule silica nanoparticles (SiNPs) were chosen. Azide-functionality was introduced to their surface with a previously synthesized azide-bearing silane linker. After the CuAAC was finished, the SiNPs, including the polysaccharide analogues bound to them, could be separated from the cyclic products in thereaction solution by centrifugation and were analyzed separately. The reaction conditions were optimized in order to obtain the lowest possible yield of cyclic compounds and the highest possible degree of polymerization on the surface of the SiNPs. This was achieved by slow and continuous addition of the monomer over a period of 24 hours, which minimized the effective monomer concentration during the reaction, increasing the yield of linear compounds by 97 %. However, the yield was still below 20 %. In the next step, this method was used to synthesize block copolymers by polymerizing the monomer on alkyne end-functionalized polyethylene glycol 2000. Here, with yields above 90 %, only linear polymers were obtained. This shows that the CuI/DIPEA catalyst system and the method developed here are suitable for the synthesis of linear polysaccharide analogues with soluble starter molecules but can only be recommended to a limited extent for the synthesis of polysaccharide analogues on surfaces. The results obtained here suggest that the CuI/DIPEA catalyst system is also applicable for the polymerization of other (saccharide-based) monomers, provided that they cannot form cyclic dimers and the polymerization is carried out with a readily soluble starter molecule.
Keywords: CuAAC; Polymer chemistry; Cellulose