Diversity-Oriented Assembly of C-Glycosides via Late-Stage C−H Glycosylation

von Jun Wu
Dissertation
Datum der mündl. Prüfung:2023-07-26
Erschienen:2023-08-29
Betreuer:Prof. Dr. Lutz Ackermann
Gutachter:Prof. Dr. Manuel Alcarazo
Gutachter:Prof. Dr. Konrad Koszinowski
Gutachter:Prof. Dr. Dr. Lutz Tietze
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10072

 

 

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C-glycosides are widely distributed structural motifs found in natural products and commercially available drug molecules. Due to the stability of glycosidic C-C bonds against chemical and enzymatic hydrolysis, only C-glycosides have been used and synthesized as synthetic substitutes for O-glycosides. Research into the development of stereoselective C-glycosylation for accessing carbohydrate analogs has gained significant importance. However, the precise construction of glycosidic C-C bonds has long been a major challenge in the stereocontrolled synthesis of carbohydrates. In recent years, transition metal-catalyzed glycosylation reactions have established themselves for the synthesis of various C-glycosides and glycoconjugates due to their versatility, efficiency, and stereoselectivity. Nevertheless, the laborious synthesis of glycosyl donors and the need for toxic and sensitive organometallic reagents limit the broad applicability of these reactions. Hence, late-stage C-H glycosylation was developed. Initially, a palladium-catalyzed C(sp3)-H glycosylation of amino acids using triazole as an isostere for peptides was established. This allowed for the versatile synthesis of glycoamino acids, glycopeptides, and BODIPY-labeled glycoamino acids. Furthermore, a conceptually new C-glycosyl acceptor was designed through palladium-catalyzed C-H activation of glycosides. Equipped with glycal iodide donors, the selective palladium-catalyzed C-H glycosylation of glycosides was explored for the efficient assembly of oligosaccharides. Additionally, the method for the selective C(sp2)-H glycosylation of arenes using a stable glycosyl bromide donor via ruthenium catalysis was developed. Remarkably, the remote meta-C(sp2)-H glycosylation enabled the efficient construction of biologically important meta-C-aryl glycosides. Furthermore, a domino reaction for the construction of meta-C-alkyl glycosides in a single catalytic reaction with readily available starting materials was developed. Finally, the rhodium-catalyzed position-selective tryptophan peptide C7 amidation was achieved using easily accessible dioxazolones.
Keywords: C-H Glycosylation
 
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