Synthesis of Heterocycle-Linked C-Glycosyla-Amino Acids and C-Glycopeptides

摘要

Non-natural C-glycosyl a-amino acids are building-blocks forthe co-translational modification of natural glycopeptides.These are key components of the complex machinery thatoperates in vital processes of all living organisms, rangingfrom eubacteria to eukaryotes. While a wide range of C-glycosyl amino acids have been synthesized, we have designedand prepared a small collection of a new class of these aminoacids whose structure features a heterocycle ring holding thecarbohydrate and the amino acid fragments. Isoxazole,triazole, tetrazole, and pyridine moieties were used as suitablelinkers in this project owing to their easy construction viaHuisgen cycloaddition and Hantzsch multicomponent reaction.Details on the synthesis of each family of these glycol-conjugates are given below, some emphasis being given to theefficiency and generality of each method employed. Thepotential of these glycosyl amino acids in non-naturalglycopeptide synthesis is exemplified by the coupling of apyridine-linked derivative with two natural amino acids to givea non-natural glycotripeptide.