Department of Chemistry, Yale University, New Haven, CT, USA.
Nat Chem. 2018 Jun;10(6):644-652. doi: 10.1038/s41557-018-0041-8. Epub 2018 Apr 30.
Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides. The transformation, which uses glycosyl fluoride donors and is promoted by Ca(OH), proceeds rapidly at room temperature in water, with good yields and selective formation of unique anomeric products depending on the stereochemistry of the glycosyl donor. High functional group tolerance is observed, and the phenol glycosylation occurs selectively in the presence of virtually all side chains of the proteinogenic amino acids with the singular exception of Cys. This method offers a highly selective, efficient, and operationally simple approach for the protecting-group-free synthesis of O-aryl glycosides and Tyr-O-glycosylated peptides in water.
糖基化天然产物和合成糖肽是生物化学探针和治疗剂的重要且不断增长的来源。然而，能够在不使用保护基团的情况下在肽中实现内源性氨基酸功能的水性糖基化的方法却很少。在这里，我们报告了一种转化方法，该方法可以促进广泛的小分子、未保护的酪氨酸以及一系列复杂的、完全未保护的肽中酪氨酸残基中酚官能团的高效水性 O-糖基化。该转化使用糖基氟化物供体，并在 Ca(OH)2 的促进下，在室温下在水中迅速进行，具有良好的产率和根据糖基供体的立体化学选择性形成独特的端基产物。观察到高官能团耐受性，并且酚基糖苷化在实际上所有的蛋白质氨基酸的侧链存在下选择性地发生，除了 Cys。该方法提供了一种高度选择性、高效且操作简单的方法，可在水中无保护基合成 O-芳基糖苷和 Tyr-O-糖基化肽。
