Stereo- and regioselective glycosidation is still a great challenge in carbohydrate chemistry. Among the tremendous endeavors in this area, acid–base catalysis, available to O-glycosyl trichloroacetimidate activation, is of particular interest. It features an alternative glycosidation pathway initiated by the sequential binding between the catalyst and the glycosyl acceptor and then with the glycosyl donor. Through the formation of a catalyst–acceptor adduct, increased proton acidity and oxygen nucleophilicity are reached, thus enforcing donor activation and concomitant acceptor transfer. As the reaction takes place via an SN2-type transition state, essentially stereoselectivity is granted. Platinum­(IV) chloride is an ideal catalyst in this regard; it is a weak Lewis acid, yet it possesses high affinity to the glycosyl acceptor hydroxy group due to its ligand-binding capacity, thus affording from the α-configurated glycosyl donor the glycosidation product predominantly in β-configuration. In addition, the capacity of platinum­(IV) chloride to bidentate ligation is another advantage, as it enhances nucleophilicity differences between hydroxy groups, thus permitting regioselective glycosidation, as observed for various 1,2-cis-, 1,3-, and 1,2-trans-diol and 1,2,3-triol moieties present in carbohydrate acceptors. This observation found application in an efficient saponin natural product synthesis.

No abstract

Comprehensive Summary O‐Mannosylation plays a vital role in the regulation of a variety range of biological processes, for instance, brain and muscle development. However, the precise function remains largely unknown due to its innate heterogeneity. In this regard, it is still welcome to develop efficient methods to access diverse structurally‐defined glycopeptides. In this study, a diversity‐oriented assembly of O‐mannosyl α‐dystroglycan (α‐DG) glycopeptides has been achieved via a chemoenzymatic strategy. This strategy features (i) gram scale divergent synthesis of core m1, core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation; (ii) efficient glycopeptide assembly via the optimized microwave‐assisted solid phase peptide synthesis (SPPS); and (iii) enzymatic elaboration of the core glycan structures to install galactosyl and sialyl‐galactosyl moieties. The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1, core m2 and core m3 mannosyl glycans, including a core m2 glycopeptide bearing a heptasaccharide for the first time.

Comprehensive Summary Protein glycosylation is the most complex and diverse form of post‐translational modification in human body. Meanwhile, glycosylation of peptides and proteins emerges as a promising strategy to improve the pharmacokinetic profile of peptide‐ and protein‐based therapeutics. Owing to the importance of protein glycosylation, a rigorous evaluation of the relationship between the precise structure and biological function of glycoproteins has to be performed. Recently, chemical synthesis, chemoenzymatic synthesis and semisynthesis strategies have attracted extensive attentions towards the preparation of structurally defined glycopeptides and glycoproteins; the obtained synthetic glycoforms thus enable the thorough investigation of specific effects of protein glycosylation. This review highlights the recent progress in the development of novel strategies, preparation of homogeneous glycoproteins and exploration of structure‐activity relationships. On this basis, the challenges and prospects are discussed.