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Abstract: A chemoenzymatic synthon was designed to expand the scope of the chemoenzymatic synthesis of carbohydrates. The synthon was enzymatically converted into carbohydrate analogues, which were readily derivatized chemically to produce the desired targets. The strategy is demonstrated for the synthesis of glycosides containing 7,9‐di‐N‐acetyllegionaminic acid (Leg5,7Ac2), a bacterial nonulosonic acid (NulO) analogue of sialic acid. A versatile library of α2‐3/6‐linked Leg5,7Ac2‐glycosides was built by using chemically synthesized 2,4‐diazido‐2,4,6‐trideoxymannose as a chemoenzymatic synthon for highly efficient one‐pot multienzyme (OPME) sialylation followed by downstream chemical conversion of the azido groups into acetamido groups. The syntheses required 10 steps from commercially available d‐fucose and had an overall yield of 34–52 %, thus representing a significant improvement over previous methods. Free Leg5,7Ac2 monosaccharide was also synthesized by a sialic acid aldolase‐catalyzed reaction. [ABSTRACT FROM AUTHOR]

A highly efficient chemoenzymatic method for synthesizing glycosphingolipids using α-Gal pentasaccharyl ceramide as an example is reported here. Enzymatic extension of the chemically synthesized lactosyl sphingosine using efficient sequential one-pot multienzyme (OPME) reactions allowed glycosylation to be carried out in aqueous solutions. Facile C18 cartridge-based quick (＜30 minutes) purification protocols were established using minimal amounts of green solvents (CH3CN and H2O). Simple acylation in the last step led to the formation of the target glycosyl ceramide in 4 steps with an overall yield of 57%. [ABSTRACT FROM AUTHOR]

Nitrosyl tetrafluoroborate (NOBF4) has been successfully applied as an efficient organocatalyst for the preparation of 2,3- unsaturated and 2-deoxyglycosides of hindered alcohols, aryl thiols, and aryl sulfonamides from glycal derivatives under the Ferrier rearrangement conditions. Product yields and stereo-outcomes were very good. [ABSTRACT FROM AUTHOR]

We report here an efficient, fast, and cost-effective strategy for synthesizing pseudoglycals by the reaction of glycals with alcohols or nucleophiles using zinc tetrafluoroborate. This mild, transition metal-free approach allowed the α-selective synthesis of pseudoglycals using a wide range of acceptors containing various protecting groups/functionalities. This method is exemplified by the synthesis of digitoxin α-L-amicetose, a known potential cardiac glycoside anticancer agent. The improved 3-step synthesis from L-rhamnal afforded an overall yield of 54%, thus representing a significant improvement over the previous method.

Efficient stereo- and regioselective O-glycosylation methods remain essential to capacitate the studies of sugars and sugar derivatives in various disciplines. In this work, we demonstrated an operationally simple and cost-effective strategy for the synthesis of 1,2-trans glycosides by the activation of armed O-glycosyl trichloroacetimidates donor using zinc tetrafluoroborate. This mild, transition metal-free, and scalable approach allowed stereo- and regioselective synthesis of β-glycosides with a wide range of acceptors containing various protecting groups/functionalities. This method is exemplified by synthesizing a branched trisaccharide fragment related to the cell wall O-polysaccharide of E. Coli O27., (© 2024 Wiley-VCH GmbH.)

Streptococcus gordonii is a Gram-positive bacterial species that typically colonizes the human oral cavity, but can also cause local or systemic diseases. Serine-rich repeat (SRR) glycoproteins exposed on the S. gordonii bacterial surface bind to sialylated glycans on human salivary, plasma, and platelet glycoproteins, which may contribute to oral colonization as well as endocardial infections. Despite a conserved overall domain organization of SRR adhesins, the Siglec-like binding regions (SLBRs) are highly variable, affecting the recognition of a wide range of sialoglycans. SLBR-N from the SRR glycoprotein of S. gordonii UB10712 possesses the remarkable ability to recognize complex core 2 O -glycans. We here employed a multidisciplinary approach, including flow cytometry, native mass spectrometry, isothermal titration calorimetry, NMR spectroscopy from both protein and ligand perspectives, and computational methods, to investigate the ligand specificity and binding preferences of SLBR-N when interacting with mono- and disialylated core 2 O -glycans. We determined the means by which SLBR-N preferentially binds branched α2,3-disialylated core 2 O -glycans: a selected conformation of the 3'SLn branch is accommodated into the main binding site, driving the sTa branch to further interact with the protein. At the same time, SLBR-N assumes an open conformation of the CD loop of the glycan-binding pocket, allowing one to accommodate the entire complex core 2 O -glycan. These findings establish the basis for the generation of novel tools for the detection of specific complex O -glycan structures and pave the way for the design and development of potential therapeutics against streptococcal infections., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A chemoenzymatic synthon was designed to expand the scope of the chemoenzymatic synthesis of carbohydrates. The synthon was enzymatically converted into carbohydrate analogues, which were readily derivatized chemically to produce the desired targets. The strategy is demonstrated for the synthesis of glycosides containing 7,9-di-N-acetyllegionaminic acid (Leg5,7Ac 2 ), a bacterial nonulosonic acid (NulO) analogue of sialic acid. A versatile library of α2-3/6-linked Leg5,7Ac 2 -glycosides was built by using chemically synthesized 2,4-diazido-2,4,6-trideoxymannose as a chemoenzymatic synthon for highly efficient one-pot multienzyme (OPME) sialylation followed by downstream chemical conversion of the azido groups into acetamido groups. The syntheses required 10 steps from commercially available d-fucose and had an overall yield of 34-52 %, thus representing a significant improvement over previous methods. Free Leg5,7Ac 2 monosaccharide was also synthesized by a sialic acid aldolase-catalyzed reaction., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)