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1. Bismuth( iii ) triflate as a novel and efficient activator for glycosyl halides

   https://doi.org/10.1039/D1OB00093D  

   Steber, Hayley B.; Singh, Yashapal; Demchenko, Alexei V. (April 2021, Organic & Biomolecular Chemistry)

   null (Ed.)

   Presented herein is the discovery that bismuth( iii ) trifluoromethanesulfonate (Bi(OTf) 3 ) is an effective catalyst for the activation of glycosyl bromides and glycosyl chlorides. The key objective for the development of this methodology is to employ only one promoter in the lowest possible amount and to avoid using any additive/co-catalyst/acid scavenger except molecular sieves. Bi(OTf) 3 works well in promoting the glycosidation of differentially protected glucosyl, galactosyl, and mannosyl halides with many classes of glycosyl acceptors. Most reactions complete within 1 h in the presence of only 35% of green and light-stable Bi(OTf) 3 catalyst. 

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2. Palladium( ii )-assisted activation of thioglycosides

   https://doi.org/10.1039/D1OB00004G  

   Escopy, Samira; Singh, Yashapal; Demchenko, Alexei V. (March 2021, Organic & Biomolecular Chemistry)

   null (Ed.)

   Described herein is the first example of glycosidation of thioglycosides in the presence of palladium( ii ) bromide. While the activation with PdBr 2 alone was proven feasible, higher yields and cleaner reactions were achieved when these glycosylations were performed in the presence of propargyl bromide as an additive. Preliminary mechanistic studies suggest that propargyl bromide assists the reaction by creating an ionizing complex, which accelerates the leaving group departure. A variety of thioglycoside donors in reactions with different glycosyl acceptors were investigated to determine the initial scope of this new reaction. Selective and chemoselective activation of thioglycosides over other leaving groups has also been explored. 

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3. Direct, stereoselective thioglycosylation enabled by an organophotoredox radical strategy

   https://doi.org/10.1039/D0SC04136J  

   Ji, Peng; Zhang, Yueteng; Gao, Feng; Bi, Fangchao; Wang, Wei (December 2020, Chemical Science)

   null (Ed.)

   While strategies involving a 2e − transfer pathway have dictated glycosylation development, the direct glycosylation of readily accessible glycosyl donors as radical precursors is particularly appealing because of high radical anomeric selectivity and atom- and step-economy. However, the development of the radical process has been challenging owing to notorious competing reduction, elimination and/or S N side reactions of commonly used, labile glycosyl donors. Here we introduce an organophotocatalytic strategy through which glycosyl bromides can be efficiently converted into corresponding anomeric radicals by photoredox mediated HAT catalysis without a transition metal or a directing group and achieve highly anomeric selectivity. The power of this platform has been demonstrated by the mild reaction conditions enabling the synthesis of challenging α-1,2- cis -thioglycosides, the tolerance of various functional groups and the broad substrate scope for both common pentoses and hexoses. Furthermore, this general approach is compatible with both sp 2 and sp 3 sulfur electrophiles and late-stage glycodiversification for a total of 50 substrates probed. 

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4. Chapter Seven - High-throughput screening of glycosynthases using azido sugars for oligosaccharides synthesis

   Kumar, Mohit; Bandi, Chandra_Kanth; Chundawat, Shishir PS (January 2023, Methods in enzymology)

   Shukla, Arun K (Ed.)

   Glycosynthases are mutant glycosyl hydrolases that can synthesize glycosidic bonds between acceptor glycone/aglycone groups and activated donor sugars with suitable leaving groups (e.g., azido, fluoro). However, it has been challenging to rapidly detect glycosynthase reaction products involving azido sugars as donor sugars. This has limited our ability to apply rational engineering and directed evolution methods to rapidly screen for improved glycosynthases that are capable of synthesizing bespoke glycans. Here, we outline our recently developed screening methodologies for rapidly detecting glycosynthase activity using a model fucosynthase enzyme engineered to be active on fucosyl azide as donor sugar. We created a diverse library of fucosynthase mutants using semi-random and random error prone mutagenesis and then identified improved fucosynthase mutants with desired activity using two distinct screening methods developed by our group to detect glycosynthase activity (i.e., by detecting azide formed upon completion of fucosynthase reaction); (a) pCyn-GFP regulon method, and (b) Click chemistry method. Finally, we provide some proof-of-concept results illustrating the utility of both these screening methods to rapidly detect products of glycosynthase reactions involving azido sugars as donor groups. 

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5. Catalytic Orthogonal Glycosylation Enabled by Enynal‐Derived Copper Carbenes

   https://doi.org/10.1002/adsc.202301207  

   Pratap_Singh, Surya; Ghosh, Bidhan; Sharma, Indrajeet (March 2024, Advanced Synthesis & Catalysis)

   Abstract Herein, we present an approach for catalytic orthogonal glycosylation utilizing earth‐abundant copper carbenes. This method operates under mild conditions and employs readily accessible starting materials, including benchtop stable enynal‐derived glycosyl donors, synthesized at the gram scale. The reaction accommodates a variety of glycosyl acceptors, including primary, secondary, and tertiary alcohols. The enynal‐derived copper carbenes exhibit remarkable reactivity and selectivity, allowing for the formation of glycosidic linkages with different protecting groups and stereochemical patterns. This approach provides access to both 1,2‐cis‐ and ‐trans‐glycosidic linkages. The product stereoselectivity is independent of the anomeric configuration of the glycosyl donor, which also has orthogonal reactivity to widely used alkynes and thioglycoside donors. An iterative synthesis of a trisaccharide further demonstrates the application of this orthogonal reactivity. 

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