Stereoselective Synthesis of 2-Deoxy-α-N-Glycosides from Glycals with 1,4,2-Dioxazol-5-ones

The synthesis of N-glycosides has received significant attention due to their crucial role in carbohydrate chemistry.Despite considerable advancements developed in the construction of N-glycosides,methods for the stereoselective construction of 2-deoxy-α-N-glycosides are still limited.Herein,we disclosed a nickel-catalyzed hydroamination of glycals under mild conditions.This transformation could allow for the stereoselective synthesis of an array of 2-deoxy-α-N-glycosides with excellentα-stereoselectivity.Nickel-catalyzed glycosylation reactions,particularly those involving anomeric C(sp")-metal bond formation,have proven to be an effective and stereoselective strategy for producing various N-glycosides.Additionally,with highlight of the application of this reaction,y-sugar amino acidderivatives weresynthesized.

Palladium-Catalyzed One-Step Synthesis of Stereodefined Difunctionalized Glycals

Efficiently modifying glycals by directly introducing functional groups into their double bonds is a longstanding challenge.Here,the strategy of introducing two different functional groups into 1-iodoglycals to obtain modified glycals in one step through palladium catalysis was reported for the first time,and the modified glycals contained stereodefined tetrasubstituted olefins.Using this method,various difunctionalized glycals that were difficult to form by other routes were synthesized in moderate to good yields.Control experiments and density functional theory calculations show that the palladium catalyst played dual roles in this transformation,namely,inducing nucleophilic substitution and catalyzing Suzuki coupling.The reaction intermediate was isolated and confirmed by X-ray crystallographic analysis.Furthermore,the gram-scale synthesis and facile deprotection of the target compound enhances the practicality of this strategy.

Synthesis of 2-Deoxy-C-Glycosides via Iridium-Catalyzed sp^(2)and sp^(3)C-H Glycosylation with Unfunctionalized Glycals

A new protocol for the synthesis of 2-deoxy-C-aryl-glycosides and 2-deoxy-C-alkyl-glycosides via iridium-catalyzed directed C—H glycosylation with glycals is reported.The method is amenable for both the C_(2)C—H glycosylation of indoles and the methyl C—H glycosylation of secondary methyl amines under the control of an N-linked benzoxazole directing group.The benzoxazole group can be cleanly removed by the treatment of KOH or LiAlH_(4).

A Rapid Synthesis of Pyranoid Glycals Promoted by β-Cyclodextrin and Ultrasound

A convenient and environmentally benign procedure for the synthesis of glycals from glycosyl bromides with very low zinc dust loading （1.5 equiv.） is described. The process is activated by β-cyclodextrin and ultrasound. Based on 19 samples, this method has been demonstrated to be highly effective for a broad range of glycosyl bromides, including acidor base-sensitive and disaccharide glycosyl bromides. A yield of 85%--96% of glycals was obtained.

C-Aryl Glycosylation via Interrupted Pummerer Rearrangement

C-aryl glycosides are an important kind of carbohydrate derivatives for drug discovery,due to their distinctive attributes of resistance to hydrolysis from enzymes.Herein,C-aryl glycosylation was established for the synthesis of 2-sulfur C-aryl glycals and 1,2-dihydrobenzofuran-fused C-aryl glycosides via interrupted Pummerer process,featured with sulfonium-tethered[3,3]-sigmatropic rearrangement between sulfoxide glycals and phenols.This protocol offers a broad substrate scope with diverse glycosyl and phenols.Dapagliflozin,Empagliflozin,and Ipragliflozin analogs were straightforward achieved,respectively.

Chemical synthesis of a synthetically useful L-galactosaminuronic acid building block

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.

Improvement of Kdo’s efficient large-scale chemical synthesis method

Kdo residues are widely distributed in bacteria.They are components of bacterial lipopolysaccharide(LPS)and capsular polysaccharides,which can be recognized by the human adaptive immune system,and have great potential for developing new sugar chips and antibacterial vaccines.By improving the existing methods,we optimized the Kdo chemical synthesis method,which was able to efficiently synthesize Kdo monosaccharides with high purity,laying a foundation for the construction of subsequent compound libraries.Kdo acylation can easily form 1,5-lactones and reduce the efficiency of synthesis.By changing the synthesis sequence,we avoided the formation of Kdo 1,5-lactones,improved the synthesis efficiency of Kdo glycals,and provided a new strategy for derivatization.