1-(2'-Hydroxy-2'-Methylpropionyl)Glycoside as a Versatile Glycosyl Donor for O-/C-Glycosylation.

Herein, we developed a Lewis acid-mediated O-glycosylation and C-glycosylation protocol using stable glycosyl 2'-hydroxy-2'-methylpropionates as donors. These glycosylation reactions reached completion within 1 h at room temperature. The practicality of this protocol is characterized by their straightforward operation and efficient applicability to various substrates, including both disarmed and armed glycosyl donors, through the remote activation of easily accessible TMSOTf.

Photosensitizer-free visible-light-promoted glycosylation enabled by 2-glycosyloxy tropone donors.

Photochemical glycosylation has attracted considerable attention in carbohydrate chemistry. However, to the best of our knowledge, visible-light-promoted glycosylation via photoactive glycosyl donor has not been reported. In the study, we report a photosensitizer-free visible-light-mediated glycosylation approach using a photoactive 2-glycosyloxy tropone as the donor.

Urea-catalyzed N-Glycosylation of Amides/Azacycles with Glycosyl Halides.

The efficient synthesis of N-glycosides via direct N-glycosylation of amides/azacycles has been reported. The glycosylation of amides/azacycles with glycosyl halides in the presence of a catalytic amount of urea proceeded smoothly to provide the corresponding N-glycosylated amides or nucleosides in good to excellent yields with 1,2-trans-stereoselectivity. Moreover, by the addition of terpyridine, the 1,2-cis-stereoselectivity was achieved.

Drug Discovery Based on Fluorine-Containing Glycomimetics.

Glycomimetics, which are synthetic molecules designed to mimic the structures and functions of natural carbohydrates, have been developed to overcome the limitations associated with natural carbohydrates. The fluorination of carbohydrates has emerged as a promising solution to dramatically enhance the metabolic stability, bioavailability, and protein-binding affinity of natural carbohydrates. In this review, the fluorination methods used to prepare the fluorinated carbohydrates, the effects of fluorination on the physical, chemical, and biological characteristics of natural sugars, and the biological activities of fluorinated sugars are presented.

Cancer Vaccines Based on Fluorine-Modified KH-1 Elicit Robust Immune Response.

KH-1 is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target of antitumor vaccines for cancer immunotherapies. However, most TACAs are thymus-independent antigens (TD-Ag), and they tend to induce immunological tolerance, leading to their low immunogenicity. To overcome these problems, some fluorinated derivatives of the KH-1 antigen were designed, synthesized, and conjugated to the carrier protein CRM197 to form glycoconjugates, which were used for immunological studies with Freund's adjuvant.

Iterative Synthesis of 2-Deoxyoligosaccharides Enabled by Stereoselective Visible-Light-Promoted Glycosylation.

The photoinitiated intramolecular hydroetherification of alkenols has been used to form C-O bonds, but the intermolecular hydroetherification of alkenes with alcohols remains an unsolved challenge. We herein report the visible-light-promoted 2-deoxyglycosylation of alcohols with glycals. The glycosylation reaction was completed within 2 min in a high quantum yield (ϕ=28.

Electrochemical Bromination of Glycals.

Herein, the convenient one-step electrochemical bromination of glycals using BuNBr as the brominating source under metal-catalyst-free and oxidant-free reaction conditions was described. A series of 2-bromoglycals bearing different electron-withdrawing or electron-donating protective groups were successfully synthesized in moderate to excellent yields. The coupling of tri--benzyl-2-bromogalactal with phenylacetylene, potassium phenyltrifluoroborate, or a 6-OH acceptor was achieved to afford 2C-branched carbohydrates and disaccharides via Sonogashira coupling, Suzuki coupling, and Ferrier rearrangement reactions with high efficiency.

Visible-light-promoted 3,5-dimethoxyphenyl glycoside activation and glycosylation.

A new glycosylation method promoted by visible light with 3,5-dimethoxyphenyl glycoside as the donor was developed. This protocol delivers both -glycosides and -glycosides in moderate to excellent yields using a wide range of -nucleophiles and nucleobases as the glycosyl acceptors.

Electrochemical Trifluoromethylation of Glycals.

Carbohydrates play essential roles in various physiological and pathological processes. Trifluoromethylated compounds have wide applications in the field of medicinal chemistry. Herein, we report a practical and efficient trifluoromethylation of glycals by an electrochemical approach using CFSONa as the trifluoromethyl source and MnBr as the redox mediator.

Novel carbohydrate-triazole derivatives as potential α-glucosidase inhibitors.

A series of novel pyrano[2, 3-d]trizaole compounds were synthesized and their α-glucosidase inhibitory activities were evaluated by in vitro enzyme assay. The experimental data demonstrated that compound 10f showed up to 10-fold higher inhibition (IC74.0 ± 1.

Carbocyclic Ring Closure of Aryl -Glycosides Promoted by Fluoroboric Acid.

A novel transformation from rhamnose-type -glycosides to 2-cyclopentenones is described. With the promotion of fluoroboric acid, -glycosides underwent ring opening and subsequent Nazarov cyclization to afford 2-cyclopentenones in good to excellent yields. The solvent and the concentration of acid are crucial to the yield of this transformation.

Stereoselective Electro-2-deoxyglycosylation from Glycals.

We report a novel and highly stereoselective electro-2-deoxyglycosylation from glycals. This method features excellent stereoselectivity, scope, and functional-group tolerance. This process can also be applied to the modification of a wide range of natural products and drugs.

C-Glycosylation enabled by N-(glycosyloxy)acetamides.

The C-glycosylation of C-nucleophiles including allyltrimethylsilane, silyl enol ethers and phenols with N-(glycosyloxy)acetamides as glycosyl donors has been realized. This protocol provides a convenient and practical route for the synthesis of alkyl C-glycosides and aryl 2-deoxy-β-C-glycosides under mild reaction conditions.

O-Glycosylation Enabled by N-(Glycosyloxy)acetamides.

A novel glycosylation protocol has been established by using N-(glycosyloxy)acetamides as glycosyl donors. The N-oxyacetamide leaving group in donors could be rapidly activated in the presence of Cu(OTf) or SnCl under microwave irradiation. This glycosylation process afforded the coupled products in high yields, and the reaction enjoyed a broad substrate scope, even for disarmed donors and hindered acceptors.

Stereocontrolled Synthesis of 2-Deoxy- C-glycopyranosyl Arenes Using Glycals and Aromatic Amines.

An efficient and stereoselective one-pot, two-step tandem α-arylation of glycals from readily available aryl amines via stable diazonium salts has been developed. Moreover, the stereoselective preparation of the challenging β- C-glycosyl arenes by the anomerization of α- C-glycosides using HBF is also described. This protocol has a broad substrate scope and a wide functional-group tolerance.

Synthesis and Antigenic Evaluation of Oligosaccharide Mimics of Vi Antigen from Salmonella typhi.

Salmonella typhi is responsible for typhoid fever, which is a serious health threat in developing countries. As a virulent factor of Salmonella typhi, the purified Vi polysaccharide (Vi PS) has become an effective vaccine to combat typhoid fever. The chemical synthesis can provide homogeneous and well-defined molecules for the development of Vi-based vaccines.

Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units.

Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency.

2-Trifluoromethylthiolation of glycals.

Methods for trifluoromethylthiolation are very limited. To tackle this problem, a mild and efficient approach to the 2-trifluoromethylthiolation of glycals has been developed. This protocol employed N-trifluoromethylthiosaccharin as the trifluoromethylthiolating reagent, TMSCl as the activator, and DBU as the base, affording 2-trifluoromethylthioglycals in good yields.

Visible Light Photoredox-Catalyzed O-Sialylation Using Thiosialoside Donors.

An efficient protocol for the O-sialylation using thiosialoside donors under visible light photocatalysis was developed. Thiosialosides were activated under the irradiation with blue light in the presence of Ru(bpy)3(PF6)2 as photocatalyst, Umemoto's reagent as CF3 radical source and Cu(OTf)2 as an additive in acetonitrile/dichloromethane at -30 °C, and the subsequent reaction with glycosyl acceptors generally produced the desired sialosides in good to excellent yields with the satisfactory α-selectivity.

Stereoselective Koenigs-Knorr Glycosylation Catalyzed by Urea.

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases.

Nitro-polyols via Pyridine Promoted C═C Cleavage of 2-Nitroglycals. Application to the Synthesis of (-)-Hyacinthacine A1.

A mild and convenient transformation for the synthesis of nitro-polyols is described. The nitro-polyol derivatives were prepared either from 2-nitroglycals via a pyridine-promoted scission of the carbon-carbon double bond or from glycals via a sequential nitration-scission procedure. The generated nitro-polyols could undergo a stereoselective Michael addition reaction.

Direct C-H Trifluoromethylation of Glycals by Photoredox Catalysis.

A mild, efficient, and practical transformation for the direct C-H trifluoromethylation of glycals under visible light has been reported for the first time. This reaction employed fac-Ir(3+)(ppy)3 as the photocatalyst, Umemoto's reagent as the CF3 source, and a household blue LED or sunlight as the light source. Glycals bearing both electron-withdrawing and -donating protective groups performed this reaction smoothly.

Photoinduced C-S Bond Cleavage of Thioglycosides and Glycosylation.

A glycosyl coupling reaction via photoinduced direct activation of thioglycosides and subsequent O-glycosylation in the absence of photosensitizer was developed for the first time. This reaction underwent a selectively homolytic cleavage of a C-S bond to generate a glycosyl radical, which was oxidized to an oxacarbenium ion by Cu(OTf)2, and a sequential O-glycosylation. A wide range of glycosides were synthesized in moderate to excellent yield using sugars, amino acids, or cholesterol as the acceptors.

Highly Substituted Cyclopentane-CMP Conjugates as Potent Sialyltransferase Inhibitors.

Sialylconjugates on cell surfaces are involved in many biological events such as cellular recognition, signal transduction, and immune response. It has been reported that aberrant sialylation at the nonreducing end of glycoconjugates and overexpression of sialyltransferases (STs) in cells are correlated with the malignance, invasion, and metastasis of tumors. Therefore, inhibitors of STs would provide valuable leads for the discovery of antitumor drugs.