An Open-Air Palladium-Catalyzed Stereoselective O-Glycosylation of Glycals via in-situ Generation of gem-Disubstituted Methanols from p-Quinone Methides.

We devised a palladium-catalyzed α-stereoselective glycosylation that incorporates oxygen via in-situ generation of gem-disubstituted methanols from p-quinone methides to access 2,3-unsaturated gem-diarylmethyl O-glycosides under open-air atmosphere at room temperature. Advantages of this environmentally friendly strategy include the absence of additives and ligands, using water as the green source of oxygen, mildest, operationally simple, exhibiting a wide functional group tolerance, and compatibility with a variety of glycal progenitors in appreciable yields. A mechanistic study has been verified via H2 18 O labeling, which validates that water (moisture) is a sole source of oxygen.

Mild method for the synthesis of α-glycosyl chlorides: A convenient protocol for quick one-pot glycosylation.

A simple and efficient protocol for the preparation of α-glycosyl chlorides within 15-30 min is described which employs a stable, cheap, and commercially available Trichloroisocyanuric acid (TCCA) as non-toxic chlorinating agent along with PPh3. This process involved a wide range of substrate scope and is well-suited with labile hydroxyl protecting groups such as benzyl, acetyl, benzoyl, isopropylidene, benzylidene, and TBDPS (tert-butyldiphenylsilyl) groups. This process is operationally simple, mild conditions and obtained good yields with excellent α selectivity. Moreover, a multi-catalyst one-pot glycosylation can be carried out to transform the glycosyl hemiacetals directly to a various O-glycosides in high overall yields without the need for separation or purification of the α-glycosyl chloride donors.

Atom-Economic Synthesis of Unsymmetrical gem-Diarylmethylthio/Seleno Glycosides via Base Mediated C(O)-S/Se Bond Cleavage and Acyl Transfer Approach of Glycosylthio/Selenoacetates.

Herein, we invented the Cs2CO3-mediated atom economic method that streamlines the scission of the C(O)-S/Se bond involving the in situ generation of an anomeric thiolate/selenolate anion, which reacted with p-QMs to yield novel unsymmetrical gem-diarylmethylthio/seleno glycosides while retaining the anomeric stereochemistry. Notably, the key features of this protocol involve unprecedented long-range acyl transfer (from S/Se to O), thus affording acylation of the final product which is not yet reported by classical methods. This straightforward protocol offers a mild, short reaction time, synthetically simple approach, and compatibility with 8 types of sugar along with phenylthio/benzylseleno esters.

Palladium-Catalyzed Direct C-H Glycosylation of Free (N-H) Indole and Tryptophan by Norbornene-Mediated Regioselective C-H Activation.

We describe the palladium-catalyzed direct C-H glycosylation of free N-H indole or tryptophan for the stereoselective synthesis of 2-glycosylindoles and tryptophan-C-glycosides. This reaction relies on the ortho-directing transient mediator norbornene, which underwent regioselective C-H functionalization at the indole or tryptophan ring, providing high chemoselectivity. This method offers a more straightforward, step-economical, and cost-effective route to construct C-glycosides. The gram-scale amenable building blocks can be further functionalized at C3 and N-H, displaying the robustness of present method.

Catalyst- and Base-free One-pot, Multicomponent, De Novo Assembly of Structurally Diverse Morpholine Glycoconjugates.

A catalyst-, metal- and base-free unprecedented one-pot multicomponent synthetic strategy has been established for the construction of various substituted morpholine glycoconjugates through four-component reactions of glycosyl amino alcohol, chloroacetone, acid, and isocyanides. Unexpectedly, this one-pot approach generates only the cyclized morpholine scaffolds rather than normal Ugi adduct without any external base. This reaction proceeds via in situ formations of Schiff-base followed by an intramolecular halogen displacement process, finally the Joullie-Ugi reaction takes place leading to the corresponding products with a mixture of diastereomers.

Glycosyl 3-Phenyl-4-pentenoates as Versatile Glycosyl Donors: Reactivity and Their Application in One-Pot Oligosaccharide Assemblies.

Both glycoconjugates and oligosaccharides are important biomolecules having significant roles in several biological processes, and a new strategy for their synthesis is crucial. Here, we report a versatile N-iodosuccinimide/trimethylsilyl triflate (NIS/TMSOTf) promoted glycosidation approach with shelf-stable 3-phenyl-4-pentenoate glycosyl as a donor for the efficient synthesis of O/C-glycosides with free alcohols, silylated alcohols, and C-type nucleophile acceptors in good to excellent yields. The mild activation conditions and outstanding reactivity of phenyl substituted pentenoate donors analogous to 4-pentenoate glycosyl donors enhance their applicability to various one-pot strategies for the synthesis of oligosaccharides, such as single-catalyst one-pot and acceptor reactivity-controlled one-pot strategies.

4,5-Dioxo-imidazolinium Cation-Promoted α-Selective Dehydrative Glycosylation of 2-Deoxy- and 2,6-Dideoxy Sugars.

Herein, we report the great potential of the 4,5-dioxo-imidazolinium cation activation strategy for dehydrative glycosylation reactions employing the readily available and economical geminal dichloroimidazolidinediones (DCIDs) that promotes the glycosylation between 2-deoxy- and 2,6-dideoxy-sugar hemiacetals with various acceptors in good yields and high α-selectivity. This research not only provides a mild and efficient alternative approach for stereoselective dehydrative glycosylation but also extends the dichloroimidazolidinedione as a novel promoter in the field of glycoscience.

Recent advances in palladium-catalyzed C(sp3)/C(sp2)-H bond functionalizations: access to C-branched glycosides.

Over the recent decades, tremendous interest has developed in the transformation of complex substrates by C-H activation and functionalization. In particular, palladium-catalyzed directing and non-directing group-assisted C-H functionalization has emerged as a powerful avenue to access C-branched glycosides. Due to the extreme complexity, delicate functionalities, and high stability of C-H bonds, site-selective functionalization of carbohydrate under mild conditions is highly desirable. The purpose of this review is to cover most of the recent advances in palladium-catalyzed C(sp3) and C(sp2)-H bond functionalizations for the synthesis of C-branched glycosides along with future directions.

Tris(pentafluorophenyl)borane-Catalyzed Stereoselective C-Glycosylation of Indoles with Glycosyl Trichloroacetimidates: Access to 3-Indolyl-C-glycosides.

An efficient and highly regioselective method for the synthesis of 3-indolyl-C-glycosides has been developed through coupling of glycosyl trichloroacetimidates with a wide range of substituted indoles in the presence of catalytic amounts of B(C6F5)3 within a few minutes. This methodology has a wide scope of substrates under mild reaction conditions and provides exclusively ß-stereoselective 3-indolyl-C-glycosides in 64-87% yields.

Bacterial surface capsular polysaccharides from Streptococcus pneumoniae: A systematic review on structures, syntheses, and glycoconjugate vaccines.

The polysaccharide capsule of Streptococcus pneumoniae constitutes the outermost surface structure of the organism and plays a critical role in virulence. The capsule is the target of current pneumococcal vaccines and glycoconjugates and has important medical and industrial applications. Widespread use of these vaccines is driving changes in serotype prevalence in disease. A massive array of sugars and glycosidic linkages experienced with complete diversity of potential polysaccharide structures. However, it is impossible to collect a sufficient quantity of glycan antigens for the preparation of CPS-based glycoconjugate vaccines from natural sources with high purity and for thorough biological evaluation. So nowadays, the development of a chemical synthetic strategy and their conjugation with a carrier protein to form synthetic glycoconjugate vaccines has been used to gain access on a large scale. This review provides a comprehensive summary of structures, synthesis as well as recent development of synthetic glycoconjugate vaccines, which will support research and may benefit the glycochemical and medical sciences.

Intramolecular 6-exo-dig Post-Ugi Cyclization of N-Substituted 2-Alkynamides: Direct Access to Functionalized Morpholinone Glycoconjugates.

We herein report a chemo- and regioselective 6-exo-dig catalytic cyclization of Ugi adducts N-substituted 2-alkynamides to access functionalized morpholinone glycoconjugates in the presence of triphenylphosphine. This array allows an interesting multicomponent access to a library of functionalized morpholinone glycoconjugates under mild reaction conditions with regeneration of catalyst triphenylphosphine, supported by 31P nuclear magnetic resonance studies. Density functional theory shows the 6-exo-dig oxocyclization pathway is preferred, which supports our experimental observation.

Metal-free [3+2] cycloaddition of glycosyl olefinic ester with in situ generated CF3CHN2: Access to CF3-substituted pyrazoline glycoconjugates.

An efficient [3 + 2] cycloaddition of glycosyl olefinic ester with in situ generated CF3CHN2 for the syntheses of CF3-substituted pyrazoline glycoconjugate has been developed. This mild, one-pot reaction condition avoiding the use of metallic catalyst and additive will be useful in the pharmaceutical industry. This reaction features are the broad substrate scope, good functional group tolerance with good to high yields.

Chiral auxiliaries: Usefullness in stereoselective glycosylation reactions and their synthetic applications.

Oligosaccharides play a very important role in biological system and structure-activity relationships that is why it has a lot of application to medicinal chemistry and development of polysaccharide conjugate vaccines. The stereoselective introduction of a glycosidic linkage presents the principal challenge for biological importance oligosaccharide synthesis. The main aim of this review is to described the importance of chiral auxiliary and neibhouring group participation for the stereoselective 1,2-cis glycosidic bonds formation and their application in complex oligosaccharide synthesis.Numerous 1,2-cis-linked oligosaccharides and glyconjugates are naturally found in the compounds of blood group, human milk, antigens of bacterial lipopolysaccharide etc.that predominantly increased it's importance in this field.

The strategic use of para-quinone methides to access synthetically challenging and chemoselective α,α'-diarylmethyl N-glycosides from unprotected carbohydrate amines.

Reported herein is a practical route to access synthetically challenging and chemoselective α,α'-diarylmethyl N-glycosides via Sc(OTf)3-catalyzed 1,6-conjugate addition of amino sugars with para-quinone methides (p-QMs). The reactions proceed smoothly without a base and under mild reaction conditions with a broad substrate scope and moderate to good yields.

An eco-friendly N-benzoylglycine/thiourea cooperative catalyzed stereoselective synthesis of ß-L-rhamnopyranosides.

A new practical utility for ß-stereoselective L-rhamnopyranosylations are conducted using rhamnosyl trichloroacetimidate donors in the presence of N-benzoylglycine/thiourea cooperative catalysis. This method represents the first instance where amino acid derivative N-benzoylglycine is used as a catalyst for ß-L-rhamnopyranosylations. This method represents the first instance where environmentally benign amino acid derivative, such as N-benzoylglycine which is reported as less toxic and can be used as efficient catalyst for smooth transformation under eco friendly conditions. On the other hand ß-stereoselectivity of rhamnosyl trichloroacetimidate donors protected with O-picoloyl groups at remote positions (C-2 and C-3) has been investigated while the glycosylation reactions of 2-O-picoloyl group substituted l-rhamnosyl donor displays predominant ß-stereoselectivity. Reaction proceeded smoothly with moderate to high yield under mild reaction conditions at room temperature with 10 mol% catalyst loadings and tolerant of a wide range of glycoside acceptors.

Synthesis of Structurally Diverse Substituted Aziridinyl Glycoconjugates via Base-Mediated One-Pot Post-Ugi Cyclization.

The base-promoted intramolecular cyclization of Ugi-azide adduct has been demonstrated for the synthesis of highly substituted aziridinyl glycoconjugates in one pot. The reactions are scalable and efficient and have an operationally simple broad substrate scope. To gain insight into the mechanism of aziridine formation, DFT and control experiments show that the cyclization of the aziridine glycoconjugate pathway was preferred, as it proceeds with a low activation energy barrier (0.57 kcal mol-1), which supports our experimental observation.

HDAC as onco target: Reviewing the synthetic approaches with SAR study of their inhibitors.

Even though one is moving towards the success in the discovery of efficient anti-cancer molecules, the drugs used in the treatment of various malignancies are found to possess toxicity and adverse reactivity in the human body that limit their use. The scientists all over the world are engaged in bringing up strategies that aim to develop small molecules that target the abnormal epigenetic factors. The discovery of the role of Histone deacetylases (HDACs) has promised to be a turning point in the treatment of various malignancies. Thus, the invention of potent and safe anticancer therapeutics agents with minimal adverse and side effects are still a major topic of concern and a huge number of research works have been reported in the past few years. This review has been written to discuss on the influence of Histone Deacetylases in cancer malignancies. We have tried to embrace majority of the developments made till date in the field of HDAC and its inhibitors herein. The drugs that are clinically applied, synthesis and SAR study that highlight the chemical groups responsible for evoking the HDAC inhibition and potential of various new classes of HDAC inhibitors (synthetic, hybrid and natural) have also been included.

An expeditious synthesis of blood-group antigens, ABO histo-blood group type II antigens and xenoantigen oligosaccharides with amino type spacer-arms.

Blood group oligosaccharides are one of the most clinically important antigen families and they may also act as secondary ligands for bacterial toxins from Escherichia coli and Vibrio cholerae. Herein we report the synthesis of spacered (sp = CH2CH2CH2NH2) glycosides of A antigen {α-D-GalNAc-(l→3)-[α-L-Fuc-(l→2)]-ß-D-Gal-}, B antigen{α-D-Gal-(l→3)-[α-L-Fuc-(l→2)]-ß-D-Gal-}, LewisX{α-D-Gal-(l→4)-[α-L-Fuc-(l→3)]-ß-D-GlcNAc-}, A type-II {α-D-GalNAc-(l→3)-[α-L-Fuc-(l→2)]-ß-D-Gal-(1→4)-ß-D-GlcNAc-}, B type-II {α-D-Gal-(l→3)-[α-L-Fuc-(l→2)]-ß-D-Gal-(1→4)-ß-D-GlcNAc-}, H type-II{α-L-Fuc-(l→2)-ß-D-Gal-(1→4)-ß-D-GlcNAc-}, xenoantigen {α-D-Gal-(l→3)-ß-D-Gal-(1→4)-[α-L-Fuc-(l→2)]-ß-D-GlcNAc-} and Linear B Type II {α-D-Gal-(l→3)-ß-D-Gal-(1→4)-ß-D-GlcNAc-} useful for a range of biochemical investigations. This linker was chosen so as to facilitate the future conjugation of the antigens to proteins or other molecules. We also measured the affinities of some synthesized oligosaccharides against El Tor CTB strain from V. cholera.

Synthesis and biotinylation of oligosaccharide fragments of mannosylated and 5-deoxy-5-methylthio-xylofuranosylated lipoarabinomannan from Mycobacterium tuberculosis.

The attachment of biotin to a molecule provides a powerful tool in biology. Here, we report an efficient synthesis and biotinylation of mannosylated and 5-deoxy-5-methylthio-xylofuranosylated Lipoarabinomannan from Mycobacterium tuberculosis. Preparation of the oligosaccharides involved the sequential addition of thioglycoside donors with arabinofuranosyl-containing acceptors. Methylthio group was introduced near the end of the synthesis.