Synthesis Of Glycosides Research Articles

Tellurium in carbohydrate synthesis

Abstract In this article, we discuss about the influence of tellurium in carbohydrate synthesis. Mainly the chapter focuses on the importance of the tellurium during the synthesis of glycosides and during the oxidation of glucose.

Total Synthesis of Starfish Cyclic Steroid Glycosides

AbstractStarfishes have evolved with a special type of secondary metabolites, namely starfish saponins, to ward off various predators and parasites; among them, the starfish cyclic steroid glycosides stand out structurally, featuring a unique 16‐membered ring formed by bridging the steroidal C3 and C6 with a trisaccharide. The rigid cyclic scaffold and the congested and vulnerable steroid‐sugar etherate linkage present an unprecedented synthetic challenge. Here we report a collective total synthesis of the major starfish cyclic steroid glycosides, namely luzonicosides A (1) and D (2) and sepositoside A (3), with an innovative approach, which entails a de novo construction of the ether‐linked hexopyranosyl units, use of olefinic pyranoses as sugar precursors, and a decisive ring‐closing glycosylation under the mild gold(I)‐catalyzed conditions.

Total Synthesis of Starfish Cyclic Steroid Glycosides.

Starfishes have evolved with a special type of secondary metabolites, namely starfish saponins, to ward off various predators and parasites; among them, the starfish cyclic steroid glycosides stand out structurally, featuring a unique 16-membered ring formed by bridging the steroidal C3 and C6 with a trisaccharide. The rigid cyclic scaffold and the congested and vulnerable steroid-sugar etherate linkage present an unprecedented synthetic challenge. Here we report a collective total synthesis of the major starfish cyclic steroid glycosides, namely luzonicosides A (1) and D (2) and sepositoside A (3), with an innovative approach, which entails a de novo construction of the ether-linked hexopyranosyl units, use of olefinic pyranoses as sugar precursors, and a decisive ring-closing glycosylation under the mild gold(I)-catalyzed conditions.

Glycosyl Vinylogous Carbonates as Glycosyl Donors by Metal-Free Activation.

Synthesis of glycoconjugates employs a glycosylation reaction wherein an electrophile and a nucleophile known as a glycosyl donor and an aglycon, respectively, are involved. Glycosyl donors often contain a leaving group at the anomeric carbon that upon reaction with activator(s) results in a highly reactive electrophilic species reported as an oxycarbenium ion contact pair that will then be attacked by the aglycon. Therefore, identification of the correct glycosyl donor and activation protocol is essential for the synthesis of all glycoconjugates. Recently identified [Au]/[Ag]-catalyzed activation of ethynylcyclohexyl glycosyl carbonates is one such versatile method for the synthesis of glycosides, oligosaccharides, and glycoconjugates. In this work, stable glycosyl vinylogous carbonates were identified to undergo glycosidation in the presence of a sub-stoichiometric quantity of TfOH. The reaction is fast and suitable for donors containing both C2-ethers and C2-esters. Donors positioned with C2-ethers resulted in anomeric mixtures with greater selectivity toward 1,2-cis glycosides, whereas those with C2-esters gave 1,2-trans selective glycosides. The versatility of the method is demonstrated by conducting the glycosylation with more than 25 substrates. Furthermore, the utility of the glycosyl vinylogous carbonate donors is demonstrated with the successful synthesis of the branched pentaarabinofuranoside moiety of the Mycobacterium tuberculosis cell wall.

Design and Synthesis of α-Anomeric Diacetylene-Containing Glycosides as Photopolymerizable Molecular Gelators.

Glycolipids with diacetylene functional groups are fascinating compounds with many practical uses. Among these, diacetylene-containing gelators are especially important because they can form photopolymerizable gels, which are useful stimuli-responsive materials. Inspired by the unique properties of diacetylene-containing gelators and to understand the structural influences especially the location of the diacetylene functional groups on the self-assembling properties, a series of 15 novel N-acetyl-d-glucosamine derivatives with the diacetylene functional group introduced at the anomeric position were designed and synthesized. The diacetylene function is attached to the sugar through α-glycosylation with the distance from the anomeric oxygen being varied from one, two, and three methylene groups, and the other side contains hydroxyl, carboxyl, phenyl, and alkyl substituents. Remarkably, all compounds can form self-assembled gels in one or more selected solvents. A majority of these synthesized diacetylene glycosides are effective gelators for ethanol/water (v/v 1:1), dimethyl sulfoxide/water (v/v 1:1), and toluene, and one compound also formed a hydrogel at 1.0 wt %. Typically, these glycosides form gels that are photopolymerizable to afford red-colored gels. Scanning electronic microscopy indicated that the gelators formed helices, fibers, and planar sheet-like morphologies. The chemical structures of the derivatives affected their gelation properties and responses to UV treatment. The carboxylic acid-functionalized derivative 17 was able to immobilize basic solutions and form transparent gels. We expect that these diacetylene glycosides especially the hydroxyl and carboxylic acid derivatives will be useful as stimuli-responsive glycolipids for biomedical research.

Evolution of a Reagent-Controlled Strategy for β-Selective C-Glycoside Synthesis

Abstract C-Alkyl glycosides represent an attractive class of nonhydrolyzable carbohydrate mimetics which possess enormous potential as next-generation therapeutics. Methods for the direct stereoselective synthesis of C-alkyl glycosides with a broad substrate tolerance are limited, however. This is especially in the case of β-linked C-alkyl glycosides, where direct methods for synthesis from commonly available coupling partners remain limited. This Account describes the evolution of our laboratory’s studies on glycosyl sulfonate chemistry from a method for the construction of simple β-linked 2-deoxy-sugars to a technology for the direct synthesis of β-linked acyl and homoacyl glycosides that can be elaborated into more complex structures.1 Introduction2 Glycosyl Sulfonates3 Glycosyl Sulfonates in Oligosaccharide Synthesis4 Matching Donor and Sulfonate Reactivity5 β-Linked C-Acyl and Homoacyl Glycoside Synthesis6 Elaboration to other Products7 Conclusion

Solvent‐Free Synthesis of Glycoside Annulated 1,2,3‐Triazole Based Dihydropyrimidinones using Copper Ferrite Nanomaterials as Heterogeneous Catalyst and DFT Studies

AbstractIn the present study, We have developed a facile and efficient method for the one‐pot five component synthesis of glycoside annulated 1,2,3‐triazole based dihydropyrimidinone derivatives using copper ferrite nanomaterials in the present work as heterogeneous catalyst. The quantum chemical investigations for the synthesized compounds have been carried out at the DFT/B3LYP/6‐31G(d) level of theory to predict the optimized geometry and different molecular properties. Frontier molecular orbitals, global reactivity descriptors, molecular electrostatic potential map, and thermodynamic parameters have also been reported at the same level of theory.

Multigram scale preparation of a semi-synthetic N-trifluoroacetyl protected chondroitin disaccharide building block: Towards the stereoselective synthesis of chondroitin sulfates disaccharides

The chemoselective N-trifluoroacetylation of a chondroitin disaccharide obtained from controlled acid hydrolysis of a commercially available polymeric chondroitin sulfate is reported for the first time. We also described the multi-gram scale synthesis of a donor block having a benzylidene moiety further used for the expeditious and stereocontrolled synthesis of glycosides fitted with various aglycons. Stereocontrolled β-glycosylation, sulfation and efficient N-TFA deprotection steps afforded the desired disaccharides in good yields.

A Fungal Versatile GH10 Endoxylanase and Its Glycosynthase Variant: Synthesis of Xylooligosaccharides and Glycosides of Bioactive Phenolic Compounds.

The study of endoxylanases as catalysts to valorize hemicellulosic residues and to obtain glycosides with improved properties is a topic of great industrial interest. In this work, a GH10 β-1,4-endoxylanase (XynSOS), from the ascomycetous fungus Talaromyces amestolkiae, has been heterologously produced in Pichia pastoris, purified, and characterized. rXynSOS is a highly glycosylated monomeric enzyme of 53 kDa that contains a functional CBM1 domain and shows its optimal activity on azurine cross-linked (AZCL)–beechwood xylan at 70 °C and pH 5. Substrate specificity and kinetic studies confirmed its versatility and high affinity for beechwood xylan and wheat arabinoxylan. Moreover, rXynSOS was capable of transglycosylating phenolic compounds, although with low efficiencies. For expanding its synthetic capacity, a glycosynthase variant of rXynSOS was developed by directed mutagenesis, replacing its nucleophile catalytic residue E236 by a glycine (rXynSOS-E236G). This novel glycosynthase was able to synthesize β-1,4-xylooligosaccharides (XOS) of different lengths (four, six, eight, and ten xylose units), which are known to be emerging prebiotics. rXynSOS-E236G was also much more active than the native enzyme in the glycosylation of a broad range of phenolic compounds with antioxidant properties. The interesting capabilities of rXynSOS and its glycosynthase variant make them promising tools for biotechnological applications.

Citric acid mediated simple and stereoselective synthesis of o-linked glycosides by Ferrier rearrangement

A simple and environment-friendly citric acid-mediated synthesis of glycosides has been reported using Ferrier-rearrangement. Using this protocol, synthesis of several glycosides including pseudo disaccharides was prepared. Citric acid was successfully employed for the synthesis of glycosides from D-glucal, L-rhamnal, D-xylal and D-galactal with various alcohols to give a broad range of glycosides in up to 80% yields with α-isomer as major product under mild reaction conditions.

Sustainable production of rare oleanane-type ginsenoside Ro with an artificial glycosylation pathway in Saccharomyces cerevisiae

S. cerevisiae was genetically reprogrammed to produce ginsenoside Ro with seven exogenous enzymes from five species. This study also paved a good way for the synthesis of other complex glycosides of triterpenoids.

The syntheses of polymethoxy flavonoid glycosides from apigenin and diosmetin and their cytotoxic activities on two human cancer cell lines

The syntheses of a series of polymethoxy flavonoids glycosides were performed via reactions of bromination, Ullmann aromatic nucleophilic substitution, O-methylation, dimethyldioxirane (DMDO) oxidation, glycosidation and then deprotected, starting from abundant and inexpensive natural sources Apigenin and Diosmetin. This new synthetic route has many advantages such as easy availability of starting materials, simple performance, and good yields. All the compounds were tested for their anticancer activities against breast cancer (MCF-7) and HeLa cancer cell lines using CCK-8 assay. The results showed that most of the target compounds exhibited moderate to potent antiproliferative activities on MCF-7 and HeLa cells compared to the positive control cis-platin. Polyethoxy flavonoids glycosides (PFG) have been shown to improve the proliferation inhibitions on HeLa and MCF-7 cells as well as increase the water solubilities in comparison to those of polymethoxy flavonoids. The structures of the synthesized compounds have also been determined using NMR (1H, 13C), MS and HRMS.

Preparation of glycosyl carboxylic acids via stereoselective synthesis and oxidative cleavage of C-vinyl glycosides.

We have developed an improved cyanide-free strategy for the synthesis of glycosyl carboxylic acids, employing stereoselective C-vinyl glycosylation and oxidative cleavage of C-vinyl glycosides as key steps. Compared to our previous work, the amount of NaIO4 required for the oxidative cleavage step is reduced significantly from 18 equivalents to 4.5 equivalents. This modification not only is advantageous in terms of operation and costs but also avoids the over-oxidation problem, thus greatly expanding the substrate scope, which is evidenced by the fact that 10 out of 21 glycosyl carboxylic acids synthesized are undocumented. With differently O5-protected furanosyl acids in hand, we demonstrate that an electron-rich protecting group is beneficial for the decarboxylative arylation of furanosyl carboxylic acids. This represents a rare example of protecting groups affecting the reaction efficiency in radical C-glycosylation. As C-vinyl glycosides can be prepared stereoselectively and the oxidative step is stereoretentive, the approach provides an effective means to access 1,2-trans or 1,2-cis glycosyl acids, which would be a valuable alternative to the cyanide-based synthesis of glycosyl carboxylic acids.

Enzymatic synthesis of vitexin glycosides and their activity.

Vitexin is an active component of many traditional chinese medicines, and is found in various plants. The low solubility of vitexin limits its pharmaceutical usage. In this study, solvent-stable β-fructosidase was used to glycosylate vitexin in organic solvents. The β-fructosidase showed high activity and stability in 30–80% (v/v) ethyl acetate with 90–99% yields of vitexin glycosides. Highly efficient synthesis of β-d-fructofuranosyl-(2→6)-vitexin (1.04 g L−1) and β-d-difructofuranosyl-(2→6)-vitexin (0.45 g L−1) was attained in 50% (v/v) ethyl acetate solvent system from 1.5 g L−1 vitexin. Two novel vitexin glycosides showed higher anti-tumor activities compared to that of vitexin by employing a human breast cancer cytotoxicity assay.

8-(Methyltosylaminoethynyl)-1-naphthyl (MTAEN) Glycosides: Potent Donors in Glycosides Synthesis.

With 8-(methyltosylaminoethynyl)-1-naphthyl (MTAEN) glycoside as donors, a novel and efficient glycosylation protocol has been established. The MTAEN glycosylation protocol exhibits the merits of shelf-stable donors, mild catalytic promotion conditions, considerably extended substrate scope encompassing both free alcohols, silylated alcohols, nucleobases, primary amides, and C-type nucleophile acceptors, and applicability to various one-pot strategies for highly efficient synthesis of oligosaccharides, such as orthogonal one-pot, single-catalyst one-pot, and acceptor reactivity-controlled one-pot strategies.

Application of immobilized glycosidase in the synthesis of glycoside compounds

Glycoside compounds are widely used in medicine, food, surfactant, and cosmetics. The glycosidase-catalyzed synthesis of glycoside can be operated at mild reaction conditions with low material cost. The glycosidase-catalyzed processes include reverse hydrolysis and transglycosylation, appropriately reducing the water activity in both processes may effectively improve the catalytic efficiency of glucosidase. However, glucosidase is prone to be deactivated at low water activity. Thus, glucosidase was immobilized to maintain its activity in the low water activity environment, and even in neat organic solvent system. This article summarizes the advances in glycosidase immobilization in the past 30 years, including single or comprehensive immobilization techniques, and immobilization techniques combined with genetic engineering, with the aim to provide a reference for the synthesis of glycosides using immobilized glycosidases.

Stevia rebaudiana Bertoni: The Interaction of Night Interruption on Gas Exchange, Flowering Delay, and Steviol Glycosides Synthesis

The Stevia market is estimated to be USD 1.14 billion in 2028 due to its acceptance in the food and beverage industry. Stevia rebaudiana and its two more relevant edulcorants: stevioside (St) and rebaudioside A (Reb-A) can reach 450-fold sweeter than sucrose. The species is considered a long night plant, promoting flowering and shortening vegetative growth. Thus, to increase the leaf area and St and Reb-A increase, we broke the long night with a short light pulse, here called night interruption (NI). In this study, three NI times and two S. rebaudiana genotypes were tested to promote larger vegetative growth, flowering delay, and higher synthesis of steviol glycosides (SvGly). The main goal of this study was to demonstrate that NI increased net photosynthesis (9% to 20%), the internode length (59%), the leaf area (25%), while delays in 4 to 10 days of the flowering phase, impacting in 17% to 25% more St and Reb-A, respectively. Here we describe an inexpensive flowering delay, elongation of vegetative growth, allowing extended harvesting, which could yield four to five annual harvesting of leaves, increasing the production in 21% to 24% more St and Reb-A yield (kg ha−1).

Transglycosylation by β-mannanase TrMan5A variants and enzyme synergy for synthesis of allyl glycosides from galactomannan

Retaining β-mannanases are glycoside hydrolases (GHs) that can potentially be applied for synthesis of glycosides by catalysis of transglycosylation reactions. A novel active-site double mutant (R171K/E205D) of the catalytic module (CM) of the family GH5 Trichoderma reesei β-mannanase (TrMan5A) was expressed in Pichia pastoris and purified. TrMan5A, CM and CM-variants R171K and R171K/E205D had pH optima between pH 4.0–5.3 and showed >80 % remaining activity after incubation at 40 °C for 48 h. The enzymes were screened for transglycosylation capacity toward oligomeric and polymeric donor substrates and alcohol acceptors using mass-spectrometry. Hydrolysis and transglycosylation products were analysed by a novel HPLC procedure using an NH2 column. R171K/E205D was superior in reactions with mannotetraose and the acceptor allyl alcohol, it had twice as high propensity for transglycosylation as wild-type TrMan5A. Wild-type TrMan5A produced the highest amounts of allyl β-mannosides (with 1–3 mannosyls) from locust bean galactomannan. Applying enzyme synergy, adding the GH27 guar α-galactosidase to the reaction (to cleave off galactomannan side-groups), gave a 2.1-fold increase of allyl mannosides and simultaneously a significant production of allyl galactopyranoside, increasing overall yield of allyl glycosides 4.4-fold, from 2.2% to 9.8%. The enzymatic synthesis of reactive allyl glycosides opens up for production of novel biomaterials and glycopolymers.

Controllable Iterative β-Glucosylation from UDP-Glucose by Bacillus cereus Glycosyltransferase GT1: Application for the Synthesis of Disaccharide-Modified Xenobiotics.

Glycosylation in natural product metabolism and xenobiotic detoxification often leads to disaccharide-modified metabolites. The chemical synthesis of such glycosides typically separates the glycosylation steps in space and time. The option to perform the two-step glycosylation in one pot, and catalyzed by a single permissive enzyme, is interesting for a facile access to disaccharide-modified products. Here, we reveal the glycosyltransferase GT1 from Bacillus cereus (BcGT1; gene identifier: KT821092) for iterative O-β-glucosylation from uridine 5′-diphosphate (UDP)-glucose to form a β-linked disaccharide of different metabolites, including a C15 hydroxylated detoxification intermediate of the agricultural herbicide cinmethylin (15HCM). We identify thermodynamic and kinetic requirements for the selective formation of the disaccharide compared to the monosaccharide-modified 15HCM. As shown by NMR and high-resolution MS, β-cellobiosyl and β-gentiobiosyl groups are attached to the aglycone’s O15 in a 2:1 ratio. Glucosylation reactions on methylumbelliferone and 4-nitrophenol involve reversible glycosyl transfer from and to UDP as well as UDP-glucose hydrolysis, both catalyzed by BcGT1. Collectively, this study delineates the iterative β-d-glucosylation of aglycones by BcGT1 and demonstrates applicability for the programmable one-pot synthesis of disaccharide-modified 15HCM.

Glycosyl-Radical-Based Synthesis of C-Alkyl Glycosides via Photomediated Defluorinative gem-Difluoroallylation.

We have developed a stereoselective, glycosyl radical-based method for the synthesis of C-alkyl glycosides via a photomediated defluorinative gem-difluoroallylation reaction. We demonstrate for the first time that glycosyl radicals, generated from glycosyl bromides, can readily participate in a photomediated radical polar crossover process, affording a diverse array of gem-difluoroalkene containing C-glycosides. Notable features of this method include scalability, mild conditions, broad substrate scope, and suitability for the late-stage modification of complex molecules.