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The first highly diastereoselective synthesis of β-anomers of 4’-thionucleosides has been carried out by means of electrophilic glycosidation utilizing 3,5-O-(di-tertbutylsilylene) (DTBS)-4-thiofuranoid glycal as a glycosyl donor. The resulting glycosides were transformed into ribo-, 2’-deoxy-, and arabinofuranosyl nucleosides through a chemical transformation of the 2’-substituent. The additive Pummerer reaction of the glycal Soxide gave 1,2-di-O-acetyl-3,5-O-DTBS-4-thioribofuranose. The utility of the DTBSprotected 4-thioribofuranose has been demonstrated by the preparation of 4’-thio analogues of pyrimidine- and purine-4’-thioribonucleosides based on the Vorbrüggen glycosidation. Synthesis of 4’-thio-counterpart of C-nucleoside antibiotic tiazofurin has also been carried out. α-Face selective hydroboration of 1-C-aryl- or 1-C-heteroaryl-glycals obtained by cross-coupling of 1-tributylstannylglycal has furnished the respective β- anomer of 4’-thio-C-ribonucleosides, including 4’-thio analogue of nucleoside antibiotic pseudouridine and 9-deazaadenosine. On the basis of lithiation chemistry, 1-C- and 2-Ccarbon- carbon-substituted 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3- diyl) (TIPDS)- 4- thiofuranoid glycal were synthesized. These glycals enabled us to prepare 1’-C- and 2’-β- C-carbon-substituted 2’-deoxy-4’-thionucleosides, including thio-counterpart of antitumor nucleoside antibiotic angustmycin C. Furthermore, 1’-C-methyl-4’-thiothymidine emerged as a potent inhibitor of angiogenesis. In addition, 1’-C-methyl-4’-thiothymidine exhibited more potent inhibitory activity against thymidine kinase-deficient mutant of herpes virus than that of ganciclovir. Among the 4’-substituted 4’-thiothymidines, the 4’- C-cyano- and 4’-C-ethynyl derivatives inhibited replication of HIV variant resistant to 3TC (HIVM184V) as potently as HIV-1IIIB. In terms of the value of selectivity index (SI), 4’-C-cyano-4’-thiothymidine showed a 3-fold selective index (SI) than that of the corresponding thymidine derivative. Furthermore, 4’-C-ethynyl-2’-deoxy-4’-thioguanosine has a 20-fold better value (>18,200) than that of 2’-deoxyguanosine counterpart (933). Furthermore, 4’-azido-4’-thiothymidine emerged as a selective and potent anti-EBV agent. In terms of antineoplastic activity, 4’-azido- and 4’-C-fluoromethyl-2’-deoxy-4’-thiocytidine inhibited proliferation of human B-cell (CCRF-SB) and T-cell leukemia (Molt-4) cell lines, although the parent compound 2’-deoxy-4’-thiocytidine did not exhibit any cytotoxicity up to 100 μM. These facts concerning the biological activities suggested that replacement of the furanose oxygen with a sulfur atom is a promising approach for the development of less toxic antiviral and antineoplastic nucleoside antimetabolites. 4’- Thionucleoside also acts as a monomer for oligonucleotides (ONs) therapeutics, exhibiting superior biological properties. Therefore, this review provides a wide range of potential monomers for antisense ON and siRNA.

A total synthesis of the trisaccharide repeat unit of Salmonella serogroup E1 O-antigen is reported. This synthesis features a key β-mannosylation reaction via cesium carbonate-mediated anomeric O-alkylation of a partially protected D-mannose with an L-fucose-derived electrophile for the first time.

Disaccharide donors are key precursors in convergent glycan synthesis strategies. Unexpectedly, we observed that disaccharide thioglycosyl donors containing 1,4-O-linked α-glycosidic bonds are much more reactive than their β-analogues with the same protecting group pattern. Herein, we rationalized that such a difference in their reactivity is attributed to the conformation of the 1,4-O-interglycosidic bond which is controlled by anomeric and exo-anomeric effects. Moreover, the conformational preferences of these donors are dictated by the dihedral angles ϕ and ψ of their interglycosidic linkages and the torsional angle ω of their side chain along the C5-C6 bond. This fundamental research clarifies how the long-range stereoelectronic effects from the nonreducing end sugar can influence the reactivity of the leaving group at the reducing end and the behavior of disaccharide donors thereof.

Modified C-nucleosides have proven to be enormously successful as chemical probes to understand fundamental biological processes and as small-molecule drugs for cancer and infectious diseases. Historically, the modification of the glycosyl unit has focused on the 2'-, 3'-, and 4'-positions as well as the ribofuranosyl ring oxygen. By contrast, the 1'-position has rarely been studied due to the labile nature of the anomeric position. However, the improved chemical stability of C-nucleosides allows the modification of the 1'-position with substituents not found in conventional N-nucleosides. Herein, we disclose new chemistry for the installation of diverse substituents at the 1'-position of C-nucleosides, including alkyl, alkenyl, difluoromethyl, and fluoromethyl substituents, using the 4-amino-7-(1'-hydroxy-d-ribofuranosyl)pyrrolo[2,1-f][1,2,4]triazine scaffold as a representative purine nucleoside mimetic.

3-Methyl-1-sulfonic acid imidazolium trichlorido copper (II) {[Msim]CuCl3} was prepared and used as a new catalyst for the preparation of 5-amino-1H-pyrazole-4-carbonitriles. In this reaction, the pyrazole ring was formed by an anomeric and vinylogous anomeric effect in the structure of the product.

This article describes the studies on regioselective acetal protection of monosaccharide-based diols using chiral phos-phoric acids (CPAs) and their immobilized polymeric variants, (R)-Ad-TRIP-PS and (S)-SPINOL-PS as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various D-glucose, D-galactose, D-mannose and L-fucose derived 1,2-diols, and could be carried in a re-giodivergent fashion depending on the choice of the chiral catalyst. The polymeric catalysts were conveniently recy-cled and reused multiple times for gram scale functionalizations with catalytic loading as low as 0.1 mol%, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 34 regioisomerically pure differentially protected mono- and disaccharide de-rivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of (R)-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected D-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated sub-strates revealed that low-temperature acetalizations happen via syn-addition mechanism, and that the reaction regi-oselectivity exhibits strong dependence on the temperature. The computational studies indicate complex tempera-ture-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and an-other via concerted asynchronous formation of acetal that results in syn-addition products. The computational models also explain the steric factors responsible for the observed C2-selectivities and are consistent with experimentally observed selectivity trends.

Carbohydrate-based low-molecular-weight gelators (LMWGs) are useful classes of compounds due to their numerous applications. Among sugar-based LMWGs, certain peracetylated sugar beta-triazole derivatives were found to be effective organogelators and showed interesting self-assembling properties. To further understand the structural influence towards molecular assemblies and obtain new functional materials with interesting properties, we designed and synthesized a library of tetraacetyl beta-1-triazolyl alkyl-D-glucosides and D-galactosides, in which a two or three carbon spacer is inserted between the anomeric position and the triazole moiety. A series of 16 glucose derivatives and 14 galactose derivatives were synthesized and analyzed. The self-assembling properties of these new triazole containing glycoconjugates in different solvents were analyzed. Several glucose derivatives were found to be effective LMWGs, with compound 7a forming gels in a variety of organic solvents as well as in the presence of metal ions in aqueous solutions. The organogels formed by several compounds were characterized using optical microscopy, atomic force microscopy (AFM) and UV-vis spectroscopy, etc. The co-gels formed by compound 7a with the Fmoc derivative 7i showed interesting fluorescence enhancement upon gelation. Several gelators were also characterized using powder X-ray diffraction and FT-IR spectroscopy. The potential applications of these sugar-based gelators for drug delivery and dye removal were also studied.

A comprehensive exploration of the anomeric and Perlin effects in a series of 2-substituted-2-fluorotetrahydro-2H-pyrans employing sensitive structural, energetic, and NMR probes calculated by density functional theory (DFT) and natural bond orbital (NBO) approaches is undertaken. We used a wide variety of X substituents exhibiting diverse electronic features (σ-donors, σ-donors/π-donors, and σ-donors/π-acceptors). It is noteworthy that a group of 8 substituents (NHMe, SCN, OBr, NO3, OCl, Cl, OF, and Br) favor the axial conformations, while a group of 13 substituents (NO2, NF2, NH2, CN, SH, H, N3, B(OH)2, OMe, BH2, OH, Me, and Ph) favor the equatorial conformations. Interestingly, a group of 6 substituents (NH2, NHMe, NF2, OF, OCl, and OBr) are responsible for the observed normal Perlin effect while the remaining 16 substituents induce the reverse Perlin effect. An exhaustive investigation of possible correlations of anomeric and Perlin effect descriptors with structural, energetic, one-bond 1JC-F couplings and the nucleophilicity of X descriptors demonstrated the general relationship of the Perlin and anomeric effects and manifested their common stereoelectronic origin.

Galectins are widely expressed galactose-binding lectins implied, for example, in immune regulation, metastatic spreading, and pathogen recognition. N-Acetyllactosamine (Galβ1-4GlcNAc, LacNAc) and its oligomeric or glycosylated forms are natural ligands of galectins. To probe substrate specificity and binding mode of galectins, we synthesized a complete series of six mono-deoxyfluorinated analogues of LacNAc, in which each hydroxyl has been selectively replaced by fluorine while the anomeric position has been protected as methyl β-glycoside. Initial evaluation of their binding to human galectin-1 and -3 by ELISA and 19 F NMR T2 -filter revealed that deoxyfluorination at C3, C4' and C6' completely abolished binding to galectin-1 but very weak binding to galectin-3 was still detectable. Moreover, deoxyfluorination of C2' caused an approximately 8-fold increase in the binding affinity towards galectin-1, whereas binding to galectin-3 was essentially not affected. Lipophilicity measurement revealed that deoxyfluorination at the Gal moiety affects log P very differently compared to deoxyfluorination at the GlcNAc moiety.

The preparation of four per-O-benzyl-d- or l-glycero-d-galacto and d- or l-glycero-d-gluco heptopyranosyl sulfoxides and the influence of their side-chain conformations on reactivity and stereoselectivity in glycosylation reactions are described. The side-chain conformation in these donors is determined by the relative configuration of its point of attachment to the pyranoside ring and the two flanking centers in agreement with a recent model. In the d- and l-glycero-d-galacto glycosyl donors, the d-glycero-d-galacto isomer with the more electron-withdrawing trans,gauche conformation of its side chain was the more equatorially selective isomer. In the d- and l-glycero-d-gluco glycosyl donors, the l-glycero-d-gluco isomer with the least disarming gauche,gauche side-chain conformation was the most equatorially selective donor. Variable temperature NMR studies, while supporting the formation of intermediate glycosyl triflates at -80 °C in all cases, were inconclusive owing to a change in the decomposition mechanism with the change in configuration. It is suggested that the equatorial selectivity of the l-glycero-d-gluco isomer arises from H-bonding between the glycosyl acceptor and O6 of the donor, which is poised to deliver the acceptor antiperiplanar to the glycosyl triflate, resulting in a high degree of SN2 character in the displacement reaction.

Generally applicable and stereoselective formation of 1,2-cis-glycopyranosidic linkage remains a long sought after yet unmet goal in carbohydrate chemistry. This work advances a strategy to this challenge via stereoinversion at the anomeric position of 1,2-trans glycosyl ester donors. This SN2 glycosylation is enabled under gold catalysis by an oxazole-based directing group optimally tethered to a leaving group and achieved under mild catalytic conditions, in mostly excellent yields, and with good to outstanding selectivities. The strategy is also applied to the synthesis of oligosaccharides.

An efficient and simple approach for stereoselective synthesis of β-Kdo C-glycosides was described, which relies on easily available peracetylated anomeric acetate or anomeric 2-pyridyl sulfide to couple with carbonyl compounds via SmI2-mediated Reformatsky reactions. The utility of this methodology is exemplified by the streamlined synthesis of a practical β-Kdo C-glycoside with an anomeric aminopropyl linker to conjugate with other biomolecules for further biological studies.

Metabolic chemical reports have fundamentally changed the way researchers study glycosylation. However, when administered as per-O-acetylated sugars, reporter molecules can participate in nonspecific chemical labeling of cysteine residues termed S-glycosylation. Without detailed proteomic analyses, these labeling events can be indistinguishable from bona fide enzymatic labeling convoluting experimental results. Here, we report a solution in the synthesis and characterization of two reporter molecules functionalized at the anomeric position with hexanoic acid: 1-Hex-GlcNAlk and 1-Hex-6AzGlcNAc. Both reporters exhibit robust labeling over background with negligible amounts of nonspecific chemical labeling in cell lysates. This strategy serves as a template for the design of future reporter molecules allowing for more reliable interpretation of results.

The synthesis of glycosides incorporating basic nitrogen atoms is a longstanding challenge in organic synthesis. By leveraging the reactivity of glycosyl anions, a general method has been developed that enables use of glycosyl donors incorporating unprotected, basic amines.

Selenosugars are interesting targets of organic synthesis as they would possess potential biological activities. However, 4-selenotherofuranose derivatives, which have trans configuration for the two dihydroxy substituents at the 2,3-positions and a glycoside bond at the anomeric position, are not available in the current selenosugar library. In this study, racemic 4-selenothreofuranose derivatives were synthesized from trans-3,4-dioxygenated tetrahydroselenophenes in 77-99% yields with the α/β selectivity about 7:3 via oxidation and subsequent seleno-Pummerer rearrangement. The acetoxy group introduced at the anomeric position was then substituted with various nucleophiles, including activated 6-chloropurine, which afforded 4'-selenothreonucleoside derivatives, in the presence of BF3·OEt2 or TMSOTf. The stereochemistry of the selenosugar products was established by 1H NMR spectroscopy as well as X-ray analysis. The similar α/β selectivity observed in the latter glycosylation reaction to that in the former seleno-Pummerer rearrangement suggested the mediation of a common selenonium intermediate (-Se+=C

Dodecamer duplex DNA containing anomeric (α/β‐d) and enantiomeric (β‐l/β‐d) 2’‐deoxycytidine mismatches was studied with respect to base pair stability in the absence and presence of silver ions. Stable duplexes with silver‐mediated cytosine–cytosine pairs were formed by all anomeric and enantiomeric combinations. Stability changes were observed depending on the composition of the mismatches. Most strikingly, the new silver‐mediated base pair of anomeric α‐d‐dC with enantiomeric β‐l‐dC is superior to the well‐noted β‐d/β‐d‐dC pair in terms of stability. CD spectra were used to follow global helical changes of DNA structure., Set‐in‐the‐silver C: The base pair stability of anomeric (α/β‐d) and enantiomeric (β‐l/β‐d) 2’‐deoxycytidine mispair combinations in duplex DNA was studied in the absence and presence of silver ions. Stable duplexes with Ag+‐mediated cytosine–cytosine pairs were formed by all anomeric and enantiomeric combinations. The Ag+‐mediated base pair of anomeric α‐d‐dC (α‐d‐2’‐deoxycytidine) with enantiomeric β‐l‐dC (β‐l‐2’‐deoxycytidine) is superior to the well‐noted β‐d/β‐d‐dC pair in view of stability and T m increase.

The first system controlled anomeric isomerism of glucopyranoside-functionalized N-heterocyclic carbenes based pyridine enhanced precatalyst preparation, stabilization and initiation type palladium(II) complexes (Glu-NHCs-Pd(II)-PEPPSI, 2a–d) were prepared and fully characterized. It is interesting to note that pure β–anomer PEPPSI complex 2d was obtained, in which the Glu-substituent connects to the imidazole heterocycle ring N through ethoxy bridged anomeric carbon. In addition, the catalytic activities revealed that Glu-NHCs-Pd(II)-PEPPSI complexes 2a-d are efficient catalysts for the aqueous Suzuki reaction. Under optimized conditions, a series of fluorene-cored functional materials with different aryl-substituents were synthesized through the Suzuki reaction with excellent yields. The Glu-NHCs-Pd(II)-PEPPSI complex containing bulky and rigid 2,5-dimethylphenyl group played an important role in maintaining the β conformation and improving the catalytic activity significantly.

Stereoselective reactions at the anomeric carbon constitute the cornerstone of preparative carbohydrate chemistry. Here, we report stereoselective C-arylation and etherification reactions of anomeric trifluoroborates derived from BMIDA esters. These reactions are characterized by high anomeric selectivities for 2-deoxysugars and broad substrate scope (24 examples), including disaccharides and trifluoroborates with free hydroxyl groups. Taken together, this new class of carbohydrate reagents adds the palette of anomeric nucleophile reagents suitable for efficient installation of C-C bonds.

Cerebrosides (n-HexCer) and glycosphingosines (n-HexSph) constitute two sphingolipid subclasses. Both are comprised of a monosaccharide head group (glucose or galactose in mammalian cells) linked via either an alpha- or beta- glycosidic linkage to the sphingoid backbone (n = α or β, depending upon the nature of the linkage to the anomeric carbon of the sugar). Cerebrosides have an additional amide-bonded fatty acyl chain linked to the sphingoid backbone. While differentiating the multiple isomers (i.e., glucose vs. galactose, α- vs. β-linkage) is difficult, it is crucial for understanding their specific biological roles in health and disease states. Shotgun tandem mass spectrometry has been a powerful tool in both lipidomics and glycomics analysis but is often limited in its ability to distinguish isomeric species. This work describes a new strategy combining shotgun tandem mass spectrometry with gas-phase ion chemistry to achieve both differentiation and quantification of isomeric cerebrosides and glycosphingosines. Briefly, deprotonated cerebrosides, [n-HexCer−H](−), or glycosphingosines, [n-HexSph−H](−), are reacted with terpyridine(Terpy)-magnesium complex dications, [Mg(Terpy)(2)](2+) in the gas phase to produce charge-inverted complex cations, [n-HexCer−H+MgTerpy](+), or [n-HexSph−H+MgTerpy](+). The collision-induced dissociation (CID) of the charge-inverted complex cations leads to significant spectral differences between the two groups of isomers, α-GalCer, β-GlcCer, and β-GalCer for cerebrosides, and α-GlcSph, α-GalSph, β-GlcSph, and β-GalSph for glycosphingosines, which allows for isomer distinction. Moreover, we describe a quantification strategy with the normalized %Area extracted from selected diagnostic ions that quantify either three isomeric cerebroside or four isomeric glycosphingosine mixtures. Analytical performance was also evaluated in terms of accuracy, repeatability, and inter-day precision. Furthermore, CID of the product ions resulting from 443 Da loss from the charge-inverted complex cations ([n-HexCer−H+MgTerpy](+)) is performed and demonstrated for localizing the double bond position on the amide-bonded monounsaturated fatty acyl chain in the cerebroside structure. The proposed strategy was successfully applied to the analysis of total cerebroside extracts from the porcine brain providing in-depth structural information of cerebrosides from a biological mixture.

A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3-cis-1,4-trans systems. In the case of electron-rich aromatic nucleophiles, an equilibration occurs at the anomeric center with the selective formation of 1,3-trans-1,4-cis systems. This anomalous result was rationalized through density functional theory calculations. Different oxocarbenium ions such as those derived from dihydroisobenzofuran, pyrrolidine, and oxazolidine heterocycles can also be used as a substrate for the oxo-Re-mediated allylation reaction.

Anthracyclines are effective drugs in the treatment of various cancers, but their use comes with severe side effects. The archetypal anthracycline drug, doxorubicin, displays two molecular modes of action: DNA double-strand break formation (through topoisomerase II alpha poisoning) and chromatin damage (via eviction of histones). These biological activities can be modulated and toxic side effects can be reduced by separating these two modes of action through alteration of the aminoglycoside moiety of doxorubicin. We herein report on the design, synthesis, and evaluation of a coherent set of configurational doxorubicin analogues featuring all possible stereoisomers of the 1,2-amino-alcohol characteristic for the doxorubicin 3-amino-2,3-dideoxyfucoside, each in nonsubstituted and N,N-dimethylated forms. The set of doxorubicin analogues was synthesized using appropriately protected 2,3,6-dideoxy-3-amino glycosyl donors, equipped with an alkynylbenzoate anomeric leaving group, and the doxorubicin aglycon acceptor. The majority of these glycosylations proceeded in a highly stereoselective manner to provide the desired axial alpha-linkage. We show that both stereochemistry of the 3-amine carbon and N-substitution state are critical for anthracycline cytotoxicity and generally improve cellular uptake. N,N-Dimethylepirubicin is identified as the most potent anthracycline that does not induce DNA damage while remaining cytotoxic.

α-2′-De­oxy­cyti­dine is the α-anomeric analogue of the canonical β-2′-de­oxy­cyti­dine and adopts conformational parameters which lie outside the conformational range usually preferred by α-nucleo­sides. Crystal packing is controlled by N—H⋯O and O—H⋯O contacts between the nucleobase and sugar moieties., β-2′-De­oxy­ribo­nucleo­sides are the constituents of nucleic acids, whereas their anomeric α-analogues are rarely found in nature. Moreover, not much infor­mation is available on the structural and conformational parameters of α-2′-de­oxy­ribo­nucleo­sides. This study reports on the single-crystal X-ray structure of α-2′-de­oxy­cyti­dine, C9H13N3O4 (1), and the conformational param­eters characterizing 1 were determined. The conformation at the glycosylic bond is anti, with χ = 173.4 (2)°, and the sugar residue adopts an almost symmetrical C2′-endo-C3′-exo twist (; S-type), with P = 179.7°. Both values lie outside the conformational range usually preferred by α-nucleo­sides. In addition, the amino group at the nucleobase shows partial double-bond character. This is supported by two separated signals for the amino protons in the 1H NMR spectrum, indicating a hindered rotation around the C4—N4 bond and a relatively short C—N bond in the solid state. Crystal packing is controlled by N—H⋯O and O—H⋯O contacts between the nucleobase and sugar moieties. Moreover, two weak C—H⋯N contacts (C1′—H1′ and C3′—H3′A) are observed. A Hirshfeld surface analysis was carried out and the results support the inter­molecular inter­actions observed by the X-ray analysis.

Glycoside hydrolases (GH) cleave carbohydrate glycosidic bonds and play pivotal roles in living organisms and in many industrial processes. Unlike acid-catalyzed hydrolysis of carbohydrates in solution, which can occur either via cyclic or acyclic oxocarbenium-like transition states, it is widely accepted that GH-catalyzed hydrolysis proceeds via a general acid mechanism involving a cyclic oxocarbenium-like transition state with protonation of the glycosidic oxygen. The GH45 subfamily C inverting endoglucanase from Phanerochaete chrysosporium (PcCel45A) defies the classical inverting mechanism as its crystal structure conspicuously lacks a general Asp or Glu base residue. Instead, PcCel45A has an Asn residue, a notoriously weak base in solution, as one of its catalytic residues at position 92. Moreover, unlike other inverting GHs, the relative position of the catalytic residues in PcCel45A impairs the proton abstraction from the nucleophilic water that attacks the anomeric carbon, a key step in the classical mechanism. Here, we investigate the viability of an endocyclic mechanism for PcCel45A using hybrid quantum mechanics/molecular mechanics (QM/MM) simulations, with the QM region treated with the self-consistent-charge density-functional tight-binding level of theory. In this mechanism, an acyclic oxocarbenium-like transition state is stabilized leading to the opening of the glucopyranose ring and formation of an unstable acyclic hemiacetal that can be readily decomposed into hydrolysis product. In silico characterization of the Michaelis complex shows that PcCel45A significantly restrains the sugar ring to the 4C1 chair conformation at the −1 subsite of the substrate binding cleft, in contrast to the classical exocyclic mechanism in which ring puckering is critical. We also show that PcCel45A provides an environment where the catalytic Asn92 residue in its standard amide form participates in a cooperative hydrogen bond network resulting in its increased nucleophilicity due to an increased negative charge on the oxygen atom. Our results for PcCel45A suggest that carbohydrate hydrolysis catalyzed by GHs may take an alternative route from the classical mechanism.

Herein, a new magnetic metal–organic frameworks based on Fe3O4 (NMMOFs) with porous and high surface area materials were synthesized. Then, NMMOFs were characterized by FT-IR, XRD, SEM, elemental mapping, energy dispersive X-ray (EDS), TG, DTG, VSM, and N2 adsorption–desorption isotherms (BET). Fe3O4@Co(BDC)-NH2 as a magnetic porous catalyst was applied for synthesis of novel fused pyridines and 1,4-dihydropyridines with pyrazole and pyrimidine moieties as suitable drug candidates under ultrasonic irradiation. The significant advantages of the presented methodology are mild, facile workup, high yields, short reaction times, high thermal stability, and reusability of the described NMMOFs catalyst.

Selective modification of the hydroxyl groups of sugars has been a long-standing challenge due to their proximate relative reactivity. Herein, we report a TMSOTf-catalyzed selective acetylation of the non-anomeric hydroxyl groups of several per-O-TMS-protected sugar substrates while leaving their anomeric group unaffected. In addition to standing versatile by itself, the anomeric O-TMS group left intact can be functionalized to afford key sugar precursors such as imidate donors, which could otherwise be synthesized via a stepwise anomeric deprotection-functionalization procedure.

L‐Hexoses are rare but biologically significant components of various important biomolecules, however, most are prohibitively expensive if commercially available, limiting their study and biotechnological exploitation. New, efficient methods to access L‐hexoses and their derivatives are thus of great interest. In a previous study, we showcased a stereoselective Bu 3 SnH‐mediated transformation of a 5‐ C ‐bromo‐D‐glucuronide to an L‐iduronide. We have now drawn inspiration from this result to derive a new methodology which can be harnessed to access other L‐hexoses. DFT calculations demonstrate that a combination of a β‐F at the anomeric position and a methoxycarbonyl substituent at C‐5 is key to optimising the selectivity for the L‐hexose product. Our investigations have also culminated in the development of the shortest known synthetic route to a derivative of L‐idose from commercially available starting material (45% yield over 3 steps). Collectively, these results address the profound lack of understanding about how to synthesise L‐hexoses in a stereoselective fashion.

In this work, we have developed a new approach for the synthesis of fluoroglycoside analogues. This strategy used a simple alkylation protocol and allowed the installation of a simple aglyconic alkane with the s configuration. Moreover, the glycosylation of fluorinated glucoside analogues with 4'-demethylepipodophyllotoxin furnished novel fluoroetoposide analogues. In these cases, the α anomers were formed as major products with an S configuration at the C-4 of the aglycone.

Herein, we reported the stereodivergent synthesis of C-glycosamino acids via Pd/Cu dual catalysis and found a suitable system to resolve many challenges, such as the tolerance towards the density of functional groups, the variability of the anomeric position, the compatibility of appropriate catalyst combinations, the regioselectivity of nucleophiles, and the match/mismatch problems between chiral substrates and chiral ligand-metal complexes. The method enables the efficient preparation of a series of unnatural C-glycosamino acid skeletons bearing two contiguous stereogenic centers in good yields with excellent diastereos-electivity. From this crucial precursor, various C-glycosamino acid derivatives have been achieved diversely. The readily prepared C-glycosamino acid hybrids will meet the growing demands for the development of new molecular entities for discovering new drugs and materials. This stereodivergent synthesis of C-glycosamino acids will further accelerate the study of their structural features, mode of action, and potential biological applications in the near future.

The introduction of glycosides bearing basic nitrogen is challenging using conventional Lewis acid-promoted pathways owing to competitive coordination of the amine to the Lewis acid promoter. Additionally, because many aminoglycosides lack a C2 substituent, diastereomeric mixtures of O-glycosides often produced. Herein, we present a method for synthesis of α- or β−2,3,6-trideoxy-3-aminoglycosides and 2,4,6-trideoxy-4-amino O-glycosides from a common precursor. Our strategy proceeds by the reductive lithiation of thiophenyl glycoside donors and trapping of the resulting anomeric anions with 2-methyltetrahydropyranyl (MTHP) peroxides. We apply this strategy to the synthesis of α- and β-forosamine, pyrrolosamine, acosamine, and ristosamine derivatives using primary and secondary peroxides as electrophiles. α-Linked products are obtained in 60–96% yield and with >50:1 selectivity. β-Linked products are obtained in 45–94% yield and with 1.7–>50:1 stereoselectivity. Contrary to donors bearing an equatorial amine substituent, donors bearing an axial amine substituent favored β-products at low temperatures. This work establishes a general strategy to synthesize O-glycosides bearing a basic nitrogen.

Generally, glycosylation reactions activate an anomeric substituent in a glycosyl donor to generate an oxocarbenium ion intermediate. Here we report a novel glycosylation reaction triggered by the activation of a 2-O-substituted propargyl group in a 3,6-O-1,1′-[(ethane-1,2-diyl)bibenzene-2,2′-bis(methylene)]-β-thioglucoside. This reaction proceeds through a cationic Au(I)-mediated intramolecular migration of the anomeric substituent onto the alkyne moiety of the propargyl group, followed by α-attack by the hydroxy group in the glycosyl acceptor on the oxocarbenium ion. The migration of the anomeric group occurs selectively through a 6-exo-dig pathway. The 2-(phenylsulfanyl)prop-2-en-1-yl group produced during the glycosylation is removable under conditions similar to those used for removing an allyl group. This reaction will be developed for further applications in orthogonal oligosaccharide synthesis.

2-Amino-3-cyanopyridine derivatives were synthesized in an ultrasonic bath and one pot four-component reactions with high yields, in a short time, without solvent and catalyst, and anticancer activ...

Herein we present the direct asymmetric synthesis of tetrazole-functionalized 1-deoxynojirimycin derivatives from simple sugars via a Schwartz’s reagent-mediated reductive amide functionalization followed by a variant of the Ugi-azide multi-component reaction. The anomeric configurations of two products were unambiguously confirmed by X-ray analysis. This work also describes examples of interesting further transformations of the title products. Finally, some surprising observations regarding the mechanism of their formation were made.

In the current study, a novel acidic ionic liquid catalyst based on 8-hydroxyquinoline, namely 8,8′,8″-([1,3,5-triazine-2,4,6-triyl]tris[oxy])tris(1-sulfoquinolin-1-ium)chloride (TTS), was designed and synthesized. The structure of the prepared acidic ionic liquid (AIL) was fully investigated by using Fourier transform infrared (FT-IR) spectroscopy, energy dispersive X-ray (EDX) analysis, thermogravimetric analysis/differential thermal analysis (TGA/DTA), 1HNMR, 13CNMR and mass spectroscopy. Then, the catalytic performance of described AIL was successfully inspected toward the four-component synthesis of pyridine derivatives via a cooperative vinylogous anomeric-based oxidation. Novel AIL (TTS) showed a very high efficiency in the synthesis of pyridines.

In an effort to discover new imidazolyl nucleus belonging to the family of N-fused heterocyclic compounds which display broad spectrum of biological applications, a series of novel imidazolyl pyrazolopyridines 3a,b–7a,b and imidazolyl pyrazoloquinoxaline 8a–d were synthesized. The structures of all the synthesized compounds were confirmed using spectroscopic data and elemental analyses. The compounds were synthesized using conventional heating besides the environmentally friendly benign techniques and reagents as microwave technique and catalyst under solvent–free conditions and short reaction times by anomeric-based oxidation (ABO) to the products in the final step of the synthetic pathway. Further all the synthesized bioactive molecules are tested for their biological potency: in vitro antimicrobial activity using a disc diffusion technique was performed against various Gram-positive and Gram-negative bacteria as well as fungal strains using Chloramophenicol and Fluconazole as positive controls. Free radical scavenging activity has been investigated using the DPPH scavenging methods. Interestingly, most of the synthesized compounds exhibited good to excellent antibacterial activities against most of bacterial strains and showed the highest antioxidant activity.

The disulfide bond plays an important role in the formation and stabilisation of higher order structures of peptides and proteins, while in recent years interest in this functional group has been extended to carbohydrate chemistry. Rarely found in nature, glycosyl disulfides have attracted significant attention as glycomimetics, with wide biological applications including lectin binding, as key components of dynamic libraries to study carbohydrate structures, the study of metabolic and enzymatic studies, and even as potential drug molecules. This interest has been accompanied and fuelled by the continuous development of new methods to construct the disulfide bond at the anomeric centre. Glycosyl disulfides have also been exploited as versatile intermediates in carbohydrate synthesis, particularly as glycosyl donors. This review focuses on the importance of the disulfide bond in glycobiology and in chemistry, evaluating the different methods available to synthesise glycosyl disulfides. Furthermore, we review the role of glycosyl disulfides as intermediates and/or glycosyl donors for the synthesis of neoglycoproteins and oligosaccharides, before finally considering examples of how this important class of carbohydrates have made an impact in biological and therapeutic contexts.

As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared from N-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and stereoselectivity. α-Anomers were accessed via reagent control by utilising additive CH3CN and TBAI, whereas the β-anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known sialidases, and potential detection and investigation of novel sialidases.