4-Methoxyphenyl (MP) aglycone has been widely used as an anomeric protective group (orthogonal to many other frequently used protective groups) during syntheses of various oligosaccharides. We studied the cleavage of the methyl group in MP aglycone under acidic and basic conditions and found that under optimized conditions (EtSH, NaOH, N-methylpyrrolidone, 130 °C) the target glycosides (either protected or unprotected) with 4-hydroxyphenyl (HP) aglycone can be prepared in preparative yields approaching ∼90 % for (partially) protected HP glycosides and ∼80 % for unprotected HP glycosides. Subsequent substitution of the phenolic hydroxy group in the obtained HP glycosides with various alkylating agents efficiently gave the corresponding glycosides with various functional groups in aglycone. The results obtained suggest that the MP aglycone can be considered as a cleavable pre-spacer aglycone, thereby expanding the family of Janus aglycones.

Catechin, proanthocyanidin B-2, epiafzelechin-(4β→8)-epicatechin, dihydroquercetin, and eriodictyol were isolated via the extraction from the knot wood of plum Renclode blue (Prunus domestica “Renklod sinii”) and subsequent HPLC. Structures of these compounds were confirmed using 2D NMR spectroscopy and mass spectrometry.

Aromatic-substituted isoselenocyanates were reacted with sodium azide to yield novel sodium salts of phenyltetrazol-5-selenones, alongside analogous phenyltetrazol-5-thione derivatives for comparison. These compounds were fully characterized using single-crystal X-ray diffraction, NMR spectroscopy, IR/Raman spectroscopy, and high-resolution mass spectrometry. Surprisingly, X-ray crystallography revealed an unconventional coordination mode, with the sodium cation binding to the tetrazole nitrogen atoms rather than the selenium or sulfur centers, while preserving the C=Se/S double bonds. The electronic structure and delocalization effects were explored using DFT calculations, aromaticity criteria (EDDB and GIMIC), and vibrational spectroscopy in both solid and solution states. Hydrogen bonding studies demonstrated that nitrogen and chalcogen atoms in 2a and 5a interact with water, with S(Se)& sdot;& sdot;& sdot;HO bonds being significantly weaker than N & sdot;& sdot;& sdot;HO-consistent with the observed chalcogen-directed alkylation at Se/S centers. Additionally, the influence of deuterated solvents and temperature on (Herr, 2002)13 & Scy;-77Se bond NMR parameters was established. This comprehensive study offers novel insights into the coordination chemistry and reactivity of tetrazole-based chalcogen derivatives, while also elucidating their structural and electronic properties.

Objective: Synthetic lipophilic constructs (Function–Spacer–Lipids, FSLs) are excellent tools for modification of cell surface with almost any molecular fragment. The aim of this research is synthesis of FSLs containing both glycan and fluorescent tag introduced in the structure of the construct independently to each other. Such compounds allow to avoid treatment with fluorescently labeled antibodies prior to visualization of inserted glycans by confocal microscopy thus opening the wide range of possibilities for studying biological processes involving these glycans. Methods: Two FSLs containing same glycan, A (type 2) tetrasaccharide, and spacerlipid block, CMG (carboxymethylglycine) spacer-arm and DOPE (dioleoylphosphatidylethanolamine) lipid, and various fluorescent tags, fluoresceine and sulfo-Cyanine-3, were synthesized. Derivatives of α- or ε-azido lysine were used as central blocks, to which all other fragments were attached. Two various approaches differing in the order of introduction of components were employed. Conjugation via CuAAC reaction was used in both synthetic schemes. Results and Discussion: The first approach (the following order of attachment of components: glycan, then spacer-lipid, then fluorescent tag) allowed to obtain target FSL according to proposed synthetic plan. When the second approach was employed (the following order of attachment: fluorescent tag, then glycan, then spacer–lipid), side reaction of racemization of central lysine block was observed during conjugation of glycan part. To overcome this problem, synthetic sequence was changed: amino group in lysine unit was protected and glycan was introduced prior to fluorescent tag. This modification allowed to avoid undesired racemization. Conclusions: Two FSL constructs containing A (type 2) tetrasaccharide, CMG–DOPE spacer-lipid block, and fluorescent tag (fluoresceine or sulfo-Cyanine-3) were obtained. Independent manner of attachment of glycan and fluorophore allows to study interaction of glycan with carbohydrate binding proteins directly in the cell membrane.

ABSTRACT The new type of the four‐component tandem Knoevenagel–Michael reaction was discovered: the transformation of arylaldehydes, N , N′ ‐dimethylbarbituric acid, malononitrile, and morpholine in alcohols and other organic solvents without any other additives at ambient temperature resulted in the selective formation of a new substituted unsymmetrical ionic scaffold with two pharmacology‐active heterocyclic rings. This new four‐component reaction is a simple and efficient route to a previously unknown substituted ionic unsymmetrical scaffold containing N , N′ ‐dimethylbarbituric acid and morpholine. These ionic scaffolds are promising for various biomedical applications, for example, as anticonvulsants and anti‐inflammatory drugs, as well as anti‐AIDS agents. In this research, we also accomplished the efficient cyclization of morpholin‐4‐ium 5‐(2,2‐dicya‐no‐1‐arylethyl)‐1,3‐dimethyl‐2,6‐di‐oxo‐1,2,3,6‐tetrahydro‐pyrimidin‐4‐olates by the action of NBS–NaOAc system, with the formation of 5,7‐dimethyl‐4,6,8‐trioxo‐2‐aryl‐5,7‐diazaspiro[2.5]octane‐1,1‐dicarbonitriles in 83%–98% yields. In the final stage of our research, direct one‐pot multicomponent transformation of benzaldehydes, N , N′ ‐dimethylbarbituric acid, and malononitrile into spirobarbituric cyclopropanes was accomplished in 75%–97% yields. The spiro‐barbituric cyclopropanes are potentially active as remedies against various inflammatory, infectious, immunological, or malignant diseases.

Glycosyl halides are historically one of the first glycosyl donors used in glycosylation reactions, and interest in glycosylation reactions involving this class of glycosyl donors is currently increasing. New methods for their activation have been proposed and effective syntheses of oligosaccharides with their participation have been developed. At the same time, the possibilities of using these approaches to the synthesis of sialosides are restricted by the limited diversity of known sialyl halides (previously, mainly sialyl chlorides, less often sialyl bromides and sialyl fluorides, with acetyl (Ac) groups at the oxygen atoms and AcNH, Ac2N and N3 groups at C-5 were used). This work describes the synthesis of six new N-acetyl- and N-trifluoroacetyl-sialyl chlorides and bromides with O-chloroacetyl and O-trifluoroacetyl protective groups. Preparation of N,O-trifluoroacetyl protected derivatives was made possible due to development of the synthesis of sialic acid methyl ester pentaol with N-trifluoroacetyl group.

The rapid increase in the antibiotic resistance of microorganisms, capable of causing diseases in humans as destroying cultural heritage sites, is a great challenge for modern science. In this regard, it is necessary to develop fundamentally novel and highly active compounds. In this study, a series of N4-alkylcytidines, including 5- and 6-methylcytidine derivatives, with extended alkyl substituents, were obtained in order to develop a new generation of antibacterial and antifungal biocides based on nucleoside derivatives. It has been shown that N4-alkyl 5- or 6-methylcytidines effectively inhibit the growth of molds, isolated from the paintings in the halls of the Ancient Russian Paintings of the State Tretyakov Gallery, Russia, Moscow. The novel compounds showed activity similar to antiseptics commonly used to protect works of art, such as benzalkonium chloride, to which a number of microorganisms have acquired resistance. It was also shown that the activity of N4-alkylcytidines is comparable to that of some antibiotics used in medicine to fight Gram-positive bacteria, including resistant strains of Staphylococcus aureus and Mycobacterium smegmatis. N4-dodecyl-5- and 6-methylcytidines turned out to be the best. This compound seems promising for expanding the palette of antiseptics used in painting, since quite often the destruction of painting materials is caused by joint fungi and bacteria infection.

Comparison of the reactivity of sialyl chlorides and bromides based on N-acetylneuraminic acid (Neu5Ac) and its deaminated analogue (KDN) in reactions with MeOH and i-PrOH without a promoter revealed that the acetoxy group at C-5 in a molecule of a sialic acid glycosyl donor can destabilize the corresponding glycosyl cation making the SN1-like reaction pathway unfavorable. A change to the SN2-like reaction pathway ensures preferential formation of the α-glycoside.

A total chemical synthesis of spacer-armed Forssman pentasaccharide is reported. The choice of the 2(donor) + 3(acceptor) block scheme, the optimal combination of a limited number of simple protecting groups and the sequence of deprotection steps allowed to achieve the high yield and stereoselectivity of glycosylation and to avoid losses during deprotection. The target pentasaccharide was obtained in a 10-mg scale. 1H and 13C NMR spectra of the Forssman pentasaccharide were completely assigned with the use of various 2D-NMR experiments.

The new type of four-component tandem Knoevenagel- Michael reaction was found: isatins, barbituric acids, malononitrile and morpholine at ambient temperature and without catalysts selectively form new non-symmetrical ionic scaffold, namely, morpholin-4-ium 5-(3-dicyanomethyl2- oxoindolin- 3-yl)- 1,3-dimethyl-2, 6-dioxo-1, 2, 3, 6-tetrahydropyrimidin-4-olate derivatives, in 80-98% yields. Their structure was confirmed using 2D NMR such as 1 H- 1 H COSY, 1 H- 13 C HSQC, and1H-13C HMBC correlation experiments. The products seem promising as they contain three different pharmacologically active heterocyclic rings.

Acinetobacter baumannii is a leading cause of multidrug-resistant bacterial infections worldwide, and the capsular polysaccharide (CPS) is a major virulence determinant. A previous study of A. baumannii from intubated and asymptomatic patients admitted to the intensive care unit (ICU) at the Hospital for Tropical Diseases in Ho Chi Minh City in Vietnam revealed multiple lineages with diverse antibiotic resistance profiles and CPS biosynthesis loci. Here, we show that 48_n, an asymptomatic nasal carriage isolate belonging to ST142, is extensively antibiotic resistant and carries acquired resistance determinants accounting for the resistance profile. 48_n carries the novel KL71 CPS biosynthesis locus in the chromosome. The structure of the CPS produced by 48_n was established using 1H and 13C nuclear magnetic resonance spectroscopy, including two-dimensional 1Н,1Н COSY, 1Н,1Н TOCSY, 1Н,1Н ROESY, 1Н,13C HSQC, and 1Н,13C HMBC experiments, and confirmed by Smith degradation. Consistent with the genetic content of KL71, the K71 CPS was found to be made up of octasaccharide K units containing six l-rhamnose residues and one residue each of N-acetyl-d-glucosamine and d-glucuronic acid. K71 CPS was branched and closely related to the K74 CPS produced by BAL_309, an antibiotic susceptible ST142 isolate recovered from an intubated patient in the same ICU 7 years later. K71 and K74 differ only in the linkage between K units, and this is due to the replacement of a single gene at the K locus that codes for the Wzy polymerase. IMPORTANCE:The majority of Acinetobacter baumannii genomes sequenced and analyzed to develop an understanding of extensively drug-resistant (XDR) isolates belong to the globally disseminated CC2 clonal complex. While XDR isolates belonging to rarer lineages are often unexplored, detailed analyses could provide novel insights into the spread of resistance, as well as cell surface features such as the CPS that determine the specificity of non-antibiotic therapeutics required to treat XDR infections that resist antimicrobial chemotherapy. Here, we describe the properties of an XDR asymptomatic nasal carriage isolate recovered in Vietnam that belongs to ST142, a rarely encountered sequence type. We report the resistance profile and correlate this with detected resistance determinants. We also solve the structure of the CPS and reveal its relationship with CPS produced by other A. baumannii isolates.

Glycosphingolipids (GSL) are functionally important components of the cell membrane and recognition of their glycan "head" by the immune system is a key part of normal and pathological processes. Recognition of glycolipid antigens on a living cell, their structure, "context" (microenvironment and clustering), presentation including orientation and distance from the plasma membrane, as well as molecular dynamics are important. GSL antigens are targets for the development of anticancer vaccines and therapeutic antibodies, therefore, control of the presentation of their glycans by synthetic methods opens up new possibilities in medicine. In this work, we synthesized 13 GSL analogues as function-spacer-lipids (FSLs) with the same head (blood group A tetrasaccharide, ABO system) but each either differing in the structure of the lipid tail, or the length of the region between the head and the tail, or cluster organization of the head (from 2 to 4 tetrasaccharides in a cluster). The insertion of these FSLs into an artificial and erythrocyte membranes was compared, and their interaction with antibodies was studied, including erythrocyte agglutination. The results give further insight into knowledge of the membrane presentation of GSLs (some results can be extrapolated to glycoproteins) and factors involved in their interaction with antibodies.

Coupling between 2-pyridylselenyl chloride and various cyanopyridinium salts resulted in the formation of dicationic pyridinium-fused 1,2,4-selenodiazoles. Novel bicyclic heterocycles are highly soluble in water and readily precipitate pertechnetate and perrhenate anions from aqueous media. All the novel compounds were comprehensively characterized using 1H and 13C NMR techniques, ESI-MS, and X-ray diffraction analysis (for eight compounds). Theoretical calculations have shown the intricate nature of chalcogen bonding (ChBs) and anion-pi interactions across a series of compounds, each exhibiting unique bonding patterns and interaction energies. Compounds [1]H(ReO4)2, [2]H(ReO4)2, [3](ReO4), [2]H(TcO4)2 and [3](TcO4) displayed complex assemblies, highlighting the role of ion -pair interactions, bifurcated ChBs, and directional mater bonds.

Synthetic analogs of glycolipids are widely used for modification of the cell membrane with glycans. Constructs capable of selective (or even specific) insertion into membrane rafts are of special interest because various molecules (transmembrane proteins, their cofactors, and glycosphingolipids) essential for cellular processes are concentrated in these domains. A suitable lipid part for such constructs is a cholesterol derivative that retain the ability of the 3β-substituent to form the hydrogen bonds in the plasma membrane. Herein, synthesis of lipophilic construct containing 3β-cholesterylamine as a lipid part and blood group A (type 2) tetrasaccharide as a glycan part is described.

Stereocontrolled 1,2-trans-alpha-arabinofuranosylation trans-alpha-arabinofuranosylation using polysilylated mono- and disaccharide glycosyl donors was investigated. A complete alpha-stereoselectivity of 1,2-trans-arabinofuranosylation trans-arabinofuranosylation was found for Ara-beta-(1 -> 2)- Ara disaccharide glycosyl donors containing five triisopropylsilyl (TIPS) groups with arylthiol (1) 1 ) (as shown in our previous publications) or N-phenyltrifluoroacetimidoyl (2) 2 ) (this work) leaving groups. Conversely, in case of monosaccharide thioglycosides polysilylated with acyclic silyl groups (TIPS, TBDPS), stereoselectivity of glycosylation was lower (alpha:beta = 7-8:1), although the desired alpha-isomer still dominated. Disaccharide glycosyl donor 2 was successfully used in the synthesis of linear alpha-(1 -> 5)-, beta-(1 -> 2)-linked hexaarabinofuranoside useful for further preparation of conjugates thereof as antigens valuable for the diagnosis of mycobacterioses.

An ability of glycolipids to embed membrane of living cells opens an opportunity to modify cellular surface via insertion of synthetic lipophilic constructs carrying given glycan (or any other molecular fragment). Detection of thus inserted glycans by fluorescent microscopy requires treatment with corresponding fluorescently labeled antibodies. Di- (IgG) and decavalent (IgM) antibodies can significantly affect the distribution of glycolipids in the membrane, therefore direct visualization of embedded lipophilic constructs is required. To achieve this, fluorescent tag must be included in the composition of the lipophilic constructs and at the same time be located at a sufficient distance from glycan part. Here we propose two approaches to the synthesis of these compounds and describe obtaining of two constructs carrying A (type 2) tetrasaccharide and either fluorescein or sulfo-cyanine-3.

Acinetobacter baumannii is a critical priority nosocomial pathogen that produces a variety of capsular polysaccharides (CPSs), the primary receptors for specific depolymerase-carrying phages. In this study, the tailspike depolymerases (TSDs) encoded in genomes of six novel Friunaviruses, APK09, APK14, APK16, APK86, APK127v, APK128, and one previously described Friunavirus phage, APK37.1, were characterized. For all TSDs, the mechanism of specific cleavage of corresponding A. baumannii capsular polysaccharides (CPSs) was established. The structures of oligosaccharide fragments derived from K9, K14, K16, K37/K3-v1, K86, K127, and K128 CPSs degradation by the recombinant depolymerases have been determined. The crystal structures of three of the studied TSDs were obtained. A significant reduction in mortality of Galleria mellonella larvae infected with A. baumannii of K9 capsular type was shown in the example of recombinant TSD APK09_gp48. The data obtained will provide a better understanding of the interaction of phage–bacterial host systems and will contribute to the formation of principles of rational usage of lytic phages and phage-derived enzymes as antibacterial agents.

A variety of ribo-, 2′-deoxyribo-, and 5′-norcarbocyclic derivatives of the 8-aza-7-deazahypoxanthine fleximer scaffolds were designed, synthesized, and screened for antibacterial activity. Both chemical and chemoenzymatic methods of synthesis for the 8-aza-7-deazainosine fleximers were compared. In the case of the 8-aza-7-deazahypoxanthine fleximer, the transglycosylation reaction proceeded with the formation of side products. In the case of the protected fleximer base, 1-(4-benzyloxypyrimidin-5-yl)pyrazole, the reaction proceeded selectively with formation of only one product. However, both synthetic routes to realize the fleximer ribonucleoside (3) worked with equal efficiency. The new compounds, as well as some 8-aza-7-deazapurine nucleosides synthesized previously, were studied against Gram-positive and Gram-negative bacteria and M. tuberculosis. It was shown that 1-(β-D-ribofuranosyl)-4-(2-aminopyridin-3-yl)pyrazole (19) and 1-(2′,3′,4′-trihydroxycyclopent-1′-yl)-4-(pyrimidin-4(3H)-on-5-yl)pyrazole (9) were able to inhibit the growth of M. smegmatis mc2 155 by 99% at concentrations (MIC99) of 50 and 13 µg/mL, respectively. Antimycobacterial activities were revealed for 4-(4-aminopyridin-3-yl)-1H-pyrazol (10) and 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-4-(4-benzyloxypyrimidin-5-yl)pyrazole (6). At concentrations (MIC99) of 40 and 20 µg/mL, respectively, the compounds resulted in 99% inhibition of M. tuberculosis growth.

The reaction of aromatic ring-substituted isoselenocyanates with 2-thiopheacetic and 4-pyridinecarboxylic acid hydrazides yielded selenosemicarbazides which were further converted into previously unknown 1,2,4-triazole-3-selones and 3,3'-di(4H-1, 2,4-triazolyl)diselenides. The structures of the obtained compounds were studied by NMR spectroscopy, IR spectroscopy, and high-resolution mass spectroscopy (HR-MS). The bactericidal and fungicidal activity of some obtained compounds was evaluated in molecular modeling studies such as docking and simulation studies. The compound 3ba was reported as the most promising compound to show robust binding energy with different antibacterial and antifungal compounds. The compounds were observed in strong hydrophilic and hydrophobic interactions and remained in stable binding conformation with the receptor enzymes. Furthermore, the interatomic interaction energies were dominated by Van der Waals and electrostatic energies indicating the formation of stable complexes.