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Here, we demonstrate the concerted inhibition of different influenza A virus (IAV) strains using a low-molecular-weight dual-action linear polymer. The 6'-sialyllactose and zanamivir conjugates of linear polyglycerol are optimized for simultaneous targeting of hemagglutinin and neuraminidase on the IAV surface. Independent of IAV subtypes, hemagglutination inhibition data suggest better adsorption of the heteromultivalent polymer than homomultivalent analogs onto the virus surface. Cryo-TEM images imply heteromultivalent compound-mediated virus aggregation. The optimized polymeric nanomaterial inhibits >99.9% propagation of various IAV strains 24 h postinfection in vitro at low nM concentrations and is up to 10000× more effective than the commercial zanamivir drug. In a human lung ex vivo multicyclic infection setup, the heteromultivalent polymer outperforms the commercial drug zanamivir and homomultivalent analogs or their physical mixtures. This study authenticates the translational potential of the dual-action targeting approach using small polymers for broad and high antiviral efficacy.

C-2-Formyl glycals have sustained interest in carbohydrate chemistry as they afford valuable chiral building blocks for many biological-, pharmaceutical-, and industrial-based important molecules. Basically, C-2-formyl glycals are a class of carbohydrates incorporating an α,β-unsaturated aldehyde. Therefore in many organic reactions, the C-2-formyl glycals can serve as an α,β-unsaturated aldehyde core. In this review, we have compiled a literature survey covering the period 2013–2022, on the synthesis of C-2-formyl glycals and further discuss their importance for the synthesis of many medicinal, supramolecular, biological, organic, and material chemistry based molecules.1 Introduction2 Synthesis of C-2-Formyl Glycals2.1 Vilsmeier–Haack Formylation2.2 By Consecutive Cyclization2.3 XtalFluor‑E Based Synthesis3 Applications of C-2-Formyl Glycals3.1 C-2-Formyl Glycals as a Synthons3.2 Anticancer3.3 Anti-inflammatory3.4 Antimicrobial3.5 Glycosidase Inhibitors3.6 Miscellaneous4 Conclusion and Future Aspects

In the last decades, various efforts have been made to synthesize optimal glycotripods for targeting trimeric glycoproteins like asialoglycoprotein receptor, hemagglutinin, and langerin. All these trimeric glycoproteins have sugar binding pockets which are highly selective for a particular carbohydrate ligand. Optimized glycotripods are high affinity binders and have been used for delivering drugs or even applied as drug candidates. The selection of the tripodal base scaffold together with the length and flexibility of the linker between the scaffold and sugar residue, as important design parameters are discussed in this review.

Hyperkalemia is a life-threatening emergency, but it needs to be differentiated from pseudohyperkalemia to avoid unnecessary treatment. We present a case of pseudohyperkalemia in a chronic lymphocytic leukemia patient with severe leukocytosis, highlighting the role of point-of-care potassium. Laboratory workup showed persistent hyperkalemia on analysis of venous blood samples even after treatment for hyperkalemia. Point-of-care potassium checks on whole arterial blood immediately after sampling were consistently in the normal range. Treatments for hyperkalemia were stopped to avoid life-threatening hypokalemia.

We have developed an efficient methodology for the synthesis of (2R,3S,4R)-2-hydroxymethyl-3,4-dihydroxy-6-aryl-7-aroylchromanes in which the chirality at the C-2, C-3, and C-4 positions is being drawn from C-glucopyranosyl aldehyde, which in turn can be efficiently synthesized from d-glucose. Thus, the synthesis starts with the transformation of sugar aldehyde into 1-(E-1-arylpropenon-3-yl)-3,4,6-tri-O-benzyl-d-glucals using Claisen-Schmidt type condensation reaction with different acetophenones and then to 1,2-disubstituted glucals via Pd(II)-catalyzed cross dehydrogenative coupling reaction, which in turn has been efficiently converted into (2R,3S,4R)-chromanes via 6π-electrocyclization and in situ dehydrogenative aromatization.

A route to synthesize 1,2-disubstituted glucals has been developed, which were further converted to substituted chromanes by thermal 6π-electrocyclization in HMPA followed by in situ aromatization. One of the key steps in the synthesis of chromane is metal-free generation of C1-substituted glucal from d-mannose, which was further converted to 1,2-disubstituted glucals by Pd-catalyzed Fujiwara-Moritani reaction with styrenes, acrylates, acrylamide, acrylonitrile, and ethyl vinyl ketone in good yields.

Two sugar PEG-based amphiphilic copolymers have been synthesized by Novozym®-435-catalyzed greener solvent free transesterification reaction of diastereomeric 2,6-anhydro-3,4,5-tri-O-benzyl-glucoheptitol and 2,6-anhydro-3,4,5-tri-O-benzyl-mannoheptitol with PEG-1000 diethyl ester in 80 and 76% yields, respectively. It has been observed that the configurational change at one of the carbons of diastereomeric 2,6-anhydro-heptitols has significant bearing on the degree of polymerization and characteristics of the synthesized polymers. Thus, the study of physico-chemical characteristics of synthesized anhydroglucoheptitol- and anhydromannoheptitol-PEG copolymers revealed that their aqueous solution forms spherical micelles of hydrodynamic diameters 11.2 and 6.4 nm, respectively. Micelles derived from both the amphiphilic copolymers have the potential to solubilize the hydrophobic dye, Nile red. Furthermore, a fluorescence microscopy study revealed that Nile red encapsulated micelles of synthesized amphiphilic copolymers uniformly internalized in A549 cells and thus can be used as a cargo carrier in biological systems. The viability of A549 cells was found to be very high even at a concentration of 500 μg mL−1 of copolymer indicating that they are cyto-compatible.

A simple and convenient methodology has been developed for the synthesis of novel hexopyranosyl pyrimidine homonucleosides and hexopyranosyl double-headed pyrimidine homonucleosides from the corresponding native sugars, d-glucose and d-mannose. Thus, hexose sugars were converted to 2,6-anhydro-3,4,5,7-tetra-O-benzyl-heptitols and 2,6-anhydro-3,4,5-tri-O-benzyl-heptitols by recently developed procedure of Khatri et al. Further, mono- and di-hydroxy 2,6-anhydro-heptitols were converted to their corresponding mono- and di-tosylated derivatives, which were then translated into hexopyranosyl homonucleosides and double-headed homonucleosides by reaction with uracil and thymine in 40–50 and 27–73% overall yields from tetra- and tri-O-benzylated anhydro-heptitols.

Nine 3-[(1-β-D-ribofuranosyl- and 3-[(1-β-D-glucopyranosyl-1H-1,2,3-triazol-4-yl)methylamino]ket-2-en-1-ones have been synthesized by copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction between propargylamine derivatives and 1-azido-2,3,5-tri-O-benzoylβ-D-ribofuranose or 2,3,4,6-tetra-O-acetyl-1-azido-β-D-glucopyranose, followed by deprotection of the resulting tri-O-benzoyl- or tetraO-acetyl-1-β-D-glycosyltriazoles in good yields. The precursor propargylamine derivatives were synthesized by Sonogashira reaction of substituted acetylenes and benzoyl chloride followed by Michael-type addition of propargylamine to the resulting substituted alkynes in good yields. The precursor azido sugars, 1-azido-2,3,5-tri-O-benzoyl-β-D-ribofuranose and 2,3,4,6-tetra-O-acetyl-1-azido-β-D-glucopyranose, were synthesized by azidation of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose and β-D-glucopyranose pentacetate, respectively, with azidotrimethylsilane in the presence of tin(IV) chloride. All products were unambiguously characterized on the basis of the spectral data analysis.

A facile access to C-4′-spiro-oxetano-xylofuranosyl nucleosides has been demonstrated for the first time through Lipozyme® TL IM-mediated regioselective acetylation of one of the primary hydroxyl group over the other primary and secondary hydroxyl groups in 3′-O-benzyl-4′-C-hydroxymethyl-β-D-xylofuranosyl nucleosides. Attempts to optimize a convergent route for these spironucleosides via selective manipulation of hydroxyl groups in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose were unsuccessful. Nevertheless; the present linear biocatalytic route efficiently afforded the C-4′-spiro-oxetanoxylofuranosyl nucleosides T and U in 47 and 38% overall yields, respectively, starting from corresponding furanose diol.

Amphiphilic polymeric nanocarriers have attained immense attention for transporting drugs and other bioactive species to the living systems owing to their high loading capacity and efficient internalization. To avoid the side-effects of undesired interactions within the biological system, the use of biocompatible building blocks is most crucial in preparing polymeric amphiphiles. The excellent biocompatibility and multivalency of both glycerol and triglycerol make them suitable monomers to construct macromolecular skeletons. Besides these, easy availability and remarkable aqueous solubility further enlarge their use in synthetic chemistry and give ample possibilities for creating fascinating entities for practical applications. The conversion of glycerol into azido-glycerol and azido-triglycerol further helped in differential functionalization of their polymers with various hydrophobic and hydrophilic groups in different ratios thereby assisting in tuning the amphiphilicity of resulting functionalized polymers. Herein, we review the enzymatic synthesis of glycerol, azido-glycerol and azido-triglycerol based amphiphilic polymeric architectures as nanocarriers for various bio-active species. Enzymatically synthesized linear copolymers synthesized by selective esterification of primary hydroxyl groups of glycerol and its derivatives with suitable diacids/diesters are explored in this review.

Indocyanine green (ICG) is a near-infrared dye for wide-ranging applications, but its utility for biological studies is limited due to poor aqueous stability and concentration-dependent aggregation. Aqueous polymeric micelles/micellar aggregates of amphiphilic copolymers could be used to protect indocyanine green (ICG) by encapsulation, which is used in laser-mediated photothermal therapy (PTT) and photodynamic therapy (PDT). The sugar–PEG-based amphiphilic copolymers were synthesized using Novozym 435-catalyzed transesterification reaction under bulk conditions for encapsulation of ICG. A dye loading study revealed that micelles derived from copolymers having decanoylated and myristoylated sugar moieties encapsulate 62% and 92% of the ICG, respectively, with a multi-fold increase in its aqueous stability. Furthermore, an efficient internalization of micelles of acylated amphiphilic copolymers in aqueous medium was demonstrated by incubating cells with Nile red-encapsulated amphiphiles.

A convergent template assisted synthesis of sugar-based chiral macrocycles has been achieved. The host-guest inclusion studies have revealed significant interactions of the synthesized macrocycle with primary over secondary ammonium salt. The chiral macrocyle also discriminates between D- and L-phenylalanine methyl ester hydrochlorides as revealed by (1)H NMR spectral studies on the mixture of the host and the guest molecules.

The novel unsymmetrical 3,5-dialkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines and 5-acetyl-3-alkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines (coumarinyl-1,4-dihydropyridines) have been synthesized by Knoevenagel condensation of 4-formyl-7,8-dimethoxycoumarin with alkyl acetoacetates in the presence of AlCl3 followed by cyclization of the resulted Knoevenagel product with other alkyl acetoacetate or acetyl acetone and ammonium acetate. The structure of the intermediate Knoevenagel product and the cyclized unsymmetrical coumarinyl-1,4-dihydropyridines has been established on the basis of their spectral data analysis and single-crystal X-ray diffraction analysis. The observed conformation of the coumarinyl-1,4-dihydropyridines holds the key to promising calcium antagonistic activity of the synthesized coumarinyl-1,4-dihydropyridines.

Three LNA-based mercaptoacetamido-linked nonionic nucleoside dimers TL-S-T, T-S-TL, and TL-S-TL have been synthesized by HOBT and HBTU catalyzed condensation of silyl-protected 2-S-(thymidin-5 '-yl)mercaptoacetic acid or 2-S-(2 '-O,4 '-C-methylenethymidin-5 '-yl)mercaptoacetic acid with 3 '-amino-3 '-deoxy-5 '-O-DMT-2 '-O,4 '-C-methylenethymidine or with 3 '-amino-3 '-deoxy-5 '-O-DMT-β-thymidine followed by desilylation of the protected dimers. The 3 '-O-phosphoramidite derivative of one of the nucleoside dimers was successfully prepared by condensation with [P(-Cl)(-OCH2CH2CN)-N(iPr)2}] in DCM in the presence of N,N-diisopropylethylamine (DIPEA), which is a building block for the preparation of mercaptoacetamido-linked oligonucleotides of therapeutic applications.

A convenient route has been developed for the diastereoselective synthesis of β-C-glycopyranosyl aldehydes from D-glucose, D-mannose, and D-galactose. The key step in the synthesis of C-glycosyl aldehydes is the aryl driven reductive dehydration on 1-phenyl-2-(2',3',4',6'-tetra-O-acetyl-β-D-glycopyranosyl)ethanone to afford alkenes, which on oxidation afford the desired compounds in good yield. β-C-Glycopyranosyl aldehydes have been converted to 2,6-anhydro-heptitols in quantitative yields. The 2,6-anhydro-heptitols derived from D-mannose and D-galactose are enantiomeric and are useful linkers for the synthesis of macrocycles/amphiphiles of complementary chirality.

Introduction: The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Methods: Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Results: Although multiple SET variables correlated with the RRRS on univariate analyses, only VE/VCO2 (r = 0.57, p &lt, 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the VE/VCO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). Conclusion: SETs, particularly the VE/VCO2, appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Introduction: Spontaneous bacterial peritonitis (SBP) requires rapid diagnosis for the initiation of antibiotics. Its diagnosis is usually based on manual examination of ascitic fluid (AF) having long reporting time. AF infection is diagnosed when the fluid polymorphonuclear leukocyte (PMNL) concentration ≥250 cells/mm 3 . Aims and Objectives: Aim was to evaluate the diagnostic utility of leukocyte esterase (LE) reagent strip for rapid diagnosis of SBP in patients who underwent abdominal paracentesis and to calculate the sensitivity, specificity, positive, and negative predictive values. Materials and Methods: The study was carried out on 103 patients with ascites. Cell count of AF as determined by colorimetric scale of Multistix 10 SG reagent strip was compared with counting chamber method (PMNL count ≥250 cells/mm 3 was considered positive). Results and Observations: Of the 103 patients SBP was diagnosed in 20 patients, 83 patients were negative for SBP by manual cell count. The sensitivity and specificity of the LE test for detecting neutrocytic SBP taking grade 2 as cut off were 95% and 96.4% respectively, with a positive predictive value of 86.4% and a negative predictive value of 98.8%. Diagnostic accuracy of LE test was 96.1%. Discussion: There was a good correlation between the reagent strip result and PMNL count. The LE strip test is based on the esterase activity of activated granulocytes which reacts with an ester-releasing hydroxyphenylpyrrole causing a colour change in the azo dye of reagent strip. It is a very sensitive and specific method for the prompt detection of elevated PMNL count, and represents a convenient, inexpensive, simple, and bedside method for diagnosis of SBP. A negative LE test result excludes SBP with a high degree of certainty.