Pál Herczegh

Anti-influenza virus activity and structure-activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

Abstract Previous studies have demonstrated that glycopeptide compounds carrying hydrophobic substituents can have favorable pharmacological (i.e. antibacterial and antiviral) properties. We here report on the in vitro anti-influenza virus activity of aglycoristocetin derivatives containing hydrophobic side chain-substituted cyclobutenedione. The lead compound 8e displayed an antivirally effective concentration of 0.4μM, which was consistent amongst influenza A/H1N1, A/H3N2 and B viruses, and a selectivity index ≥50. Structural analogues derived from aglycovancomycin were found to be inactive. The hydrophobic side chain was shown to be an important determinant of activity. The narrow structure–activity relationship and broad activity against several human influenza viruses suggest a highly conserved interaction site, which is presumably related to the influenza virus entry process. Compound 8e proved to be inactive against several unrelated RNA and DNA viruses, except for varicella-zoster virus, against which a favorable activity was noted.

Elaboration of a novel type of interglycosidic linkage: syntheses of disulfide disaccharides

Abstract Asymmetric non-reducing disaccharides containing an interglycosidic disulfide linkage were synthesised under mild conditions through reaction of tetraacetyl-β- d -glucopyranosyl methanethiolsulfonate with O -acetylated 1-thio-aldopyranoses. The preferred conformation around the SS bond is close to that observed in unconstrained disulfides (−90°).

Synthesis of S-Linked Glycoconjugates and S-Disaccharides by Thiol–Ene Coupling Reaction of Enoses

Free-radical hydrothiolation of the endocyclic double bond of enoses is reported. Reaction between 2-acetoxy-D-glucal and a range of thiols including amino acid, peptide, glycosyl thiols, and sugars with primary or secondary thiol functions gave S-linked α-glucoconjugates and S-disaccharides with full regio- and stereoselectivity. Addition of glycosyl thiols to a 2,3-unsaturated glycoside also proceeded with good selectivity and afforded a series of 3-deoxy-S-disaccharides.

Synthesis of osteotropic hydroxybisphosphonate derivatives of fluoroquinolone antibacterials

1-Hydroxybisphosphonate derivatives of ciprofloxacin, gatifloxacin and moxifloxacin have been synthesized using Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. The 1,2,3-triazol linked hydroxybisphosphonate derivative of ciprofloxacin exhibited antibacterial activity comparable to the parent antibiotic and all fluoroquinolone-bisphosphonates displayed osteotropic properties in a bone model.

Cycloaddition reactions of carbohydrate derivatives. Part IV. Synthesis of a tetrahydroxyindolizidine through a cyclic nitrone prepared from D-xylose.

Intramolecular conjugate addition of the oxime from aldehyde 5 led to the formation of cyclic nitrone 6. 1,3-Dipolar cycloaddition of the latter with methyl acrylate gave the bicyclic 7 with high diastereoselection. Subsequent four-step transformation of 7 resulted in the tetrahydroxyindolizidine derivative 11.

Cycloaddition Reactions of Carbohydrate Derivatives. Part III. A New Route to Swainsonine Analogs.

Abstract Swainsonine analogs 10 and 12 have been synthesized from D- and L-arabinose, respectively, using cyclocondensation of azomethines with Danishefskys diene followed by stereoselective carbonyl and double bond reduction of the resulting pyridones, chain shortening and ring closure by reductive amination.

Thiazole C-nucleosides. III, Synthesis of pyranose analogues of tiazofurin

Abstract A large-scale synthesis of 3,4,5-tri-0-acetyl-2,6-anhydro-L-mannono-and-D-gulonothioamides (5, 6) has been achieved from the corresponding nitriles. The Hantzsch reaction of (5) or (6) with ethyl bromopyruvate afforded the expected thiazoles (7.8) only in a low yield along with furan derivatives (9-11), the formation of which is rationalized by an acid-catalysed rearrangement-elimination process. The some Hantzsch reaction in the presence of barium carbonate yielded hydroxythiazolines (16,17). Attempted dehydration of (16) or (17) with trifluoroacetic anhydride or trifluoroacetic anhydride/pyridine resulted in the formation of pent-1′-enopyranosylthiazoles (18-20). Deprotected thioamides (24,25) furnished with ethyl bromopyruvate thiazoles (27,28). The obtained thiazole esters (7,8, 18-20. 27,28) were transformed into new tiazofurin analogues (12, 13, 21- 23).

Diazo Transfer−Click Reaction Route to New, Lipophilic Teicoplanin and Ristocetin Aglycon Derivatives with High Antibacterial and Anti-influenza Virus Activity: An Aggregation and Receptor Binding Study

Semisynthetic, lipophilic ristocetin and teicoplanin derivatives were prepared starting from ristocetin aglycon and teicoplanin psi-aglycon (N-acetyl-D-glucosaminyl aglycoteicoplanin). The terminal amino functions of the aglycons were converted into azido form by triflic azide. Copper catalyzed 1,3-dipolar cycloaddition reaction with lipophilic alkynes resulted in the title compounds. Two of the teicoplanin derivatives showed very good MIC and MBC values against various Gram-positive bacteria, including vanA enterococci. The aggregation and interaction of a n-decyl derivative with bacterial cell wall components was studied. One of the lipophilic ristocetin derivatives displayed favorable anti-influenza virus activity.

Sulfonic acid analogues of the sialyl Lewis X tetrasaccharide

Abstract Sulfonomethyl mimics of 2-ulosonic acids were prepared by addition of the ethyl methanesulfonate carbanion on aldonolactone derivatives, and these were converted into new analogues of the sialyl Lewis X tetrasaccharide.

SULFONOMETHYL ANALOGUES OF ALDOS-2-ULOSONIC ACIDS. SYNTHESIS OF A NEW SIALYL LEWIS X ANALOGUE

Abstract Sulfonomethyl derivatives of aldos-2-ulosonic acids have been synthesized by addition of the ethyl methanesulfonate carbanion to aldonolactones. A sulfonylated mimic molecule of the sialyl Lewis X tetrasaccharide has been prepared by using a new sulfonomethyl ulosonic acid analogue.