Vitālijs Rjabovs

Synthesis of novel 3-deoxy-3-C-triazolylmethyl-allose derivatives and evaluation of their biological activity

AbstractRecently, monosaccharide-triazole conjugates have proved to possess a large variety of useful biological activities. This paper describes synthesis of a new series of 3-deoxy-3-C-triazolylmethyl-allose derivatives. These new compounds are obtained from acetonide-protected 3-deoxy-3-azidomethyl allose and commercial alkynes via Cu(I) catalyzed 1,3-dipolar cycloaddition. The obtained molecular scaffolds differ from those described earlier by the presence of a methylene linker (-CH2-) between the C(3) of allose and the triazole moiety. It was demonstrated that acetonide-protected monosaccharide, 3-deoxy-3-C-(4-phenyl-1H-1,2,3-triazol-1-yl)methyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose, inhibited α-L-fucosidase for 26% at 0.1 mM concentration, but a deprotected analog, 3-deoxy-3-C-(4-(4-tert-butylphenyl)-1H-1,2,3-triazol-1-yl)methyl-β-d-allofuranose, showed 15% inhibition of β-glucosidase at 1 mM concentration.

On Moffatt dehydration of glucose-derived nitro alcohols

Moffatt dehydration of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose derived nitro alcohols with a mixture of Ac(2)O and DMSO was reinvestigated. It was discovered that, regardless of the absolute configuration at C(3) of the sugar moiety, the dehydration provided exclusively the (3Z)-nitromethylene derivative. Slight modification of the workup conditions (pH⩾8, temperature: 25-30°C) gave exclusively a novel product, (3S)-3-deoxy-3-methylthio-3-C-nitromethyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. The latter was obtained by a Michael addition of thiomethylate anion to the previously reported nitromethylene derivative during the aqueous basic workup at ambient or slightly elevated temperature. The putative mechanism leading to the thiomethylate anion includes Pummerer rearrangement of DMSO and basic hydrolysis of thus formed methylsulfanylmethyl acetate.

Synthesis of 1,2,3-triazole-linked glycohybrids in the gluco-, gulo-, and allopyranose series

Ketone derived from diacetone-α-D-glucose is a suitable starting material for the synthesis of 3-C-linked glycohybrids containing 1,2,3-triazole moiety as an intersugar linkage. The pyranose tautomers of 3-deoxy-3-(1,2,3-1H-triazol-1-yl)glucose, 3-C-[(1,2,3-1Htriazol-1-yl)methyl]allose and 3-C-[(1,2,3-1H-triazol-1-yl)methyl]gulose moieties are released upon the acidic hydrolysis of the corresponding O-isopropylidene-protected furanosyl-type synthetic intermediates. Some of the title compounds show a rare property of activating β-galactosidase from Escherichia coli.

Synthesis of monomeric methylene-linked 1,2,3-triazole glycoconjugates from allo- and glucofuranoses

Carbohydrate–triazole conjugates proved themselves as valuable enzyme activity-modifying agents. Recent exploration of nontrivial conjugates in which the bonding is formed not at the glycosidic or terminal carbons of the carbohydrates, but at C-3 position showed a potential of this type of structures as the ligands for various glycosidases and galectins. Here, we report synthesis of protected monomeric 3-C-(triazolylmethyl)-substituted gluco- and alloconjugates. Diastereomeric azides are synthesized from common intermediate, 3-deoxy-1,2:5,6-di-O-isopropylidene-3-oxo-α-D-allofuranose, and used in Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reactions with commercial alkynes. The yields of the cycloaddition reactions are good to excellent under different catalytic conditions.

{(3aR,5S,6R,6aR)-5-[(R)-1,2-Di­hydroxy­eth­yl]-2,2-di­methyl­tetra­hydro­furo[2,3-d][1,3]dioxol-6-yl}methyl methane­sulfonate

In the title compound, C11H20O8S, the furanose ring has a pseudorotation phase angle equal to 31.3° and assumes a 3 T 4 conformation, with deviations of 0.297 (4) and −0.152 (4) Å for the corresponding C atoms. The dioxolane ring adopts an envelope conformation. One of the O atoms is at the flap and deviates from the least-squares plane formed by the other four ring atoms by 0.405 (2) Å. The dihedral angle between the planar fragments of the rings is 63.53 (8)°. In the crystal, molecules are associated into sheets perpendiculer to the b axis by means of O—H⋯O hydrogen bonds. A few weak C—H⋯O interactions are also observed.

Novel Ciprofloxacin Derivatives for Polymer-Based Drug Delivery Systems

Novel derivatives of fluoroquinolone antibiotic ciprofloxacin were synthesized. The modifications of both the N- and C-termini were focused on introduction of functionalized linkers that can be used for covalent attachment to natural or synthetic polymers with appropriate functional groups.

Stereoselective Michael addition of O-nucleophiles to carbohydrate-based nitro-olefin

Abstract Michael addition reactions of O-nucleophiles to C(3) exocyclic nitromethylene derivative of diacetone glucose are reported. The reactions with primary alcohols proceed at ambient temperature in the presence of different bases with good yields and give products with excellent diastereoselectivity. The addition of the nucleophile occurs from the β-face of the carbohydrate as shown by single crystal X-ray analysis. The reactions with secondary alcohols give low yields of products while phenolic compounds do not react. Under certain conditions, isomerization of starting material is observed.

Crystal structure of 3-de-oxy-3-nitro-methyl-1,2;5,6-di-O-iso-propyl-idene-α-d-allo-furan-ose.

The title compound, a nitro carbohydrate, consists of a substituted 2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxolane skeleton. The furanose ring adopts a oT 4 conformation.