Andrey V. Shernyukov

Discovery of a new class of antiviral compounds: camphor imine derivatives.

A new class of compounds featuring a camphor moiety has been discovered that exhibits potent inhibitory activity against influenza A(H1N1)pdm09 and A(H5N1) viruses. The synthesized compounds were characterized by spectroscopic analysis; in addition the structures of compound 2 and 14 were elucidated by the X-ray diffraction technique. Structure-activity relationship studies have been conducted to identify the 1,7,7-trimethylbicyclo[2.2.1]heptanes2-ylidene group as the key functional group responsible for the observed antiviral activity. The most potent antiviral compound is imine 2 with therapeutic index more than 500.

Methods of the synthesis of A-seco derivatives of pentacyclic triterpenoids

The review considers the main methods for the synthesis of derivatives of A-seco pentacyclic triterpenoids by means of the Baeyer-Villiger reaction, the Beckmann rearrangement, and other oxidation processes.

Synthesis and biological activity of novel deoxycholic acid derivatives.

We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth.

Preparation and nitration of allobetulin seco-derivatives

2-Nitro-derivatives of allobetulone were prepared by reaction of allobetulin with nitric acid. 2β-Aminoallobetulin was synthesized by reduction of 2-nitrobetulone with LiAlH4. The corresponding allobetulin seco-derivatives were obtained via oxidation by H2O2 in the presence of K2CO3 of 2-nitroallobetulone and cleavage of 2,2-dinitroallobetulone by K2CO3 in H2O:THF.

Reduction of 2,3-Seco-28-oxo-19β,28-epoxy-18α-olean-2,3-dicarboxylic acid and its cyclic anhydride

Reduced derivatives of 2,3-seco-28-oxo-19β,28-epoxy-18α-olean-2,3-dicarboxylic acid and its cyclic anhydride were prepared. Reduction of the starting 2,3-secodicarboxylic acid by NaBH4–I2 produced the 2,3-seco-2,3-dihydroxy derivative. Reaction of the starting anhydride with LiAlH4 gave the 2,3-seco2,3,19β,28-tetrahydroxy derivative. Cyclization using acidic reagents of the 2,3-seco-2,3-hydroxy- and 2,3seco-2,3,19β,28-tetrahydroxy derivatives gave the corresponding cyclic ethers containing an oxepane ring. The anhydride ring was reduced by NaBH4 to the corresponding ε-lactone, the structure of which was confirmed by an x-ray crystal structure.

Noncatalytic bromination of benzene: A combined computational and experimental study

The noncatalytic bromination of benzene is shown experimentally to require high 5–14 M concentrations of bromine to proceed at ambient temperatures to form predominantly bromobenzene, along with detectable (<2%) amounts of addition products such as tetra and hexabromocyclohexanes. The kinetic order in bromine at these high concentrations is 4.8 ± 0.06 at 298 K and 5.6 ± 0.11 at 273 K with a small measured inverse deuterium isotope effect using D6‐benzene of 0.97 ± 0.03 at 298 K. These results are rationalized using computed transition states models at the B3LYP+D3/6‐311++G(2d,2p) level with an essential continuum solvent field for benzene applied. The model with the lowest predicted activation free energies agrees with the high experimental kinetic order in bromine and involves formation of an ionic, concerted, and asynchronous transition state with a Br8 cluster resembling the structure of the known Br9−. This cluster plays three roles; as a Br+ donor, as a proton base, and as a stabilizing arm forming weak interactions with two adjacent benzene CH hydrogens, these aspects together combining to overcome the lack of reactivity of benzene induced by its aromaticity. The computed inverse kinetic isotope effect of 0.95 agrees with experiment, and arises because CBr bond formation is essentially complete, whereas CH cleavage has not yet commenced. The computed free energy barriers for the reaction with 4Br2 and 5Br2 for a standard state of 14.3 M in bromine are reasonable for an ambient temperature reaction, unlike previously reported theoretical models involving only one or two bromines.

Configurational Stability of 1,1′-Bi-2-naphthol in Superacid System HSO 3 F–SbF 5 –SO 2 ClF

Although 1,1′-bi-2-naphthol (BINOL) is known to racemize in aqueous mineral acids and much more readily in superacids, it retains its initial configuration in one of the strongest superacid system, HSO3F-SbF5-SO2ClF due to protective C8,C8′-diprotonation.

Synthesis of Diastereomeric Spirocyclic Nitroxyl Radicals of 3-Imidazoline Series with Two Mesogenic Groups

Alkylaromatic α-hydroxylamino ketones with a p-hydroxy(alkoxy)aryl substituent were used for the preparation of stable diastereomeric spirocyclic nitroxyl radicals of 3-imidazoline series, having two different or identical mesogenic groups in the molecule. The molecular structure of these compounds was determined by NMR study of their diamagnetic reduced derivatives.