Maxim A. Bastrakov

3-R-4-Nitro-6,7-furoxanobenzo[ d ]isoxazoles – a new type of condensed nitroarenes capable of Diels–Alder reaction

Pericyclic [4+2] cycloaddition (Diels–Alder reaction) of nitrofuroxanobenzo[d]isoxazoles, capable of acting both as dienophiles (at the C=CNO2 bond) or heterodienes (at the C=C–N(O)=O fragment) was used to synthesize a new type of condensed polycyclic systems. The obtained compounds combining in one molecule two pharmacophore moieties, furoxan (nitric oxide donor) and substituted isoxazole, may be considered as a potential basis for the design of compounds with dual biological activity.

8-R-5,7-Dinitroquinolines in [3+2] cycloaddition reactions with N-methylazomethine ylide

Novel derivatives of isoindole and dihydroisoindole fused to the pyridine ring were obtained by 1,3-dipolar cycloaddition reactions of N-methylazomethine ylide with substituted 5,7-dinitroquinolines. The substituents in the benzene ring were found to affect the cycloaddition outcome.

Synthesis of novel polycyclic heterosystems from 5-nitro[1,2,5]selenadiazolo[3,4-e]benzofuroxans

A method for the preparation of 5-nitro[1,2,5]selenadiazolo[3,4-e]benzofuroxan has been developed. Employing the reactivity of this compound in pericyclic (4+2) and (3+2) cycloaddition reactions as a dienophile or dipolarophile (at the C=C–NO2 bond) with a heterodiene (fragment C=C–N(O)=O) representatives of novel types of fused polycyclic heterosystems were synthesized.

Quantum-chemical and NMR study of nitrofuroxanoquinoline cycloaddition

Using DFT/B3LYP and ab initio RHF quantum-chemical calculations in the triple-zeta basis set 6-31++G** the endo and exo cycloaddition mechanism for the interaction of ethyl vinyl ether, trimethylsilyloxybutadiene, or cyclopentadiene with 5-nitro-7,8-furoxanoquinolines was studied in details. Considering that both in solutions and crystals nitrofuroxanoquinoline exists as an inseparable mixture of two N-oxide tautomers, all cycloaddition processes were studied for both of them. The studied mechanisms practically do not depend on the location of the exocyclic oxygen atom in nitrofuroxanoquinoline molecule. At the first step of all reactions the conjugated nitroarene fragments C=C–N=O react with nucleophilic reagents following the mechanism of endo-[4+2] cycloaddition with inverse electronic demand. Further (in the cases of trimethylsilyloxybutadiene and cyclopentadiene) endo-[4+2] cycloadducts recyclize spontaneously according to the mechanism of [3,3] sigmatropic rearrangement into more thermodynamically stable, experimentally detected endo-[2+4] cycloadducts. Both endo-[4+2] and endo-[2+4] cycloadducts obtained from cyclopentadiene and nitrofuroxanoquinoline have been experimentally isolated and characterized. For this case, the kinetic and activation parameters of [4+2] → [2+4] transformation have been studied by 1H NMR method, which have shown an excellent agreement with quantum-chemical results. In all cases the exo processes are one-step reactions, less favorable kinetically than their endo competitors.

Synthesis of 3-R-2-aryl-4,6-dinitroindoles and specific features of their reactions with anionic nucleophiles

Reaction of different anionic S-nucleophiles with 3-R-2-aryl-4,6-dinitroindoles led to a regiospecific nucleophilic substitution of the nitro group in position 4 with 6-NO2 group remaining intact. The representatives of some peri-annulated polycyclic systems were synthesized on the basis of the substitution products.

CYCLOADDITION REACTIONS IN THE SYNTHESIS OF ISOINDOLINES (MICROREVIEW)

A summary of the most recent approaches toward isoindoline derivatives via cycloaddition reaction is discussed. The microreview covers the latest selected examples (2010–2017) on the synthesis of isoindolines that are divided into several distinct categories depending on the structure of the starting compound – intramolecular [3+2] cycloaddition of azides, [3+2] cycloaddition of azomethine ylides, [2+2+2] cycloadditions, and others.

Nitrobenzofuroxane derivatives as dual action HIV-1 inhibitors

Human immunodeficiency virus type 1 (HIV-1) causes one of the most dangerous diseases, HIV infection and AIDS. The search for new inhibitors of the virus still remains an urgent task. One of approaches to suppress the HIV infection is the use of dual action HIV-1 inhibitors, i.e. inhibitors targeting two stages of the viral life cycle. The catalytic domain of HIV-1 integrase shares similar structural organization with the ribonuclease (RNase H) domain of HIV-1 reverse transcriptase, and therefore an approach aimed at creation of dual action inhibitors which would simultaneously inhibit HIV-1 integrase and RNase H seems to be very promising. In this work we have synthesized a series of 6-nitrobenzofuroxane derivatives and studied their inhibitory activity towards two HIV-1 enzymes, integrase and RNase H.

4-R-7-Nitrobenzofurazans in [3+2] cycloaddition reactions with N -methylazomethine ylide

A number of new tetrahydroisoindole derivatives fused with the furazan ring were synthesized based on the 1,3-dipolar cycloaddition of N-methylazomethine ylide with substituted 4-nitrobenzofurazans. Substituents in the benzene ring were found to affect the cycloaddition process.

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

4-Aza-6-nitrobenzofuroxan (ANBF) reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts – 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic β-diketones, which exist mainly in the enol form in polar solvents, the reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems.

Synthesis of pyrazole- and thiazole-annulated 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes

The previously unknown 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes fused to the pyrazole or thiazole rings were synthesized by the reductive cyclization of m-dinitroindazoles and benzothiazoles. The method is based on the reduction of carbon-carbon bonds in the benzene ring, which are activated by the meta-nitro groups, with NaBH4 followed by the Mannich reaction with formaldehyde and primary amines.