Head: Prof. Nina N. Makhova (e-mail: mnnioc.ac.ru, tel. +7(499)135-5326)
The laboratory had been established in 1962 by Prof. G.A. Shvekhgeimer and headed by Prof. L.I. Khmelnitskii in 1964-1995.
Developing synthetic methods and examining the structure, reactivity, stereochemistry, and chemical transformation of nitrogen heterocycles: diaziridines, azetidines, 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-diones (bicyclic bisureas), their thia- and heteroanalogs, imidazotriazines, 1,2,5-oxadiazoles (furazans) and their N-oxides (furoxans), triazoles, pyrazines, tetrazines, etc.
Designing new efficient few-step eco-safe syntheses of prospective molecules based on green chemistry principles such as performing multi-step processes as a one-pot option without the isolation of intermediates and with the use of ionic liquids as alternative solvents.
A search of new biologically active compounds, primarily neuro- and cardiotropic and nitrogen oxide donors, structures with cytotoxic antimicrobial and antimycotic activity, etc. sourced from the above nitrogen heterocycles.
Two novel classes of neurotropic compounds, viz. diaziridines and bicyclic bisureas (BBUs), that directly impact the CNS were discovered. A representative of BBUs, 2,4,6,8-tetramethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione (Mebicar), has been implemented in medicinal practice as an efficient daytime tranquilizer. New types of nitrogen oxide donors such as furazano(furaxano)pyridazine-N,N-dioxide and (1,2,3-triazol-1-yl)furazan derivatives were found.
Nitrogen/oxygen-containing heterocyclic systems with unique properties were synthesized with the help of new simple approaches to a wide scope of functional furazan, furoxan, diaziridine, and azetidine derivatives.
New types of atomic rearrangements, incl. cascade, in a series of uncondensed furoxan and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine derivatives, were discovered. These led to new alternative methods of the synthesis of derivatives of 4-amino-5-nitro-1,2,3-triazoles, 1.2.3-triazole-1-oxide and 1-nitroalkyl-substituted 1,2,3-triazoles, 1,2,4- triazoles and 1,2,4-thiadiazoles, and imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazines.
Preparative techniques based on diastereoselective cyclocondensation of 4,5-dihydroxyimidazolidin-2-ones with acidic chiral ureido acids or 1-alkylimidazalones and imidazooxazolone with (R)-1-(1-phenylethyl)urea were developed to afford enantiomerically pure bicyclic bisureas, some of which appeared to have neurotropic activity.
New routes of the diaziridine cycle expansion were revealed in the interaction of trans- and cis-diaziridines with a broad range of dipolarophiles. These underlined the elaboration of new synthetic alternatives for preparing derivatives of imidazolidin-4-ones, substituted pyrazolines, 1,5-diazabicyclo[3.3.0]octanes, and new heterocyclic systems annelated with triazoline, thiodiazolidine, pyrazolidine, and pyrazole heterocycles that incorporate reactive functional groupings and pharmacophore heterocycles as substituents.
Ionic liquids (ILs) were found to show promise as substrate-specific recoverable solvents, promoters and catalysts for a variety of classic organic interactions such as 1,3-dipolar cycloaddition, Bischler-Napieralski, Henry and Mannich reactions, Schmidt and Chapman rearrangements, nucleophilic aromatic cine-substitutions, cycloreversion, etc. The research resulted in novel efficient and eco-safe methods comprised of few steps – intermediates are generated in situ, which allow syntheses of both known and new nitrogen heterocyclic structures and a number of aromatic and high energy molecules.
Four new methods for preparing glycoluril thioanalogs, new pharmacologically active substances with a wide scope of action – anxiolytic, cytotoxic and antibacterial, were developed. The methods base on two approaches: 1) triazine cycle narrowing in imidazo[4,5-e]-1,2,4-triazines under the impact of aromatic aldehydes or sodium nitrate in acidic media, and 2) cyclocondensation of 4,5-dihydroxyimidazolidin-3-ones (thiones) with monosubstituted ureas or potassium thiocyanate in acidic media.
An efficient methodology of the synthesis of energy-intensive polynitro secondary amines, s-tetrazine and azolo[b]-s-tetrazine derivatives, was developed. The target products are sourced from the single and readily available compound – 3,6-bis(3,5-dimethylpyrazol-1-yl)-s-tetrazine. In the first step, an annelated tetrazine, viz. [1,2,4]triazolo[4,3-b]-s-tetrazine, is generated and then the dimethylpyrazole cycle is substituted by energy-intensive hetarylamines. This is the first example of the application of combinatory chemistry in the area of energetic materials. More than one hundred compounds of this kind have been synthesized.