Institute of Bioorganic Chemistry and Petrochemistry National Academy of Science of Ukraine

Department 1


The Fine Organic Synthesis Department of the Bioorganic Chemistry and Petrochemistry Institute of the National Academy of Sciences of Ukraine was organized in 1984.

The head of the Department is Igor Ivanovich Gerus, Ph.D.

Academician NAS Ukraine, Prof. V. P. Kukhar was a Head of the Department for a long time.

The main trend of scientific investigations of the Department is to develop methods for directed synthesis of biologically active natural compounds and their synthetic analogs. Among a number of natural compounds the polyenoic acids, amino acids and synthons for their synthesis attract our attention most of all.

The substitution of different blocks in natural compounds for organoelement ones is known to lead to impressive results in modulation of biological activity. This is the reason we study the problems of synthesis of fluorine- and phosphorus-containing polyenes and amino acids. We have developed the methods of difluoroacetylene fragment construction and introduction of this structural block into the eicosanoid structure at the desired position of difluoromethylene group. The method gives a possibility to introduce difluoromethylvinyl and difluoroacetylene groups into the structures of various unsaturated natural compounds.

We have developed new approaches to synthesis of fluorine-containing amino acids. We synthesize aliphatic and aromatic fluorine-containing amino acids as both racemic mixtures and individual enantiomers. To realize these tasks we are developing the methods to construct the fluorine-containing blocks needed as well as to introduce them into desired structures, the methods of asymmetric synthesis using asymmetric induction or direct fragment introduction in enantiopure molecules. The resolution of enantiomers can be successfully realized with enzyme application. By these approaches we have prepared a number of derivatives of fluorine-containing phenylalanines and alanines, [alpha]-trifluoromethylsubstituted amino acids, perfluoroalkyl- and polyfluoroarylserines, [beta]-amino acids, etc.

The similar approaches are used to synthesize phosphorus-containing analogs of natural amino acids. We are developing the methods of asymmetric synthesis of phosphorus-containing amino acids with application of chiral reagents. The kinetic investigation of the reactions of phenacyl derivatives of aminophosphonic acids gave a possibility to develop convenient methods of enantiomer resolution with using penicillin amidase, as well as to realize the peptide synthesis with the introduction of any desired enantiomer.

Methods for introducing phosphorus-containing groups into lipid structures and synthesis of natural phosphates are being developed with application of available silyl derivatives of phosphorus acid. The analogs of glycerol phosphates, PAF and other substances of similar nature were obtained.

Based on amino acids prepared some bioactive peptides being under investigation in laboratories of the Institute and other institutions were obtained with the desired substitution of fragments in peptide molecules. The peptides of predicted antiviral actions, inhibitors of some enzymes,. antimicrobial preparations, etc. have been obtained. Fluorine-containing eicozanoids were used as substrates and inhibitors of lipoxygenase pool.
Cage compounds adamantane and cubane, their structural analogs are studied as structural matrices in synthesis of various derivatives of these potentially bioactive compounds. We have created the original methods of functional groups introduction into adamantane and bishomocubane structures in liquid bromine medium, developed fluorination methods and methods of fluorine-containing group introduction, syntheses of hydroxy and amino derivatives of these substances, etc.

Today the main attention is paid to development of asymmetric synthesis methods, application of asymmetric induction and enzymes as synthetic tools, construction of single stereochemically individual synthons of a wide potential for directed synthesis of substances desired.

These investigations are based on exploration of modern methods in structural determination of compounds and chromatography. We develop actual problems in theory and practice of HPLC, create convenient resolution methods of enantiomers of fluorine-containing eicosanoids, fluorine- and phosphorus-containing amino acids, peptides, etc. The synthesis of new compounds is based on determinations of their structure by NMR, IR, UY, OR spectroscopy.

Collaboration of scientists of the Department with other scientific groups and laboratories at the Institute and outside gives a possibility to find actual problems to solve and to attain the decisions needed. So we are ready for new collaboration and joint investigations.