The research activity of the Department of Organic Chemistry developed from the combination of the traditional and modern trends of organic chemistry. Our projects related to synthetic fields and structure analyses are the following:
Isolation, structure elucidation, and synthesis of O-heterocycles and related compounds.
Isolation, structure elucidation and synthesis of naturally occurring complex heterocycles (flavonoids, isoflavonoids and related compounds) with potential biological activity is one of our main research fields. The chemistry of polihydroxylated and prenylated flavonoids and isoflavonoids, including chromeno-flavonoids isolated from plant sources is studied. This project has gained remarkable pharmacological interest due to the antihepatitic activity of silybin and its analogues. During these syntheses, thallium and hypervalent iodine chemistry are widely applied to develop new synthetic methods in the field of O -heterocyclic chemistry. In order to obtain enantiopure or enriched stereoisomers, enzymatic kinetic resolutions and chiral HPLC separation techniques are also used.
Comprehensive research is carried out for the exploration of novel synthetic methods of O - and S -heterocycles and their related compounds (benzopyrans, benzofurans, aurones, chromanones, flavonones, chromones) and anellation of novel heterocyclic rings. Enantioselective transformations of these compounds and their transformations to seven-membered cyclic derivatives (1,5-benztiazepins and –benzoxizepins) are studied. The reactions of benzylidenecyclanones with binucleophiles are also investigated. Enantiopure 2,3-dihydrobenzo[b]furan, 4 H -benzopyran and pterocarpan derivatives were synthesized and their chiroptical study allowed to establish general rules for the configurational assignment of natural products containing these chromophores.
Transformation of natural N-heterocycles and their potentially pharmacologically active derivatives
In the transformation of morphine and its related compounds, our interest is mainly focused on the N -demethylation and N -alkylation of morphine derivatives. The applicability of the these substrates are studied in Mitsunobu-reaction and Diels-Alder transformations. The study of compounds with aporphine skeleton, obtained by the rearrangement of morphinans (e.g. thebaine), is also of importance. The preparation of derivatives substituted in rings A and B and new chemoselective O -demethylation procedures are investigated. As for the pharmacological properties of these compounds, their effects on opiate and dopamine receptors were mainly studied.
Research on carbohydrates and their derivatives
Synthesis and structure elucidation of C -glycosyl derivatives; investigations into and applications for preparative purposes of radical mediated transformations of carbohydrate derivatives; development of new synthetic methodologies for the preparation of glycals and their C- 1-substituted derivatives, as well as exo-glycals; preparation of precursors for glycosylidene- and glycosylmethylene carbenes, as well as glycosyl nitrenes and investigation of their reactivity; synthesis of glycosidase and glycogen phosphorylase inhibitors, among them glucopyranosylidene-spiro-heterocycles and N -acyl- N '- b - D -glucopyranosyl ureas, study of their structure-activity relationships; synthesis of glycomimetics and glycopeptidomimetics, especially anomeric a -amino acid derivatives.
Diastereoselective synthesis of glycosyl azides; transformation of simple carbohydrates to 2-polyhydroxyalkyl-thiazolidine-4-carboxylic acids, 4,5-dihydro-1,3,4-thiadiazoles, and N 1 -substituted 1,2,4-triazole nucleosides.
Stucture analysis of biologically active molecules by spectroscopic methods
The structure and intermolecular interaction of biomolecules (carbohydrates, aminoglycosides and macrolide antibiotics, peptides, glycopeptides, flavanoids and morphine alkaloids) are thoroughly studied by modern two-dimensional NMR techniques in solution. Research is pursued for the mass spectrometric (EI and CI fragmentation, ion stability, rearrangements), vibrational (IR) and chiroptical (UV, CD) characterization of flavonoids, carbohydrates, alkaloids and antibiotics. Modern separation techniques (GC, HPLC) are applied in the chemistry of natural products, especially for the separation of stereoisomers of chiral compounds. The relationship between the molecular recognition and separation is studied in detail. Online HPLC-CD measurements are successfully applied to determine the absolute configurations of flavonoids in their mixture containing multiple stereogenic centres. The instrumental background of the Department (CH analyzer, NMR-spectrometers, GC-MS , MS -MS and HPLC-MS, chiral HPLC coloumns, polarimeter, GC, FT-IR and UV/VIS spectrofotometer, CD spectropolarimeter, HPLC-CD) is ensured.