Head: Dr. Tibor Kurtán
Teaching staff involved in the programme:
- Ilona Bakai-Bereczki
- Teréz Barna
- Gyula Batta
- Éva Bokor
- Anikó Borbás
- Magdolna Csávás
- Anikó Fekete
- Erzsébet Fekete
- Gyöngyi Gyémánt
- Mihály Herczeg
- Pál Herczegh
- László Juhász
- Éva Juhászné Tóth
- Levente Karaffa
- János Kerékgyártó
- Attila Kiss
- Krisztina Kónya
- Tibor Kurtán
- Attila Mándi
- László Somsák
- László Szilágyi
- István Timári
- Marietta Vágvölgyiné Tóth
Research topics:
Synthesis, selective transformations and structural analysis of condensed chiral O- and O,N-heterocycles with potential pharmacological activity. Application of domino cyclization reactions to prepare condensed and spirocyclic bioactive heterocycles having novel skeleton and containing condensed benzene and/or heteroaromatic subunits. Stereoselective synthesis and pharmacological investigation of benzene-fused homo- and heterodimeric heterocycles containing central and axial chirality elements. Application of chiroptical and in silico methods to study the absolute configuration and conformation of natural and synthetic derivatives.
Synthesis of carbohydrate-containing, carbohydrate-based natural compounds, their analogues and building blocks. Design and synthesis of glycomimetics and enzyme inhibitors. Study of the mechanisms of action of glycoenzymes. Study of carbohydrate-protein interactions using modern instrumental methods.
Description of the Doctoral Programme
More than half of the known organic compounds are considered heterocycles, and in the vast majority of them, the heteroatom is nitrogen, sulphur and oxygen. Heterocyclic derivatives provide the skeleton of numerous natural pharmacologically important groups of compounds such as flavonoids, alkaloids, antibiotics, and play a fundamental role in biochemical processes of living organisms. The majority of naturally occurring and synthetic pharmaceuticals and agrochemicals contain at least one heterocycle, the efficient and stereoselective preparation of which is a major challenge for organic synthetic chemistry.
The most abundant and widespread carbohydrates on earth usually exists in (hetero)cyclic form. The study of carbohydrates is a more or less separate field of organic and biochemistry, due to the large number of functional groups and stereogenic centers, as well as their biological properties. However, due to the mutual influence with other scientific fields (e.g. analytics, biomedicine, materials science), we can now speak of an independent carbohydrate science.
Glycobiology, the study of the biological role, biosynthesis and transformation of carbohydrates, has demonstrated the key role of sugar derivatives and their conjugates, e.g. glycoproteins and glycolipids, in several fundamental recognition processes. The rapid development of this field and of carbohydrate science continues today, progressing synergistically with improvements in separation techniques and structural elucidation methods. Like other "omics" fields (e.g. genomics, proteomics), the systematic study of the carbohydrate content of a cell or organism (glycan, glycome) is now part of the subject of glycomics.
The biological roles of heterocycles and carbohydrate derivatives are mediated by their interactions with macromolecules, most often with proteins (receptors/lectins, (glyco)enzymes, antibodies) that recognise, transform or induce immune responses to (small) molecules. These interactions can also be studied using chemical biology methods. This involves 'perturbing' biological systems in vitro or in vivo with small molecules and inferring the essential properties of the system from the response to these perturbations. This information can be used, among other things, in drug design.
The above gives rise to important areas of research for both synthetic carbohydrate chemistry and heterocyclic chemistry: the preparation of natural compounds (e.g. oligosaccharides, glycoproteins, glycolipids, alkaloids, antibiotics) and/or their essential constituents (e.g. N- and O-glycosylated amino acids, peptides, heterocyclic scaffolds); the synthesis of mimetics (compounds structurally and/or functionally analogous to naturally occurring substances: e.g. C-glycosyl derivatives, neoglycoconjugates, glycodendrimers, vaccines, bioisostere compounds); the design and synthesis of inhibitors that may provide the possibility to interfere with biochemical processes.
Our doctoral program offers training and research opportunities in these areas:
Development of carbohydrate protective groups and their application to the synthesis of biologically active oligosaccharides; use of cyclodextrins for the preparation of linear glycoside derivatives; synthesis of N-glycans and N-glycopeptides; transformations of the anomeric centre of carbohydrates by radical, anionic, carbenic reactions; design and preparation of glycomimetics (e.g. carbohydrate sulphonic acids, derivatives containing non-classical glycosidic bonds, C-glycosyl compounds, neoglycoproteins, carbohydrate-amino acid hybrids).e. g. carbohydrate sulphonic acids, derivatives with non-classical glycosidic bonds, C-glycosyl compounds, neoglycoproteins, carbohydrate-amino acid hybrids); design and preparation of glycoenzyme inhibitors (e.g. glycoside hydrolase, neuraminidase, glycosyltransferase, glycogen phosphorylase); design and synthesis of SGLT inhibitors; investigation of transformation possibilities of unsaturated carbohydrate derivatives; preparation of platinum metal complexes containing a carbohydrate moiety; Glycoenzyme binding site mapping, active site and mechanism of action studies; enzyme catalysed syntheses; lectin inhibitor design and synthesis; carbohydrate-protein interaction studies using mass spectrometry, ITC and NMR methods.
Stereoselective synthesis of chiral heterocycles condensed with benzene or heteroaromatic units by domino ring closure reactions and their further transformations; elucidation of the stereochemistry of chiral targets and exploration of the stereoselectivity of the reactions by combined structural (chiroptical spectroscopy, X-ray diffraction, 2D NMR) and in silico (DFT mechanism calculations, OR, ECD, VCD calculations) methods; investigation of the efficient production of polycyclic, condensed or bridged heterocycles by domino reactions; specific ring-closure reactions (e.g. oxa-Pictet-Spengler, intramolecular oxa-Michael, hetero Diels-Alder) for the formation of heterocyclic systems. Stereoselective preparation of biaryl-type homo- and heterodimeric heterocycles containing central and axial chirality elements for pharmacological and stereochemical studies. Investigation of antiproliferative, neuroprotective and antimicrobial activity on chiral heterocyclic target compounds.
OR, ECD (HPLC-ECD) and VCD characterisation of natural and synthetic heterocycles and DFT calculation of the chiroptical data. DFT calculation of NMR chemical shift values and coupling constants for the determination of relative configuration. DFT calculation of ring-closure reaction mechanisms and determination of activation parameters.
Study of metal-free and metal-catalysed cross-coupling reactions (C-C and C-N bond formation), elucidation of their selectivity (e.g. Suzuki-Miyaura, Heck-Mizoroki, Sonogashira, Buchwald-Hartwig and Ullman couplings); study of cross-coupling reactions of O-heterocyclic compounds based on C-H activation; synthesis of heterocyclic compounds with biological activity. Closely linked to the above is the provision and development of the necessary analytical background (GC, HPLC, SCF-LC, GC-MS, HPLC-MS).
The actual research topics from these areas change annually and are generally characterised by the fact that they include chemical, biochemical, structural and chemical-biological aspects of the areas under investigation.