HomePh.D. Study at IOCBArchive - 2011Organic chemistry

Organic chemistry

Tutor Doc. Ing. Michal Hocek, DSc.
Team Michal Hocek
Topic Syntheses of novel types of C-nucleosides for biological activity screening and studying of mechanism of polymerases

The topic of the project is the development of synthetic methodology for libraries of modified aryl- a hetaryl-C-nucleosides (ribo- and 2'-deoxyribonucleosides, as well as nucleosides with modified sugar-part). Diverse C-glycosidation reactions will be studied for preparation of mono- a dihalo (het)aryl C-nucleosides. These intermediates will be further used in various Pd-catalyzed cross-coupling reactions, nucleophilic substitutions and carbonylations for the synthesis of the target C-nucleosides. The resulting nucleosides will be submitted for cytostatic and antiviral activity screening and chemically and enzymatically incorporated to DNA and used in studies of mechanism of polymerases.

Leading references:
1. Štambaský, J.; Hocek, M.; Kočovský, P. "C-Nucleosides: Synthetic Strategies and Biological Applications" Chem. Rev. 2009, 109, 6729-6764.
2. Joubert, N.; Pohl, R.; Klepetářová, B.; Hocek, M. "Modular and Practical Synthesis of 6-Substituted Pyridin-3-yl C-Nucleosides" J. Org. Chem. 2007, 72, 6797-6805.
3. Štefko, M.; Slavětínská, L.; Klepetářová, B.; Hocek, M. "A General and Efficient Synthesis of Pyridin-2-yl C-Ribonucleosides Bearing Diverse Alkyl, Aryl, Amino and Carbamoyl Groups in Position 6" J. Org. Chem. 2010, 75, 442-449.