Organic chemistry

The topic of the project is the development of synthetic methodology for libraries of modified aryl- a hetaryl-C-nucleosides (ribo- and 2'-deoxyribonucleosides). 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 chemically and enzymatically incorporated to DNA and used in studies of mechanism of polymerases and for extension of the genetic alphabet.

Leading references:

Štambaský, J.; Hocek, M.; Kočovský, P.:
C-Nucleosides: Synthetic Strategies and Biological Applications.
Chem. Rev. 2009, 109, 6729-6764.

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.