Synthesis of aza-analogues of acyclic and cyclic nucleosides

Aim of project
The goal of the project is the synthesis of acyclic azanucleosides 1 and cyclic aza-nucleosides 2, derivatives of pyrrolidine, which could be used in the treatment of viral infections and cancer diseases. Wanting to obtain acyclic azanucleosides which would posses improved biological properties we are going to synthesize their phosphono analogues. The synthesis of cyclic nucleosides will involve derivatives 2 possessing at the position 4’ tertiary carbon atom connected with two hydroxymethyl substituents. In their synthesis we are going to use derivatives of 5,5-bis(hydroxymethyl)-1-pyrroline and 5-acyloxy(or 5-alkiloxy)- 2,2-bis(hydroxymethyl)pyrrolidine, whose synthesis from nitroalkanes is well advanced. Both azanucleosides acyclic and cyclic will be sent to prof. E. De Clercq for antiviral screening.

Expected results
The outcome of the project will be new types of acyclic and cyclic nucleosides of potential antiviral and anticancer activity. The improvement of synthetic methods of azanucleosides and structural analysis will be achieved. Based on the results attained, synthesis of new types of nucleosides will be invented.