This thesis is framed within a project that pursues the synthesis of novel nucleoside analogues and their evaluation as potential antiviral agents. Specifically, the main part of this work is devoted to the preparation of cyclobutane nucleoside analogues, using the [2+2] photocycloaddition reaction of chiral 2(5H)-‐furanones to 1,1-‐diethoxyethylene as a key step to construct the cyclobutane ring. Using this methodology, a new family of conformationally restricted nucleosides by the presence of a functionalized cyclobutane ring has been synthesized. The biological activity of these novel nucleosides against several viruses has been evaluated, although none of them showed significant activity. The lack of anti-‐HIV activity of the newly synthesized compounds, despite their structural similarity with efficient drugs (e.g. d4T), prompted us to carry out a docking study to shed light on the activation process of these nucleosides as well as their binding with the enzyme reverse transcriptase from HIV. In addition, a new synthetic approach towards cyclobutane L-‐nucleoside analogues has been developed, allowing the preparation of a new set of this class of compounds. These nucleosides have been screened for antiviral activity and although one compound exhibited weak activity against influeza viruses, it also showed significant cytotoxicity. The last part of the thesis is focused on the synthesis of double-‐headed nucleosides, synthetic nucleosides featuring an additional nucleobase. This work has been carried out during a three-‐month stay at the Nucleic Acid Center in the University of Southern Denmark (Odense).
Stereoselective Synthesis of Cyclobutane Nucleoside Analogues
Figueras Sorinas, A. (Author). 18 Dec 2012
Student thesis: Doctoral thesis
Student thesis: Doctoral thesis