Synthesis and Biological Evaluation of Methylenecyclopropane Analogues of Nucleosides

Germain Obame (1) , Paul Brémond (1) , Christophe Pannecouque (2) , Gérard Audran (1)

1 ICR - Institut de Chimie Radicalaire
2 Department of Microbiology and Immunology, Rega Institute for Medical Research

Starting from a chiral methylenecyclopropane building block, readily obtained by enzymatic desymmetrization of a meso-diol, two types of methylenecyclopropane analogues of nucleosides were synthesized. The first type of nucleosides was obtained from the direct coupling of the chiral building block with 6-chloropurine under Mitsunobu reaction conditions followed by the functionalization of the purine base. The second type of nucleosides featured a Curtius rearrangement as the key step and the uracil heterocycle was then constructed by a linear methodology. These derivatives were evaluated as potential agents against important viral pathogens. None of the new compounds had significant antiviral activity at a concentration of 100 g/mL, which was the highest concentration tested.

Domains: Chemical Sciences

Germain Obame, Paul Brémond, Christophe Pannecouque, Gérard Audran. Synthesis and Biological Evaluation of Methylenecyclopropane Analogues of Nucleosides. Synthesis: Journal of Synthetic Organic Chemistry, 2013, 45 (18), pp.2612--2618. ⟨10.1055/s-0033-1339311⟩. ⟨hal-01460478⟩