10.1021/jo962204x
This research study on the synthesis and conformational analysis of cyclohexane nucleosides, specifically focusing on 3-hydroxy-4-(hydroxymethyl)-1-cyclohexanyl purines and pyrimidines. The purpose of the study was to understand the correlation between the antiviral activity of these compounds and their conformational structure. The researchers synthesized the nucleosides using various nucleobases and ethyl 1,3-cyclohexadiene-1-carboxylate through a conjugated addition reaction and hydroboration of the cyclohexenyl precursor. Key chemicals used in the synthesis process included adenine, 2-amino-6-chloropurine, thymine, uracil, cytosine, and various protecting groups like monomethoxytrityl and trityl groups, as well as reagents such as DBU, TFA, and BH3-THF complex. The lack of antiviral activity observed in the synthesized compounds was linked to their conformation, which was deduced from NMR and X-ray analysis. The study concluded that the replacement of the ring oxygen with a methylene group in carbocyclic nucleosides led to a change in the preferred conformation of the nucleoside base from axial to equatorial, which might explain the loss of antiviral activity compared to anhydrohexitol nucleosides.