Synthesis and biological evaluation of novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides as potential antiviral agents

Novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides were synthesized in this study. The introduction of two methyl groups in the 2′‐ and 3′‐position was accomplished by a Horner‐Wadsworth‐Emmons reaction and isopropenyl magnesium bromide addition, respectively. The construction of the required 4′‐quaternary carbon was carried out using a [3, 3]‐sigmatropic rearrangement. Bis‐vinyls were successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. The antiviral activities of the synthesized compounds were evaluated against HIV‐1, HSV‐1, HSV‐2 and HCMV. Compound 30 displayed moderate anti‐HCMV activity (EC 50 = 30.1 μg/mL), without exhibiting any cytotoxicity at up to 100 μM.