Many nucleoside and nucleotide analogs have been approved as efficacious and selective clinical antiviral drugs. However, emerging infectious viruses and ongoing viral mutations are a challenging problem for the scientific community. To tackle viral infections and viral drug resistance, continuous drug discovery and development is essential. In this effort, the synthesis of a 4′-α-fluoromethyl carbocyclic adenosine analog, and dioxolane derived 7-deazapurine nucleosides have been reported and evaluated as antiviral agents. The invented synthetic route for the synthesis of the 4ʹ-fluoro-methyl carbocyclic ring is novel and was utilized for the construction of the carbocyclic adenosine nucleoside (15). 7-Deazapurine dioxolane nucleoside analogs have been synthesized and evaluated for antiviral activity, and one analog has demonstrated potent Anti-Epstein-Barr virus (EBV) activity. On-going in-vitro testing on the synthesized nucleosides may lead to potent antiviral preclinical candidates and will open a new path of full structural-activity relationship evaluation.