Introducing structural diversity into the nucleoside scaffold for use as potential chemotherapeutics has long been considered an important approach to drug design. In that regard, we have designed and synthesized a number of innovative 2′-deoxy expanded nucleosides where a heteroaromatic thiophene spacer ring has been inserted in between the imidazole and pyrimidine ring systems of the natural purine scaffold. The synthetic efforts towards realizing the expanded 2′-deoxy-guanosine and -adenosine tricyclic analogues as well as the preliminary biological results are presented herein.