Nucleosides and their analogues are of immense importance and they are an established class of clinically useful medicinal agents possessing antifungal, antibacterial, antiviral and anticancer activity. This has led to our interest in the search for a synthesis of new nucleoside molecule i.e., thymidine analogues that may be screened for broad-spectrum biological activity. Thymidine analogues, containing heterocyclic systems, are known to possess various therapeutic activities for the treatment of human diseases. Thymidine analogues such as telbibudine (thymidine -L-nucleoside analogue), AZT (3 -azido-2 ,3 -dideoxythymidine), stavudine, zalcitabine are being used as antiviral, and HIV, drugs. In our present investigation, four new series of nucleoside derivatives were synthesized from thymidine (1) via only two-step reactions by direct acylation method and furnished the 5 -O-acyl thymidine derivatives in good yields. To obtain newer products for antimicrobial evaluation studies, the 5 -O-thymidine derivatives were further transformed into two series of 2 ,3 -di-O-acyl derivatives (scheme 1-4) containing a wide variety of functionalities in a single molecular framework.