A synthesis of Entecavir (BMS-200475) was achieved starting from 1,3-propanediol in 15 steps and 23.4% overall yield. A unique feature of the synthetic route is that the five-membered carbocyclic core is installed by an intramolecular nitrile oxide cycloaddition (INOC) reaction and the guanine moiety is introduced by a Mitsunobu reaction. The route is characteristic of low cost, high yield and easy operation.