Abstract A novel 2', 4'-dimethyl carbocyclic adenosine 5'-phosphonic acid analogue (20) was prepared using acyclic stereoselective route from commercially available 4- hydroxybutan-2-one (4). To improve cellular permeability and enhance the anti-HCV activity of this phosphonic acid, a 3', 5'-cyclic SATE phosphonodiester nucleoside prodrug (22) was prepared. The synthesized phosphonic nucleoside analogues,(20) and (22), were ...