AbstractNovel 2'(β)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2-propanone-1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbruggen conditions. Condensationof aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleosidephosphonate analogues 15. Ammonolysis and hydrolysis of phosphonates gave the nucleoside phosphonic acid analogue17 and 19. The synthesized nucleoside analogues were subjected to antiviral screening against HIV-1. The adenineanalogue 19 exhibited weak in vitro activities against HIV-1.Key word: Anti-HIV Agents, 2'-Methyl-5'-deoxyphosphonic Acid Analogue, Vorbruggen Reaction 1. Introduction Nonclassical nucleosides continue to be a promisingchallenge for the development of new antiviral agentssince the discovery of lamivudine as anti-human immu-nodeficiency virus (HIV) and anti-hepatitis B virus(HBV) agent [1] . The apio dideoxynucleoside also belongto the class of nonclassical nucleoside in that 4-hydroxymethyl of the 2.3-dideoxyribose moves to theC3 position. This class of nucleosides like (1) (Figure1) showed not only the antiviral activity, but also met-abolic advantage such as resistance to adenosine deam-inase and glycosyl bond hydrolysis, when compared tothe classical 2,3-dideoxynucleosides