Synthesis of novel 3′-C-methyl-apionucleosides: an asymmetric construction of a quaternary carbon by Claisen rearrangement Original Research Article

The synthesis of 2,3-dideoxy-3-C-(hydroxymethyl)-3-C-methyl-d-glycero-tetrofuranosyl nucleosides was accomplished in high enatiomeric purity (98.5% ee) via [3,3]-sigmatropic Claisen rearrangement of (E)(S)-5-benzyloxy-1-tert-butyldimethylsilanyloxy-4-methyl-pent-3-en-2-ol prepared from 2,3-O-isopropylidene-d-glyceraldehyde. The synthesized nucleosides were assayed against human immunodeficiency virus (HIV) and hepatitis B virus in human peripheral blood mononuclear (PBM) and 2.2.15 cells, respectively. 6-Amino-9-[2,3-dideoxy-3-C-(hydroxymethyl)-3-C-methyl-β-d-glycero-tetrofuranosyl]-2-fluoropurine shows moderate antiviral activity (EC50=2.55 μM) against HIV-1 strains and 6-amino-9-[3-deoxy-3-C-(hydroxymethyl)-3-methyl-α-d-glycero-tetrofuranosyl]-2-fluoropurine exhibits potent anti-HIV activity (EC50=0.073 μM) with significant cytotoxity (IC50=1.0 μM).