Synthesis and evaluation of anti-HIV-1 activity of 3′-azido-3′-deoxy-2′-O,4′-C-methylene-linked bicyclic thymine nucleosides

Abstract

The two conformationally locked AZT analogues 4 and 5, each containing a 2′-O,4′-C-methylene-linked bicyclic furanose moiety, are synthesized via the 3′-azido-3′-deoxy-4′-C-hydroxymethyl nucleoside 16. The β-D-ribo-configured derivative 4 is shown by NOE experiments to exist in a north-type (³E, C3′-endo) conformation and the α-L-xylo-configured derivative 5 in a south-type (₃E, C3′-exo) conformation. Both nucleosides were devoid of anti-HIV activity in MT-4 cells.