Synthesis of oxathiolane imidazole nucleosides.

Nucleosides have been of great interest since their strong antiviral activities were discovered. 1,3-Oxathiolane ring system has been known for many years, but it is in recent years that the ring has been used as the sugar ring in nucleoside analogs (Synthesis (1991) 1046; J. Am. Chem. Soc. 113 (1991) 9377; Tetrahedron Lett. 35 (1994) 4739). Besides, bredinin is a natural nucleoside antibiotic with imidazole moiety and there are some other studies reported on nucleosides with the imidazole group (Biorg. Med. Chem. 7 (1999) 481; Biorg. Med. Chem. 7 (1999) 1617; Nucleosides Nucleotides 18 (1999) 331). These findings make the imidazole group interesting as the base of a nucleoside. In this study, in order to find out the structure-activity relationships of L-oxathiolanyl nucleosides, L-oxathiolanyl imidazole nucleosides 7 and 8 were synthesized, via novel intermediates 2-6, which were then tested for anti-HIV activity (Antivir. Res. 1-11 (1994) 25) in human peripheral blood mononuclear (PBM) cells, the synthesized nucleosides did not show significant activity up to 100 microM against HIV-1.