1-(2,3,4-tri-O-acety-6-azido-6-deoxy-5-thio-b-D-glucopyranosyl)thymine 5 and the 6-thio-septanosylthymine analogue 7 were obtained via the intramolecular displacement of the corresponding tosylate 2 by azide. Alternatively, 5 was obtained from bromination of alcohol 1 in the presence of azide. Deblocking of 5 afforded the nucleoside 6. Glycosylation of the tetraacetate 11, obtained by acetolysis of 10 with thymine, afforded the 3-O-tosyl-b-D-glucopyranosylthymine derivative 13, which furnished the 3-azido-3-deoxy-b-D-allopyranosyl-thymine analogue 14 on reaction with azide ion. Alternatively, the glucoside 12 gave the corresponding gluco analogue 16 on treatment with azide. Acetolysis of 16 furnished the tetraacetate 17, which was subjected for glycosylation to give the gluco nucleoside 18. Deblocking of 14 and 18 afforded the free 3-azido-nucleosides 15 and 19, respectively. The isothionucleoside 21 was prepared from treatment of thymine with the 2,3-epoxide derivative 20 in the presence of Ti(i-PrO) 4 and triethyl amine. Mild acid hydrolysis of 21 afforded 22. Cycloaddition of the 2-azido-altroside 23 with dimethyl acetylenedicarboxylate gave the 1,2,3-triazole derivative 24. Treatment of 24 with methanolic ammonia afforded the 4,5-carboxamide analogue 25. The conformations of the new products were studied by NMR spectroscopy.

New derivatives of azidothymidine (AZT) substituted by alkyl and alkylsulphonyl groups at N-3 and C-5', respectively, have been synthesized. The new synthesized derivatives showed remarkable anti-HIV-1 and HIV-2 activity in MT-4 cells. Compounds 8 and 10 have IC(50) values of 0.83 and 0.31 microg/mL against HIV-1 with therapeutic index of 83 and 403, respectively, and IC(50) values of 0.93 and 0.29 microg/mL against HIV-2 with therapeutic index of 74 and 431, respectively. This means that compounds 8 and 10 were cytotoxic to MT-4 cells at CC(50) of 69.2 microg/mL and 125 microg/mL, respectively.

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Microwave-assisted synthesis of novel acyclic C-nucleosides of 6-alkyl/aryl-3-(1,2-O-isopropylidene-D-ribo-tetritol-1-yl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (5-12) and the 6-aryl-thiomethyl analogues 25-27 has been described. Deblocking of 5-12 and 25-27 afforded the free acyclic C-nucleosides 13-20, and 28-30, respectively. All of the synthesized compounds showed no inhibition against HIV-1 and HIV-2 replication in MT-4 cells. However, 6-(3,4-dichlorophenyl)-3-(1,2-O-isopropylidene-D-ribo-tetritol-1-yl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (6) is a potent inhibitor, in vitro, of the replication of HIV-2. These results suggest that compound 6 should be considered as a new lead in the development of antiviral agent.

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