Peptides; receptor agonists; NMR; circular dichroism; molecular modeling

The syntheses of the 2′-deoxy and 2′,3′-dideoxynucleosides of 2,8-diaza-3-deazainosine and the 2′,3′-dideoxynucleoside of 2-aza-3-deazainosine were achieved and the pathways leading to these novel nucleosides are described. The preparation of the 2′,3′-dideoxynucleoside () of 2-aza-3-deazainosine involved deoxygenation of the 2′-deoxy-3′-imidazolide intermediate with n-Bu3SnH and AIBN. The latter nucleoside was synthesized from the known 2′-deoxy derivative of 2-aza-3-deazainosine. The three-step synthesis of from the 2′-deoxy analogue was accomplished in 40% overall yield. Rather than synthesize the corresponding 2′,3′-dideoxynucleoside () of 2,8-diaza-3-deazainosine in the same manner, i.e. deoxygenation of the 2′-deoxynucleoside, a more cost-effective route was chosen. This pathway involved reductive cleavage of the 5′-protected, 2′,3′-thiocarbonate derivative to furnish a mixture of the 2′- and 3′-deoxy isomers. This mixture was not separated, but was deoxygenated by the aforementioned imidazolide method. Using this methodology, was prepared in 23% overall yield from 2,8-diaza-3-deazainosine. Nucleosides and were evaluated for antiretroviral activity and were found to be inactive.