Nucleotides. Part LVI. Synthesis and biological activity of modified (2′–5′)triadenylates containing 2′‐terminal 2′,3′‐dideoxy‐3′‐fluoroadenosine derivatives

Some new (2′–5′)triadenylates 13–16, containing at the 2′-terminal end 3′-fluoro-2′,3′-dideoxyadenosine derivatives, have been synthesized by the phosphotriester method. The selectively blocked nucleosides 2, 4, 5, and 7, were synthesized from the corresponding unprotected nucleosides 1, 3, and 6. The synthesized trimers 13, and 14 were 4- and 8-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the natural trimer 17. In comparison to trimer 17 the new compounds 13–15 inhibit HIV-1 reverse transcriptase (RT) activity, and 15 and 16 the HIV-1 induced syncytia formation 2–3 fold whereas none of 13–16 can improve R Nase L activity.