Nucleotides. Part. XXXII. Synthesis of 2′–5′ Connected oligonucleotides. Prodrugs for antiviral and antitumoral nucleosides

The cytotoxically and antivirally active compounds bvU_d ( 1 ), flU_d ( 4 ), acyclovir ( 7 ), and A_a ( 12 ) have chemically been combined with the appropriately protected (2′–5′)diadenylate 20 by the phosphotriester approach to give the 2′–5′ oligonucleotide trimers 21 – 24 . The deprotection of the various blocking groups by chemical means afforded the 2′–5′ trimers 25 – 28 , which can be regarded as new type of a potential prodrug form delivering nucleotides to the targets inside cells. In an analogous series of reactions, 9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine was coupled with 7 to the 2′–5′ trimer 31 . The antiviral screening of the oligonucleotides 25–27 and 31 showed biological activities closely related to the parent nucleosides, possibly indicating their release by enzymatic cleavage of the oligomers.