Nucleotides. Part XLV. Synthesis of new (2′–5′)adenylate trimers, containing 5′‐amino‐5′‐deoxyadenosine residues at the 5′‐end of the oligoadenylate chain, and of its analogues, carrying a 9‐[(2‐hydroxyethoxy)methyl]adenine residue at the 2′‐terminus

The 5′‐amino‐5′‐deoxy‐2′,3′‐O‐isopropylideneadenosine (4) was obtained in pure form from 2′,3′‐O‐isopropylideneadenosine (1), without isolation of intermediates 2 and 3. The 2‐(4‐nitrophenyl)ethoxycarbonyl group was used for protection of the NH2 functions of 4 (→7). The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′‐N‐position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et3N (→5). The 3′‐O‐silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′‐O‐deprotected compounds 8 and 9, respectively, with (tert‐butyl)dimethylsilyl chloride and 1H‐imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14, respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH2Cl2. The trimeric (2′–5′)‐linked adenylates 25 and 26 having the 5′‐amino‐5′‐deoxyadenosine and 5′‐deoxy‐5′‐(palmitoylamino)adenosine residue, respectively, at the 5′‐end were prepared by the phosphoramidite method. Similarly, the corresponding 5′‐amino derivatives 27 and 28 carrying the 9‐[(2‐hydroxyethoxy)methyl]adenine residue at the 2′‐terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25–28 were 3‐, 15‐, 25‐, and 34‐fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′–5′)ApApA.