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

Article abstract of DOI:10.1002/hlca.19950780711

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.