The 5'-amino-5'-deoxy-2',3'-0-isopropylideneadenosine (4) was obtained in pure form from 2',3'-0-isopropylideneadenosine (l), without isolation of intermediates 2 and 3. The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH2 functions of 4 ( 4 7 ) . The selective introduction of the palmitoyl ( = hexadecanoyl) groupinto the 5'-N-position of4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et,N (+ 5). The 3'W-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2',3'-O-deprotected compounds 8 and 9, respectively, with (terf -hutyl)dimethylsilyl chloride and Iff-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14, respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH2CI,. 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 Croralus durissus than the trimer (2-S')ApApA.