NUCLEOTIDES .45. SYNTHESIS OF NEW (2'-5')ADENYLATE TRIMERS, CONTAINING 5'-AMINO-5'-DEOXYADENOSINE RESIDUES AT THE 5'-END OF THE OLIGOADENYLATE CHAIN, AND OF ITS ANALOGS, CARRYING A 9-[(2-HYDROXYETHOXY)METHYL]ADENINE RESIDUE AT THE 2'-TERMINUS

• Published in: Helvetica chimica acta Vol. 78; no. 7; pp. 1777 - 1784
• Main Authors: KVASYUK, EI, KULAK, TI, MIKHAILOPULO, IA, CHARUBALA, R, PFLEIDERER, W
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.01.1995
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; OLIGONUCLEOTIDES
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.19950780711

The 5'-amino-5'-deoxy-2', 3'-0-isopropylideneadenosine (4) was obtained in pure form from 2',3'-0-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 Et(3)N (-->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.