Synthetic analogues of polynucleotides. Part V. Analogues of trinucleoside diphosphates containing carboxymethylthymidine

Abstract

Analogues of trinucleoside diphosphates in which the nucleoside units are linked by acetate ester linkages (·O·CH₂·-CO₂·), instead of the phosphodiester linkages of the natural compounds, have been synthesised. 3′-O-Carboxy-methyl-5′-O-tritylthymidine was condensed with the 2-cyanoethyl ester of 3′-O-carboxymethylthymidine to give a compound in which two thymidine residues were linked by an acetate ester linkage (II; R¹= trityl, R²= CH₂·-CH₂·CN). The cyanoethyl group was selectively removed with potassium t-butoxide in dimethylformamide and the resulting carboxylic acid was condensed with 2′,3′-O-isopropylidene- or 2′,3′-O-anisylidene-ribonucleosides to give, after removal of the acid-labile protecting groups, thymidinylacetyl-(3′→ 5′)-thymidinylacetyl-(3′→ 5′)-ribonucleosides (III; R¹= R²= R³= H), where the ribonucleosides were adenosine, uridine, guanosine, inosine, and cytidine. Evidence for base stacking in these analogues was obtained by u.v. and n.m.r. spectroscopy.