Synthetic analogues of polynucleotides. Part 15. The synthesis and properties of poly(5′-amino-3′-O-carboxymethyl-2′,5′-dideoxy-erythro-pentonucleosides) containing 3′(O)→ 5′(C) acetamidate linkages

Abstract

Poly(5′-amino-3′-O-carboxymethyl-5′-deoxythymidine) was prepared by the polymerisation of 5′-chloroacetamido- 5′-deoxythymidine under basic conditions to give a polymer which contained in addition to 3′(O)→5′(C) acetamidate linkages, a substantial proportion of 3′(O)→3-acetamidate linkages. To obtain a polymer which contains 3′(O)→ 5′(C) linkages, 5′-amino-5′-deoxythymidinylacetamido[3′(O)→ 5′(C)]·5′-deoxythymidin-3′-ylacetic acid (7) was synthesised and polymerised. Compound (7) was obtained by the reduction of the corresponding 5′-azido compound. The latter was obtained by the condensation of the pentachlorophenyl ester of 5′-azido-3′-O-carboxymethyl-5′-deoxythymidine with 5′-amino-3′-O-carboxymethyl-5′-deoxythymidine. Poly (5′-amino -3′-O-carboxymethyl-2′,5′-dideoxycytidine) was obtained by the polymerisation of 4-N-acetyl-5′-chloroacetamido-2′.5′-dideoxycytidine (10) under basic conditions followed by removal of the 4-N-acetyl groups by mild acidic hydrolysis. This polymer contained 3′(O)→ 5′(C) acetamidate linkages and probably <6% of other acetamidate linkages. Compound (10) was obtained from the corresponding 5′-p-tolylsulphonyloxy compound via the 5′-azido compound. None of these polymers showed any evidence of base stacking or of interaction with their complementary polyribonucleotides.