SYNTHETIC ANALOGS OF POLYNUCLEOTIDES .15. SYNTHESIS AND PROPERTIES OF POLY(5'-AMINO-3'-O-CARBOXYMETHYL-2',5'-DIDEOXY-ERYTHRO-PENTONUCLEOSIDES) CONTAINING 3'(O)-]5'(C) ACETAMIDATE LINKAGES

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.