Synthetic analogues of polynucleotides. Part XII. Synthesis of thymidine derivatives containing an oxyacetamido- or an oxyformamido-linkage instead of a phosphodiester group

Abstract

The dinucleotide analogue thymidinylacetamido-[3′(O)→ 5′(C)]-5′-deoxythymidine was synthesised. The compound showed a hypochromic effect of about 10% at 268 nm. At pH 6·0–7·5 and 20° the compound was stable; in M-sodium hydroxide at 37° it was 50% hydrolysed after 3·4 h. 5′-Azido-5′-deoxythymidine was converted into its 3′-O-carboxymethyl derivative and this was reduced to give 5′-amino-3′-O-carboxymethyl-5′-deoxythymidine. Attempts to polymerise this compound were unsuccessful because of the ready formation of a lactam. Thymidinylformamido-[3′(O)→ 5′(C)]-5′-deoxythymidine was also synthesised. It showed a hypochromic effect of about 8% at 267 nm and was more stable to alkali than the acetamido-compound.