Synthesis of optically active copoly(vinylamine-vinylalcohol) containing a pair of adeninyl and thyminyl pendant groups

Preparation of novel model polymers of polynucleotides with copoly(vinylamine–vinylalcohol) [P(Vam–Val)] backbone and a pair of adeninyl and thyminyl pendant groups is described. At first, direct, low temperature esterification was used to attach (−) and (±)‐2‐(thymin‐1‐yl)propionic acid [(−)TPA and (±)TPA], to the N–Cbz protected hydroxy polymer P(Vamz–Val) which was prepared by selective N‐protection of N‐benzyloxycarbonyloxy‐5‐norbornene‐2,3‐dicarboximide (CbzONB) with P(Vam–Val), at the hydroxy group via an ester bond. Two novel precursors P(Vamz–Ve(−)T) and P(Vamz–Ve(±)T) were obtained. Then the Cbz protecting group of P(Vamz–Ve(−)T) and P(Vamz–Ve(±)T) were removed by hydrobromic acid to give the hydrobromide salt of P(Vam–Ve(−)T) and P(Vam–Ve(±)T), respectively. Finally, the attachment of (±)‐2‐(adenine‐9‐yl)propionic acid [(±)APA] to linear P(Vam–Ve(−)T) and P(Vam–Ve(±)T) by selective N‐acylation with N‐hydroxy‐5‐norbornene‐2,3‐dicarboximide (HONB). This procedure gave the corresponding P(Vam–Val) having a pair of adeninyl and thyminyl pendant groups, such as P(Va(±)Ad–Ve(−)T) and P(Va(±)Ad–Ve(±)T). In contrast to the corresponding polymer models, the related segment model compounds were also prepared from threo‐2‐amino‐4‐pentanol without N‐blocking‐deblocking operations. The segment model compounds including four stereoisomers of highly optical purities, were separated and purified by reverse phase HPLC technique.