Unconventional nucleotide analogues. Part X. Synthesis of N-substituted 3-(adenin-9-yl)pyrrolidin-2-ones

Abstract

3-(Adenin-9-yl)-N-2-hydroxyethylpyrrolidin-2-one (1) was synthesized by constructing the purine base on the amino-group of 3-amino-N-2-hydroxyethylpyrrolidin-2-one (3), itself obtained from 2-dibenzylaminobutyro-lactone by aminolysis, followed by chlorination of the product and recyclization. Attempts to obtain compound (3) from acylated 2-aminobutyrolactones (4a and b) led to side reactions, the mechanisms of which are discussed. 3-(6-Chloropurin-9-yl)-N-2-hydroxyethylpyrrolidin-2-one (18b) was converted into the AMP analogue (2) by a phosphorylation–amination–debenzylation sequence, lodination of compound (1), followed by dehydrohalogen-ation of the product led to the N-vinyl derivative (21 ), a monomer for a poly-A model.