Synthesis of N-alpha-(purinyl/pyrimidinyl acetyl)-4-aminoproline diastereomers with potential use in PNA synthesis

This paper describes an approach to introduce conformational constraint and chirality into the PNA backbone by bridging the ethylenediamine and glycine components of the same unit by a methylene group which leads to PNA based on 4-aminoprolyl backbone with chirality at C-4 and C-2. The synthesis and characterisation of all four diasteroisomers with thymine (T) as the sidechain nucleobase (3a-d) and the synthesis of one of the stereoisomer (2S, 4R) linked to each of the four nucleobases (10-13) are described. Using these monomeric units, two model dimers (17, 18) containing four chiral centres but differing in stereochemistry at only one site were prepared and CD data on these indicate considerable structural differences in base stacking induced by chiral backbone among these. Copyright (C) 1996 Elsevier Science Ltd