Comparison of the efficiency of various coupling systems in the acylation of model secondary amines with thymin-1-ylacetic acid.

Peptide nucleic acids (PNAs) make a promising group of DNA analogues. The backbone of typical PNA oligomers is composed of N-(2-aminoethyl)glycine units, linked by the peptide bonds. The backbone secondary amine groups are acylated with carboxyalkyl derivatives of nucleobases. One of the PNA synthesis step causing some problems is the acylation of the monomer backbone with the nucleobase derivatives. The aim of the study was to compare the efficiency of various coupling systems in the acylation. Simple model compounds (piperidine and proline) were used, as well as equimolar amounts of the coupling reagents. Selected systems based on carbodiimides, aminium or phosphonium salts, mixed anhydride, and active esters were tested.