An expeditious liquid-phase synthesis of cyclic peptide nucleic acids

Suitably protected linear precursors of cyclic PNAs can be readily obtained by BOP/DiPEA coupling of the corresponding sub-monomers. Conversion of the linear PNA dimers into the pentafluorophenyl esters allows cyclization by intramolecular attack of the deprotected primary amino function under diluted conditions. After removal of the secondary amino protecting group(s), installation of the required nucleobase-acetyl function(s) affords cyclic PNAs. In addition, the latter compounds can be prepared following a direct coupling strategy.