The use of Sonogashira coupling for the synthesis of modified uracil peptide nucleic acid

Palladium-catalyzed Sonogashira coupling has been shown to be compatible with PNA monomers as illustrated by the reaction of 5-iodouracil peptide nucleic acid monomer (IU-PNA) with several terminal alkynes. These reactions have been performed in the solution phase and with IU-PNA linked to an insoluble polymer support. The results presented herein show that while the isolated yields from the solution phase chemistry are modest (38–53%), the yields of the resin-bound coupling reactions are essentially quantitative, at the monomer level. A selection of alkynes was used to install various additional functionality on the uracil nucleobase. Examples of a hydroxyl, protected thiol and protected amino group are given. Further, an example of derivatization of a resin-bound oligomer with a single IU insert is given.