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 (U-1-PNA) with several terminal alkynes. These reactions hake been performed in the solution Phase and with U-1-PNA linked to an insoluble polymer Support. The results presented herein shock 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 LIS 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 U-1 insert is given. (C) 2002 Elsevier Science Ltd. All rights reserved.