IMPROVEMENTS IN AUTOMATED PNA SYNTHESIS USING BOC Z MONOMERS/

An optimized automated PNA synthesis protocol is reported. Under optim al conditions the product yield of a test 17-mer PNA is approximately 90%. The average coupling yield is 99.4%. The synthesis strategy is Bo c/Z and the deprotected amine is neutralized in situ. The monomers are added in molar excess to HATU and pre-activated for 60 s before deliv ery to the resin. The concentration of the activated monomers is 0.08 M during the couplings. Heteroselective solvation provides the highest coupling yields, Acetic anhydride is used as capping reagent followed by a piperidine wash. The protocol has been developed in a 5 mu mol s cale but is easily scaled up to 10-50 mu mol scale syntheses on the au tomated synthesizer (ABI 433A). (C) Munksgaard 1997.