Improvements in automated PNA synthesis using Boc/Z monomers

Abstract
An optimized automated PNA synthesis protocol is reported. Under optimal conditions the product yield of a test 17-mer PNA is approximately 90%. The average coupling yield is 99.4%. The synthesis strategy is Boc/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 delivery 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 μmol scale but is easily scaled up to 10–50 μmol scale syntheses on the automated synthesizer (ABI 433A). © Munksgaard 1997.

This publication has 31 references indexed in Scilit: