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Improvements in automated PNA synthesis using Boc/Z monomers

1997; Wiley; Volume: 49; Issue: 1 Linguagem: Inglês

10.1111/j.1399-3011.1997.tb01124.x

1399-3011

Troels Koch, Henrik F. Hansen, Peter E. Andersen, TINNA LARSEN, H. G. Batz, Kenneth M. Otteson, Henrik Ørum,

DNA and Nucleic Acid Chemistry

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 mumol scale but is easily scaled up to 10-50 mumol scale syntheses on the automated synthesizer (ABI 433A).