Fmoc/Acyl protecting groups in the synthesis of polyamide (peptide) nucleic acid monomers

摘要

The chemical synthesis of polyamide (peptide)nucleic acid (PNA) monomers 22-25 has been accomplished using Fmoc [N-(2-aminoethyl)glycine backbone],anisoyl (adenine),4-tert-butylbenzoyl (cytosine) and isobutyryl/diphenylcarbamoyl(guanine) protecting-group combinations, thus allowing oligomer synthesis on both pepetide and oligonucleotide synthesizers. An alternative method for the preparation of (N~6-anisoyladenin-9-yl) acetic acid 7 is described using partial hydrolysis of a dianisoylated derivative. Different methods were studied for guanine alkylation including (a) Mitsunobu reaction;(b)low-temperature,sodium hydride- and (c) N,N-diisopropylethylaminemediated alkylation reaction reactions to give preferentially N~9-substituted derivatives. Empirical rules are proposed for differentiating N~9/N~7-substituted guanines based on their ~(13)C NMR chemical-shift differences.