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Improved Large‐Scale Liquid‐Phase Synthesis and High‐Temperature NMR Characterization of Short (F‐)PNAs
Author(s) -
Plöger Tobias A.,
von Kiedrowski Günter
Publication year - 2011
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201100243
Subject(s) - trimer , chemistry , oligomer , coalescence (physics) , solubility , nmr spectra database , proton nmr , pentamer , spectral line , nuclear magnetic resonance spectroscopy , phase (matter) , acetic acid , crystallography , stereochemistry , organic chemistry , dimer , biochemistry , physics , astronomy , astrobiology
We report on a large‐scale synthesis of F‐PNA trimer 10 and PNA trimer 11 . The key improvement is the facile two‐step synthesis of (2,4‐difluoro‐5‐methylphenyl)acetic acid ( 2 ). Water solubility of the corresponding F‐PNA oligomer 10 was achieved by synthesizing solubility enhancer 5a , which is twofold positively charged and only consists of inherent structural elements of PNA. Protected and unpaired PNA n ‐mers exist in a mixture of 2 n conformers undergoing slow exchange and leading to complicated NMR spectra. Structure analysis was improved by recording 1 H‐ and 13 C‐NMR spectra at elevated temperatures above the coalescence point. Fully protected backbone derivatives show sharp resonances where expected, and spectra of protected PNAs are remarkably simplified, thereby allowing an interpretation for the first time. Both trimers 10 and 11 are considered as building blocks for a self‐replicating system based on PNA.