Solid Phase Synthesis of Helically Folded Aromatic Oligoamides
Résumé
Aromatic amide foldamers constitute a growing class of oligomers that adopt remarkably stable folded conformations. The folded structures possess largely predictable shapes and open the way towards the design of synthetic mimics of proteins. Important examples of aromatic amide foldamers include oligomers of 7- or 8-amino-2-quinoline carboxylic acid that have been shown to exist predominantly as well-defined helices, including when they are combine with -amino acids to which they may impose their folding behavior. To rapidly iterate their synthesis, solid phase synthesis protocols have been developed and optimized for overcoming synthetic difficulties inherent to these backbones such as low nucleophilicity of amine groups on electron poor aromatic rings and a strong propensity of even short sequences to fold on the solid phase during synthesis. For example, acid chloride activation and the use of microwaves are required to bring coupling at aromatic amines to completion. Here, we report detailed solid phase synthesis protocols for the rapid production of: 1) oligomers of 8-amino-2-quinolinecarboxylic acid; 2) oligomers containing 7-amino-8-fluoro-2-quinolinecarboxylic acid; 3) heteromeric oligomers of 8-amino-2-quinolinecarboxylic acid and -amino acids. Solid phase synthesis brings the advantage to quickly produce sequences having varied main chain or side chain components without having to purify multiple intermediates as in solution phase synthesis. With these protocols, an octamer could easily be synthesized and purified within one to two weeks from Fmoc protected amino acid monomer precursors.
Domaines
Chimie
Origine : Fichiers produits par l'(les) auteur(s)
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