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Aromatic δ-peptides: design, synthesis and structural studies of helical, quinoline-derived oligoamide foldamers

2003; Elsevier BV; Volume: 59; Issue: 42 Linguagem: Inglês

10.1016/j.tet.2003.08.058

1464-5416

Hua Jiang, Jean‐Michel Léger, Christel Dolain, Philippe Guionneau, Ivan Huc,

Antimicrobial Peptides and Activities

Oligoamides of 8-amino-4-isobutoxy-2-quinolinecarboxylic acid were designed and synthesized, and their helical structures were characterized in the solid state by single crystal X-ray diffraction, and in solution by 1H NMR. The monomer methyl 4-isobutoxy-8-nitro-2-quinolinecarboxylate is easily prepared in three steps from 2-nitroaninile and dimethyl acetylene dicarboxylate. Successive hydrogenations of nitro groups, saponifications of esters and couplings of amines and acids via the acid chlorides gave a dimer, tetramer, hexamer, octamer, and decamer in a convergent fashion. The oligomers were shown to adopt a bent conformation stabilized by intramolecular hydrogen bonds between amide hydrogens and adjacent quinoline nitrogens. In the solid, the dimer adopts a planar crescent shape and the octamer a helical conformation. All NMR data are consistent with similar conformations in solution. The helices are apparently remarkably stable. Some of them remain helical even at 120°C in deuterated DMSO. The structural studies confirm the predictions made by computer and demonstrate the high potency of the design principles.