[The influence of steric crowding on the electrochemical reduction of amide groups in a pyridylcarboxamide seriesapplication to rote ction of amines in peptide synthesis].
To gain a better understanding of the effect exerted by the 3-hydroxypicolinoyl residue on the antibiotic activity of Pristinamycin IA, the C-N bond of picolinamide was cleaved electrochemically. A mechanistic study demonstrated that the presence of the peptidic macrolactone M markedly modified the expected cathodic behavior of pyridylcarboxamides. In order to assess the influence of steric crowding exerted by M on this original behavior, we look for models using two different approachs. First, tertiary pyridylcarboxamides were used to increase steric hindrance at the amide nitrogen position; second, M was opened by ammonolysis to decrease steric crowding at the amide nitrogen position. The electrochemical behavior of the selected compounds is presented in the first and the second parts of this study. Determination of pyridine nitrogen basicity in an N-substituted-3-methoxypicolinamide series is treated in the third part as a useful probe to evaluate the intensity of steric crowding at the amide nitrogen position. Finally, in the last part of this work, we propose the use of the picolinoyl residue (C6H4N-CO-ou Pic) as a protecting group for amines in peptide synthesis.
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Université René Descartes, Paris.
D000577:Amides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D004563:Electrochemistry; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D014769:Virginiamycin / Q000138:chemical synthesis / Q000737:chemistry
D000577:Amides; D000900:Anti-Bacterial Agents; D010455:Peptides; D011725:Pyridines; D014769:Virginiamycin
Incidence de l'encombrement stérique sur la réduction électrochimique du groupement amide en série pyridylcarboxamide: application à la protection des amines en synthèse peptidique.