Combinatorial aid for underprivileged scaffolds: solution and solid-phase strategies for a rapid and efficient access to novel aza-diketopiperazines (Aza-DKP).
Fiche publication
Date publication
mai 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HIBERT Marcel
Tous les auteurs :
Bonnet D, Margathe JF, Radford S, Pflimlin E, Riche S, Doman P, Hibert M, Ganesan A
Lien Pubmed
Résumé
An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4-triazine-3,6-diones has been synthesized starting from Fmoc-l-Pro-OH and various Fmoc-l-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and (1)H NMR spectroscopy.
Référence
ACS Comb Sci. 2012 May 14;14(5):323-34