title: Combinatorial aid for underprivileged scaffolds: solution and solid-phase strategies for a rapid and efficient access to novel aza-diketopiperazines (Aza-DKP).
abstract: 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.
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS, Université de Strasbourg , Faculté de Pharmacie, 74 route du Rhin, 67412 Illkirch, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Margathe
authors.forename: Sally
authors.initials: S
authors.lastname: Radford
authors.forename: Elsa
authors.initials: E
authors.lastname: Pflimlin
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Riché
authors.forename: Pete
authors.initials: P
authors.lastname: Doman
authors.forename: Marcel
authors.initials: M
authors.lastname: Hibert
authors.forename: A
authors.initials: A
authors.lastname: Ganesan
mesh_terms: D001372:Aza Compounds / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: D001372:Aza Compounds; D054659:Diketopiperazines