Stereoselective synthesis of original spirolactams displaying promising folded structures.

Guilhem Chaubet (1) , Thibault Coursindel (1) , Xavier Morelli (2) , Stéphane Betzi (2) , Philippe Roche (2) , Yannick Guari (3) , Aurélien Lebrun (1) , Loïc Toupet (4) , Yves Collette (2) , Isabelle Parrot (1) , Jean Martinez (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 CRCM - Centre de Recherche en Cancérologie de Marseille
3 ICGM ICMMM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
4 IPR - Institut de Physique de Rennes

Access to diastereoisomeric forms of original spirolactam frameworks and investigation of their folded potentials are depicted here. Taking advantage of a stereoselective ring-contraction reaction, the Transannular Rearrangement of Activated Lactams (TRAL), followed by two unprecedented tandem reactions, we describe here an efficient access to elegant spirocyclic scaffolds. After dimerization, NMR analyses, circular dichroism, SEM and molecular modelling indicated the existence of an attractive edifice able to fold and behave as a PPII helix, a common yet neglected peptidic secondary structure.

Domaines: Chimie organique

Guilhem Chaubet, Thibault Coursindel, Xavier Morelli, Stéphane Betzi, Philippe Roche, et al.. Stereoselective synthesis of original spirolactams displaying promising folded structures.. Organic & Biomolecular Chemistry, 2013, 11 (28), pp.4719-26. ⟨10.1039/c3ob40643a⟩. ⟨hal-00871067⟩