Synthèse à grande échelle de molécules cages énantiopures : propriétés chiroptiques et de reconnaissance

The design of chiral molecular containers is very attractive because they can mimic biological systems such as enzymes. However, the synthesis of such sophisticated chiral structures is highly challenging, and methods to obtain suitable amounts of enantiopure molecular cages in a few steps have still to be developed. Thus, the discovery of an easy access to large quantities of enantiopure hemicryptophane cages should strongly promote their application in chiral recognition or asymmetric supramolecular catalysis.

Fig.1

A convenient and efficient gram-scale synthesis for enantiopure hemicryptophane–tren (tren=tris(2-aminoethyl)amine) derivatives has been developed. The four-step synthesis is based on the optical resolution of a key intermediate, cyclotriveratrylene, for which the energy barrier for racemization has been measured to ensure that no racemization occurs during the two last steps of the synthetic pathway. The assignments of the absolute configurations have been performed by electronic circular dichroism (Fig.1) and the enantiopurity was determined by NMR spectroscopy in the presence of enantiopure camphor sulfonic acid. To highlight the interest of such compounds, the recognition of norephedrine neurotransmitter was investigated and showed a remarkable enantioselectivity towards the C3 symmetrical hosts. Finally, this highly modular synthetic pathway was used to provide eight enantiopure hemicryptophanes with different sizes, shapes, and functionalities. These results underline the high potential of this approach, which could lead to many applications in chiral recognition or asymmetric supramolecular catalysis.

Large-Scale Synthesis of Enantiopure Molecular Cages: Chiroptical and Recognition Properties
Lefevre, S ; Zhang, DW  ; Godart, E ; Jean, M ; Vanthuyne, N  ; Mulatier, JC ; Dutasta, JP ; Guy, L ; Martinez, A
CHEMISTRY-A EUROPEAN JOURNAL, 2016, Volume: 22, Issue: 6, Pages: 2068-2074
DOI: 10.1002/chem.201504108