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Accueil > Équipes de recherche > Pharmacognosie - Chimie des Substances Naturelles > Nos livres ou articles en couvertures > Thermodynamic epimeric equilibration and crystallisation-induced dynamic resolution of lobelanine, norlobelanine and related analogues

Thermodynamic epimeric equilibration and crystallisation-induced dynamic resolution of lobelanine, norlobelanine and related analogues

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Organic & Biomolecular Chemistry : Thermodynamic epimeric equilibration and crystallisation-induced dynamic resolution of lobelanine, norlobelanine and related analogues

Z. Amara, G. Bernadat, P.-E. Venot, P. Retailleau, C. Troufflard, E. Drège, F. Le Bideau and D. Joseph

The step-economical synthesis of lobelanine involving a ring closing double aza-Michael (RCDAM) reaction is revisited and successfully extended to the synthesis of various configurationally more stable analogues. Owing to the presence of a configurationally labile β-aminoketone subunit, lobelanine is prone to self-catalyze mutarotation in solution. Through the synthesis of original lobelanine analogues, we studied the influence of (i) the size of the central heterocycle, (ii) the bulkiness of the nitrogen protect- ing group, and (iii) the phenacyl arm substituent on the thermodynamic equilibrium and its displacement by crystallisation-induced dynamic resolution (CIDR). We demonstrated that fine structural tuning com- bined with optimized CIDR conditions favours the first efficient diastereoselective synthesis of lobelanine’s analogues.

Organic & Biomolecular Chemistry : Thermodynamic epimeric equilibration and crystallisation-induced dynamic resolution of lobelanine, norlobelanine and related analogues