Fiche publication
Date publication
décembre 2020
Journal
The Journal of organic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARNIER Delphine
Tous les auteurs :
Tang SQ, Leloire M, Schneider S, Mohr J, Bricard J, Gizzi P, Garnier D, Schmitt M, Bihel F
Lien Pubmed
Résumé
Herein, we report the diastereoselective synthesis of a 3-amino-1,2,4-oxadiazine (AOXD) scaffold. The presence of a N-O bond in the ring prevents the planar geometry of the aromatic system and induces a strong decrease in the basicity of the guanidine moiety. While DIBAL-H appeared to be the most efficient reducing agent because it exhibited high diastereoselectivity, we observed various behaviors of the Mitsunobu reaction on the resulting β-aminoalcohol, leading to either inversion or retention of the configuration depending on the steric hindrance in the vicinity of the hydroxy group. The physicochemical properties (p and log ) and hepatic stability of several AOXD derivatives were experimentally determined and found that the AOXD scaffold possesses promising properties for drug development. Moreover, we synthesized alchornedine, the only natural product with the AOXD scaffold. Based on a comparison of the analytical data, we found that the reported structure of alchornedine was incorrect and hypothesized a new one.
Référence
J Org Chem. 2020 12 4;85(23):15347-15359
