A Practical and Efficient Total Synthesis of Potent Insulinotropic (2S,3R,4S)-4-Hydroxyisoleucine through a Chiral N-Protected gamma-Keto-alpha-aminoester
Fiche publication
Date publication
juillet 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WAGNER Alain
Tous les auteurs :
Marin SD, Catala C, Kumar SR, Valleix A, Wagner A, Mioskowski C
Lien Pubmed
Résumé
(2S,3R,4S)-4-Hydroxyisoleucine, which exhibits remarkable insulinotropic activity, is expected to be a potent drug to treat type II diabetes. We propose herein a four-step synthesis of the enantiopure natural product on the basis of successive Mannich condensation, catalytic epimerization, N-paramethoxyphenyl deprotection, and diastereoselective reduction. This compact economical and scalable sequence enables to perfectly control three contiguous chiral centers, It does not involve any chromatographic purification, and the desired compound is obtained in >99 %de, >99 % ee, and 22% overall yield under our optimized conditions.
Référence
Eur J Org Chem. 2010 Jul;21:3985-9