An Efficient Chemoenzymatic Route towards Biologically Active Pyridinic Amines

Starting from the easily prepared 1-(pyridin-2-yl)- or 1-(4-chloropyridin-2-yl)ethan-1-ones bearer of different substituents (cyclohexyl, phenyl, pyridin-2-yl) in the position 2, the corresponding primary pyridinic ethanamines have been synthesized in very high enantiomeric excesses (ee ≥ 97%). The strategy involves a highly enantioselective ketoreductase (KRED) catalyzed reduction, mesylation of the resulting optically active alcohol followed by nucleophilic substitution with azide anion and, finally, reduction of the azide function. Some of these pyridinic amines obtained in such manner are precursors of biologically active compounds such as Ontazolast.