Asymmetric synthesis of (R)-nilvadipine and (S)-NB 818 via regioselective bromination of chiral 1,4-dihydropyridines as a key step and enzymatic resolution of racemic 2-hydroxymethyl-1,4-dihydropyridine derivatives

Abstract

Optically active 2-hydroxymethyl-1,4,dihydropyridines were obtained by lipase-catalyzed hydrolysis or transesterification of racemic materials. Chiral NB 818 and nilvadipine have been synthesized from chiral 2- hydroxymethyl-1,4-dihydropyridine. On the other hand, chiral 1,4- dihydropyridines obtained from prochiral substrates have been converted into (S)-NB 818 and (R)-nilvadipine via regioselective bromination of methyl groups under mild conditions.