An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (-)- and racemic isomers.
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