Referenced in: none

Automatically associated channels: Kir2.3

Title: Asymmetric synthesis and biological evaluations of (+)- and (-)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels.

Authors: Takashi Yamamoto, Seiji Ohno, Seiji Niwa, Munetaka Tokumasu, Masako Hagihara, Hajime Koganei, Shin-Ichi Fujita, Tomoko Takeda, Yuki Saitou, Satoshi Iwayama, Akira Takahara, Seinosuke Iwata, Masataka Shoji

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Jun 1 , 21, 3317-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21514827

Abstract
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.