1448166-80-0Relevant academic research and scientific papers
Effective method of lipase-catalyzed enantioresolution of 6-alkylsulfanyl-1,4-dihydropyridines
Andzans, Zigmars,Adlere, Ilze,Versilovskis, Aleksandrs,Krasnova, Laura,Grinberga, Signe,Duburs, Gunars,Krauze, Aivars
, p. 43 - 58 (2014/02/14)
A series of 6-alkylsulfanyl-1,4-dihydropyridines (±)-2 bearing a methoxycarbonylethyl group as a mild easily removable protecting group at S atom have been prepared by alkylation of 6-thioxo-1,4-dihydropyridines 1 with methyl bromopropionate. Candida antarctica lipase B (Novozyme 435, CAL-B) - and Amano Acylase (Aspergillus mellus)-catalyzed kinetic resolution has been investigated in water-saturated diisopropyl ether (IPE) at 25 and 45 °C. After acrylic acid methyl ester as leaving group cleavage and alkylation of formed enantioenriched 1,4-dihydropyridine-6-thiolates (-)-4 and (+)-4, optically active 1,4-dihydropyridines (-)-2, (+)-2, (-)-5 and (+)-5 were obtained in 85-99% enantiomeric excess. The experiments present the 6-(methoxycarbonylethyl)- sulfanyl group as an essentially new enzymatically labile (activating) group. The ester group being 6 bonds remote from the chiral center undergoes easy enzymatic hydrolysis and could be used for kinetic resolution of racemic 1,4-DHPs. This developed method offers access to mild optically active nucleophilic tiolates, which could be easily derivatized with electrophilic reagents.
