Synthesis and Enantioselective Transformation of a New Series of Pharmacologically Important 4-Aryl-1, 4-Dihydropyridines By Microbial Lipases

Dihydropyridines are the most important class of calcium antagonists having broad range of pharmaceutical and therapeutic effects. Second generation dihydropyridines possess at least one chiral centre and the effects differ from one enantiomer to the other. The other enantiomer of the drug is many a times an antagonist, leading to serious side effects upon administration. The present work describes the synthesis of new series of 4-aryl-1, 4-dihydropyridines. Microwave assisted synthesis of different dihydropyridine analogues have been studied in our laboratory, offering distinct advantages of shorter reaction time and avoiding hazardous solvents. The compounds so obtained were analysed via NMR, IR and MS for structure elucidation. These compounds were screened in terms of wavelength, temperature and eluent composition to resolve the components in the shortest time. These racemic analogues were then resolved on a Chiralcel ODH column of HPLC. The wavelength so chosen is based on the substantial absorption by the compound possessing the best S/N ratio. This was first assayed with a mobile phase comprising of n-hexane and isopropanol in different proportions between 22 to 30^oC. The racemic analogues were resolved best at 353nm with a retention time of less than 10 minutes. Further the stereo selective biotransformations have been investigated on these racemic analogues using Candida antarctica lipase. The optical rotation values were measured using polarimeter. The non-zero values for the optical rotation confirms the enantioselective hydrolysis. The optical yields and optical configurations are being investigated by HPLC where an enantiomeric access of 65-70% has been attained.