Candida rugosa lipase mediated multigram synthesis of acid part of S(+)-atliprofen,a new NSAID and molecular modeling studies aimed at predicting selectivity of the enzyme |
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| Affiliation: | 1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, Sector-67, S.A.S. Nagar, Punjab 160062, India;2. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, Sector-67, S.A.S. Nagar, Punjab 160062, India;3. Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, Sector-67, S.A.S. Nagar, Punjab 160062, India;1. Institute of Marine Biochemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Caugiay, Hanoi, Viet Nam;2. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia;3. Far Eastern Federal University, Suhanova st. 8, Vladivostok 690950, Russia;1. InterBioScreen Ltd, Moscow, 119019, Russia;2. North-Caucasian Zonal Research Veterinary Institute, Novocherkassk 346406, Russia;3. Research Institute of Physical and Organic Chemistry, Southern Federal University, Rostov-on-Don 344090, Russia;1. Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan 316021, People’s Republic of China;2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of China;3. Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, People’s Republic of China;1. Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China;2. Department of Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China;3. Alashan Mongolian Hospital, Alxa Left Banner, Inner Mongolia 750306, China;1. Medicinal Chemistry Division, CSIR—Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India;2. Academy of Scientific & Innovative Research (AcSIR), CSIR—Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India;3. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab 160062, India;4. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab 160062, India |
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| Abstract: | An efficient procedure to prepare S-4-(3-thienyl)phenyl-α-methylacetic acid, an intermediate of a recently approved non-steroidal anti-inflammatory cyclooxygenase inhibitor atliprofen by enantioselective hydrolysis of the corresponding esters in presence of candida rugosa lipase is reported. The methyl and butyl esters of the racemic acid 2 were synthesized and subjected to enantioselective hydrolysis by the lipase to give S-4-(3-thienyl)phenyl-α-methylacetic acid upto 97.86% ee. The observed enantioselectivity during the hydrolysis of the substrate by the lipase was rationalized by molecular modeling studies. The methyl esters of both R and S-enantiomers of 4-(3-thienyl)phenyl-α-methylacetic acid, naproxen and ketoprofen were taken for the modeling studies. The results of the modeling studies are in conformity with the experimental observations. |
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