title: Production of a pharmaceutical intermediate via biohydroxylation using whole cells of Rhodococcus rubropertinctus N82.
abstract: Rhodococcus rubropertinctus N82 possesses unique regiospecific hydroxylation activity in biotransformation of compounds. In this study, the ability of whole cells of the strain R. rubropertinctus N82 in biotransformation was studied. The hydroxylation activity resulted in transforming 6,7-dihydro-4H-thieno[3,2-c]-pyridine-5-carboxylic acid tert-butyl ester (LS1) into 2-hydroxy-6,7-dihydro-4H-thieno[3,2-c]-pyridine-5-carboxylic acid tert-butyl ester (LP1), a pharmaceutical intermediate. By optimizing conditions for the hydroxylating biotransformation using whole cells of R. rubropertinctus N82 as biocatalyst, 3.3 mM LP1 was successfully produced from 4 mM LS1 with a molar yield of 83%. Thus, effective method was newly developed to produce LP1, which is a synthetic intermediate of a platelet inhibitor active pharmaceutical ingredient drug, prasugrel.
authors.affiliation: a Industrial Microbiology , Graduate School of Agriculture, Kyoto University , Kyoto , Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Antonio
authors.initials: A
authors.lastname: Osorio-Lozada
authors.forename: Karen T
authors.initials: KT
authors.lastname: Robins
authors.forename: Makoto
authors.initials: M
authors.lastname: Hibi
authors.forename: Jun
authors.initials: J
authors.lastname: Ogawa
mesh_terms: D001711:Biotransformation; D046508:Culture Techniques; D006900:Hydroxylation; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012240:Rhodococcus / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations
keywords: Rhodococcus rubropertinctus; biotransformation; hydroxylation