title: Stereoselective epoxidation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile.
abstract: The chiral intermediate (3S,4R)-trans-3,4-dihydro-3,4-dihydroxy-2,2-dimethyl- 2H-1-benzopyran-6-carbonitrile [(+)-trans diol 3] was made by the stereoselective microbial epoxidation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 1. This compound is a potential intermediate for the total synthesis of potassium-channel openers. Several microbial cultures were found which catalyzed the transformation of 1 to the corresponding (3S,4S)-epoxide 2 and (+)-trans diol 3. The two best cultures, Corynebacterium sp. SC 13876 and Mortierella ramanniana SC 13840 gave reaction yields of 32 M% and 67.5 M% and optical purities of 88 and 96%, respectively, for (+)-trans diol 3. A single-stage process (fermentation-epoxidation) for the biotransformation of 1 was developed using Corynebacterium sp. SC 13876 and M. ramanniana SC 13840. In a 25-L fermentor, the (+)-trans diol 3 was obtained in 38.6 M% yield with an optical purity of 90% using Corynebacterium SC 13876. The reaction yield of 60.7 M% and optical purity of 92.5% were obtained for (+)-trans diol 3 using M. ramanniana SC 13840. A two-stage process for the preparation of (+)-trans diol 3 was also developed using a 3 L cell-suspension (10% w/v, wet cells) of M. ramanniana SC 13840. The reaction was carried out in a 5-L Bioflo fermentor. The concentration of substrate 1 was 2 g L-1 with glucose present at 10 g L-1. After 48 h, (+)-trans diol 3 was obtained in 76 M% yield with an optical purity of 96%.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Microbial Technology, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903.
authors.forename: R N
authors.initials: RN
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: B
authors.initials: B
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Howell
authors.forename: C
authors.initials: C
authors.lastname: McNamee
authors.forename: D
authors.initials: D
authors.lastname: Brzozowaski
authors.forename: J
authors.initials: J
authors.lastname: North
authors.forename: D
authors.initials: D
authors.lastname: Kronenthal
authors.forename: L
authors.initials: L
authors.lastname: Szarka
mesh_terms: D001419:Bacteria / Q000254:growth & development / Q000378:metabolism*; D001578:Benzopyrans / Q000737:chemistry*; D003352:Corynebacterium / Q000378:metabolism; D004852:Epoxy Compounds; D005285:Fermentation; D005658:Fungi / Q000254:growth & development / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009090:Mucorales / Q000378:metabolism; D009570:Nitriles / Q000737:chemistry*; D009615:Nocardia / Q000378:metabolism; D010843:Pichia / Q000378:metabolism; D011549:Pseudomonas / Q000378:metabolism; D012240:Rhodococcus / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: C091069:2,2-dimethyl-2H-1-benzopyran-6-carbonitrile; D001578:Benzopyrans; D004852:Epoxy Compounds; D009570:Nitriles