title: Kinetic resolution of an indan derivative using Bacillus sp. SUI-12: synthesis of a key intermediate of the melatonin receptor agonist TAK-375.
abstract: The chiral indan derivative (S)-2 (2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl-amine) was synthesized by enzyme-catalyzed asymmetric hydrolysis of the racemic acetamide 1 (N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl]acetamide). The reaction was carried out using Bacillus sp. SUI-12 screened for the ability to hydrolyze 1 to give (S)-2 with high enantioselectivity. In a scaled-up experiment, a low reaction rate was observed. However, by changing the culture medium and the reaction conditions, it became possible to run the reaction to 40% conversion on a 10-g or more scale, obtaining (S)-2 at >;99% enantiomeric excess (ee). The (S)-2 obtained was available for the synthesis of the melatonin receptor agonist TAK-375 (N-[2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl]propanamide).
authors.affiliation: Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. Tarui_Naoki@takeda.co.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Tarui
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nagano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakane
authors.forename: Kiyoharu
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawada
authors.forename: Osamu
authors.initials: O
authors.lastname: Uchikawa
authors.forename: Shigenori
authors.initials: S
authors.lastname: Ohkawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakahama