Kinetic resolution of an indan derivative using Bacillus sp. SUI-12: Synthesis of a key intermediate of the melatonin receptor agonist TAK-375

• Published in: Journal of bioscience and bioengineering 2002, Vol.93 (1), p.44-47
• Main Authors: Tarui, Naoki, Nagano, Yoichi, Sakane, Takeshi, Matsumoto, Kiyoharu, Kawada, Mitsuru, Uchikawa, Osamu, Ohkawa, Shigenori, Nakahama, Kazuo
• Format: Article
• Language: English
• Subjects: AGONISTS; BACILLUS; Bacillus sp. SUI-12; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; chiral indan derivative; Fundamental and applied biological sciences. Psychology; kinetic resolution; MELATONIN; melatonin receptor agonist; Methods. Procedures. Technologies; scale-up
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/S1389-1723(02)80052-4

The chiral indan derivative ( S)-2 (2-[(8 S)-1,6,7,8-tetrahydro-2 H-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-2 H-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-[(8 S)-1,6,7,8-tetrahydro-2H-indeno[5,4- b]furan-8-yl]ethyl]propanamide).