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

2002; Elsevier BV; Volume: 93; Issue: 1 Linguagem: Inglês

10.1016/s1389-1723(02)80052-4

1389-1723

Naoki Tarui, Yoichi Nagano, Takeshi Sakane, Kiyoharu Matsumoto, Mitsuru Kawada, Osamu Uchikawa, Shigenori Ohkawa, Kazuo Nakahama,

Chemical Reaction Mechanisms

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).