Kinetic resolution of an indan derivative using Bacillus sp. SUI-12: synthesis of a key intermediate of the melatonin receptor agonist TAK-375.
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).
Tarui
Naoki
N
Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. Tarui_Naoki@takeda.co.jp
Nagano
Yoichi
Y
Sakane
Takeshi
T
Matsumoto
Kiyoharu
K
Kawada
Mitsuru
M
Uchikawa
Osamu
O
Ohkawa
Shigenori
S
Nakahama
Kazuo
K