Kinetic Resolution of an Indan Derivative Using Bacillus sp.SUI-12 : Synthesis of a Key Intermediate of the Melatonin Receptor Agonist TAK-375

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The chiral indan derivative (S)-2 (2-|(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b|furan-8-yl] ethylamine) 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).
社団法人日本生物工学会の論文
2002-01-25