Asymmetric Direduction of 1, 2-Indanedione to cis (1S, 2R) Indanediol by Trichosporon cutaneum MY 1506

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Cis (1S, 2R) indanediol is a potential precursor to (-)-cis (1S, 2R)-1-aminoindan-2-ol, a key chiral synthon for a leading HIV protease inhibitor, Crixivan^(○!R) (Indinavir). A potential route to the biosynthesis of this important precursor, the microbial asymmetric direduction of 1, 2-indanedione to its corresponding diol, cis (1S, 2R) indanediol, was investigated. The screening of 32 yeast strains yielded Trichosporon cutaneum MY 1506 as a suitable biocatalyst. At the 2-l shake-flask scale, 1, 2-indanedione (charged at 1.0 g/l) was bioconverted to cis (1S, 2R) indanediol at a final bioconversion yield of 99.1% and an enantiomeric excess of >99%.When scaled up in a 23-l bioreactor, T.cutaneum produced 8.4 g of pure cis (1S, 2R) indanediol, and the isolated yield of cis (1S, 2R) indanediol was 52%. Purification of the scale-up also yielded 0.9 g of the more polar trans (1S, 2S) indanediol diastereomer, a minor bioreduction product. Supercritical fluid chromatography analyses of the purified cis (1S, 2R) and trans (1S, 2S) indanediol demonstrated that the enantiomeric excesses during this bioconversion scale-up were 99% and 26%, respectively.
公益社団法人日本生物工学会の論文
1999-11-25