Asymmetric direduction of 1,2-indanedione to cis (1S,2R) indanediol by Trichosporon cutaneum MY 1506

Cis (1S,2R) indanediol is a potential precursor to (-)-cis (IS,2R)-1-aminoi ndan-2-ol, a key chiral synthon for a leading HIV protease inhibitor, Crixi van(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 bi ocatalyst. 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 yiel d of 99.1% and an enantiomeric excess of >99%. When scaled up in a 23-l bio reactor, 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 scal e-up also yielded 0.9 g of the more polar trans (1S,2S) indanediol diastere omer, a minor bioreduction product. Supercritical fluid chromatography anal yses 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.