title: Asymmetric direduction of 1,2-indanedione to cis (1S,2R) indanediol by Trichosporon cutaneum MY 1506.
abstract: 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 (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,2R) 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.
authors.affiliation: Department of Bioprocess R&D, Merck Research Laboratories, RY80Y-105, Rahway, NJ 07065, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stahl
authors.forename: N
authors.initials: N
authors.lastname: Ikemoto
authors.forename: A
authors.initials: A
authors.lastname: King
authors.forename: R
authors.initials: R
authors.lastname: Greasham
authors.forename: M
authors.initials: M
authors.lastname: Chartrain