AI Article Synopsis
- Cis (1S,2R) indanediol is a crucial precursor in creating (-)-cis (1S,2R)-1-aminoindan-2-ol, which is essential for the HIV protease inhibitor Crixivan.
- A study identified the yeast strain Trichosporon cutaneum MY 1506 as an effective biocatalyst for converting 1,2-indanedione into cis (1S,2R) indanediol, achieving an impressive yield of 99.1% and over 99% enantiomeric excess in initial tests.
- When the process was scaled up to a 23-liter bioreactor, the strain produced 8.4 grams of pure
Article 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.
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