Methyl -4-bromo-3-hydroxybutyrate

To this end, several routes passing through the known (S)-methyl-4-bromo-3-hydroxybutyrate 26, an intermediate used m prior syntheses of HMGRIs, were developed. This key intermediate was derived most efficiently from isoascorbic acid as shown in Scheme 5. Protection of 26 as the f-butyl-dimethylsilylether, followed by conversion to the nitnle provided an advanced intermediate (27) that could be taken in several directions. 

Scheme 5. Synthesis of (S)-methyl-4-bromo-3-hydroxybutyrate derivatives.

Asako et al. found a novel reductase in P. citrinum IF04631 18,52], which could reduce methyl 4-bromo-3-oxobutyrate (BAM) to methyl (S)-4-bromo-3-hydroxybu-tyrate (BHBM), a usefiil pharmaceutical intermediate for the synthesis of HMG-CoA reductase inhibitors as wdl as (S)-4chiral intermediate is much higher than CHBE because of the existence of bromine atom however, BHBM is quite toxic for biocatalysts. Therefore, the enzyme catalyzing the reduction of BAM should possess tolerance toward such compounds. 

Asako, H., Shimizu, M Makino, Y and Itoh, N. (2010) Biocatalytic reduction system for the production of chiral methyl (R)/(S)-4-bromo-3-hydroxybutyrate. Tetrahedron Lett.. 51, 2664—2666. 

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