Keto esters chiral compound stereoselective synthesis

Chiral (3-hydroxy esters are versatile synthons in organic synthesis specifically in the preparation of natural products [68-70]. The asymmetrical reduction of carbonyl compounds using baker s yeast has been demonstrated and reviewed [5,71,72]. In the stereoselective reduction of P-keto ester of 4-chloro- and 4-bromo-3-oxobutanoic acid, specifically 4-chloro-3-oxobutanoic acid methyl ester, Sih and Chen [73] demonstrated that the stereoselectivity of yeast-catalyzed reductions may be altered by manipulating the size of ester group using y-chloroacetoacetate as substrate. They also indicated that the e.e. of the alcohol produced depended on the concentration of the substrate used. Nakamura et al. [74] demonstrated the reduction of p-keto ester with baker s yeast and controlled... 

So far, most microorganisms and enzymes derived therefrom have been used in the reduction of a single keto group of p-keto or a-keto compounds [68-71], Recently, Patel et al. [72] have demonstrated the stereoselective reduction of 3,5-dioxo-6-(benzyloxy)hexanoic acid, ethyl ester (41), to (3,S, 5R)-dihydroxy-6-(benzyloxy)hexanoic acid, ethyl ester (42a) (Fig. 14). The compound (42a) is a key chiral intermediate required for the chemical synthesis of [4-[4a,6P(E)]]-6-[4,4-bis(4-fluorophenyl)-3-(l-methyl-lH-tetrazol-5-yl)-l,3-butadienyl]-tetrahydro-4-hydroxy-2H-pyran-2-one, compound R-( + )-(43), a new anticholesterol drug that acts by inhibition of HMG CoA reductase [73], Among various microbial cultures evaluated for the stereoselective reduction of diketone (41), cell suspensions of Aci-... 

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