Asymmetric reductinon of carbonyl compounds by yeast. II. Preparation of optically active α- and β-hydroxy carboxylic acid derivatives

Abstract

α- and β-Keto esters and amides are readily reduced by an actively fermenting mutant of Saccharomyces cerevisiae and produce optically active α- and β-hydroxy esters and amides in moderate yields. Typically, methyl 2-oxo-2-phenylacetate gave methyl (R)-(-)-2-hydroxy- 2-phenyl- acetate; 2-oxo-2-phenylacetamide gave (R)-(-)-2-hydroxy-2- phenylacetamide; ethyl benzoylacetate gave ethyl (S)-(-)-3-hydroxy-3- phenylpropionate, and ethyl 2-oxocyclohexanecarboxylate gave ethyl (1R,2S)-(+)-2-hydroxycyclohexanecarboxylate. In each case, the product obtained was optically pure. However, the reduction of ethyl pyruvate to ethyl lactate produced partially racemized products.

Why Leave a Job Half Done? Recent Progress in Enzymatic Deracemizations

“…Hence, the bioreduction over the carbonyl moiety using an alcohol dehydrogenase is probably one of the most typical biocatalytic DKR systems, being described since 70's. [6] Recent examples include (Scheme 10a) the reduction of: i) α-substituted β-keto esters with commercial and overexpressed ADHs, [80,81] ii) α-substituted 1,3-diketones using commercial enzymes, [82] iii) α-substituted ketones employing overexpressed ADHs, [83] and iv) α-substituted aldehydes with an immobilized biocatalyst. [84] In all cases a pH close to neutral was enough to develop an efficient racemization of the labile position adjacent to the carbonyl reacting group.…”

“…Whereas the first non-enzymatic examples can be ascribed to enantioselective protonations, [5] in the case of enzymatic-mediated processes, the bioreduction of α-substituted ketones that can racemize under basic conditions are probably the first ones. [6] Among the different protocols to deracemize a racemic mixture (Scheme 1), dynamic kinetic resolutions, deracemizations via stereoinversion, cyclic deracemizations and enantioconvergent processes can be mentioned. This review, mainly covering the period from 2011 onwards, describes the application of these methods to the synthesis of enantioenriched compounds where the key step is performed by at least one biocatalyst.…”

Purification and characterization of two oxidoreductases involved in the enantioselective reduction of 3‐oxo, 4‐oxo and 5‐oxo esters in baker's yeast

“…The enantiomers of the hydroxy compounds formed were separated by gas chromatographic resolution of the diastereoisomeric derivatives obtained after derivatization with (R)-(+)-2-methoxy-2-trifluoromethylphenylacetic acid chloride and (R)-(+)-phenylethylisocyanate [14, 151, using a chemically bonded fused silica capillary column (DB 210, 30 m x 0.32 mm internal diameter). The elution order of the diastereoisomeric derivatives was determined by using reference compounds of known enantiomeric composition, obtained by yeast reduction [7,81.…”

“…Enantioselective reductions of carbonyl groups with baker's yeast are convenient methods to obtain optically pure hydroxy compounds and have previously been described for secondary alcohols [6] and different hydroxy acids and esters [7,81. Because of their bifunctional character, hydroxy acid esters are useful building blocks in organic chemistry and are employed as synthetic starting points for other chiral molecules [9].…”

Purification and Characterization of α-Keto Amide Reductase fromSaccharomyces cerevisiae

“…[7][8][9] For example, there are a few reports that the reduction of benzoylformamide, one of the aromatic -keto amides, with Saccharomyces cerevisiae gave to the corresponding (R)-hydroxy amide in 60-70% yield. 10,11) However, little information is known about the yeast reduction of other -keto amides and the properties of the related enzyme(s) in microbial cells.…”