Asymmetric Reduction of α-Keto Esters and α-Diketones with a Bakers’ Yeast Keto Ester Reductase

Abstract

Optically pure α-hydroxy esters and α-hydroxy ketones have been synthesized by the reduction of the corresponding ketones with a keto ester reductase isolated from bakers’ yeast (YKER-I). The reduction of α-keto esters affords the corresponding (S)- or (R)-hydroxy esters selectively, where the stereochemical course depends on the chain length of the alkyl substituent on the carbonyl group. An α-keto short alkanoic ester affords the corresponding (S)-hydroxy ester, whereas a long alkanoate yields the corresponding (R)-hydroxy ester. The reduction of α-diketones affords the corresponding (S)-2-hydroxy ketones regio- and stereoselectively.

Promiscuous Substrate Binding Explains the Enzymatic Stereo‐ and Regiocontrolled Synthesis of Enantiopure Hydroxy Ketones and Diols

“…The bioreduction of diketones has not been extensively studied, [19][20][21][22][23][24][25][26] and in several cases microorganisms or plants [27][28][29][30][31][32] were used for this purpose. Thus, the obtained results in terms of regioand stereoselectivity usually remained unclear.…”

“…[9][10][11][12][13][14][15][16][17][18] In the particular case of the synthesis of enantiopure hydroxy ketones and/or diols starting from the corresponding diketones employing isolated ADHs, there are few examples available in the literature. [19][20][21][22][23][24][25][26] In other cases plants or microorganisms are employed, [27][28][29][30][31][32] frequently affording a mixture of stereo-and regioisomers due to the action of several enzymes with different and/or opposite selectivities. These derivatives are important building blocks of many natural compounds, [33,34] such as pheromones [35,36] or antitumor agents like discodermolide.…”

New and Convenient Chemoenzymatic Syntheses of (S)-2-Hydroxy-3-octanone, the Major Pheromone Component of Xylotrechus spp., and Its R-Enantiomer

“…14 Chiral nonenzymatic synthesis of (S)-1 and eventually (R)-1 has been accomplished by Sharpless asymmetric epoxidation of (±)-1-octen-3-ol, 15 a coupling reaction of L-lactic acid and D-alanine, respectively, with amyllithium, 12 and treatment of (S)-ethyl lactate with 1-bromopentane. 14 Enzymatic synthesis of these compounds has only been performed by reduction of the 1,2-diketone precursor either with a keto ester reductase isolated from baker's yeast, 16 with a diacetyl reductase from Bacillus stearothermophilus and the system glucose 6-phosphate/glucose 6-phosphate dehydrogenase, 10 or with baker's yeast in the presence of an enzyme inhibitor. 11 Important drawbacks of these reductions are the overreduction to the corresponding diols, and the lack of regioselectivity providing two regioisomeric acyloins.…”

One-pot synthesis of α-hydroxy ketones from captodative formyl(amino)alkenes

“…2 These methods were succesfully applied to the synthesis of optically pure α-ketols. [3][4][5][6][7] However, the search for new methods of the construction of an α-hydroxy carbonyl moiety is of considerable current interest because this fragment is a common structural unit of many biologically active derivatives. [8][9][10][11] This communication deals with the chemistry of easily available captodative formyl(amino)alkenes 1 for the synthesis of α-hydroxy ketones.…”