88271-13-0

Upstream product

• 64-17-5 ethanol 
• 3347-90-8 (2S)-2-hydroxybutanoic acid 
• 15933-07-0 Ethyl 2-oxobutanoate 
• 533-68-6 2-bromobutyric acid ethyl ester 
• 88241-56-9 ethyl (2S)-2-acetoxybutanoate 

Downstream Products

• 112597-15-6 (S)-3-[(2,2-Dimethyl-1-methylene-propoxy)-methyl-phenyl-silanyloxy]-butyric acid ethyl ester 

Relevant academic research and scientific papers

Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin

t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.

Dynamic kinetic resolution of α-substituted β-ketoesters catalyzed by Baeyer-Villiger monooxygenases: Access to enantiopure α-hydroxy esters

BVMOs make a play: The dynamic kinetic resolution of racemic α-alkyl-β-ketoesters was performed through a selective Baeyer-Villiger oxidation employing different Baeyer-Villiger monooxygenases (BVMOs) in mild basic media. The product diesters were obtained with excellent yields and enantioselectivities, and used as precursors for optically active α-hydroxy esters.

Enantioselectivity of haloalkane dehalogenases and its modulation by surface loop engineering

In the loop: Engineering of the surface loop in haloalkane dehalogenases affects their enantiodiscrimination behavior. The temperature dependence of the enantioselectivity (lnE versus 1/T) of β-bromoalkanes by haloalkane dehalogenases is reversed (red data points) by deletion of the surface loop; the selectivity switches back when an additional single-point mutation is made. This behavior is not observed for -bromoesters.

Systematic investigation of Saccharomyces cerevisiae enzymes catalyzing carbonyl reductions

Eighteen key reductases from baker's yeast (Saccharomyces cerevisiae) have been overproduced in Escherichia coli as glutathione S-transferase fusion proteins. A representative set of α- and β-keto esters was tested as substrates (11 total) for each purified fusion protein. The stereoselectivities of β-keto ester reductions depended both on the identity of the enzyme and the substrate structure, and some reductases yielded both L- and D-alcohols with high stereoselectivities. While α-keto esters were generally reduced with lower enantioselectivities, it was possible in all but one case to identify pairs of yeast reductases that delivered both alcohol antipodes in optically pure form. Taken together, the results demonstrate not only that individual yeast reductases can be used to supply important chiral building blocks, but that GST-fusion proteins allow rapid identification of synthetically useful biocatalysts (along with their corresponding genes).

Purification and characterization of two alpha-keto ester reductases from Streptomyces thermocyaneoviolaceus IFO 14271.

Two NADPH-dependent alpha-keto ester reductases (Streptomyces thermocyaneoviolaceus keto ester reductase, STKER-II and -III) were purified from S. thermocyaneoviolaceus IFO 14271, one of thermophilic actinomycetes. The molecular masses of native STKER-II

Stereocontrolled reduction of α- and β-keto esters with micro green algae, Chlorella strains

The stereocontrolled reduction of α- and β-keto esters using micro green algae was accomplished by a combination of the cultivation method and the introduction of an additive. The reduction of ethyl pyruvate and ethyl benzoylformate by the photoautotrophically cultivated Chlorella sorokiniana gave the corresponding alcohol in high e.e. (>99% e.e. (S) and >99% e.e. (R), respectively). In the presence of glucose as an additive, the reduction of ethyl 3-methyl-2-oxobutanoate by the heterotrophically cultivated C. sorokiniana afforded the corresponding (R)-alcohol. On the other hand, the reduction in the presence of ethyl propionate gave the (S)-alcohol. Ethyl 2-methyl-3-oxobutanoate was reduced in the presence of glycerol by the photoautotrophically cultivated C. sorokiniana or the heterotrophically cultivated C. sorokiniana to the corresponding syn-(2R,3S)-hydroxy ester with high diastereo- and enantiomeric excess (e.e.). Some additives altered the stereochemical course in the reduction of α- and β-keto esters.

Bidentate chelation-controlled asymmetric synthesis of α-hydroxy esters based on the glycolate enolate alkylation

(S)-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl](4-methoxyphenyl)methanol (4b) has been synthesized and evaluated as a chiral auxiliary for the asymmetric synthesis of α-hydroxy esters based on bidentate chelation-controlled alkylation of glycolate enolate. (C) 2000 Elsevier Science Ltd.

Asymmetric reduction of α-keto esters and α-diketones with a bakers' yeast keto ester reductase

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.

Mechanistic study for stereochemical control of microbial reduction of α-keto esters in an organic solvent

To elucidate the mechanism for stereochemical control of yeast reduction of α-keto esters in organic media, seven enzymes responsible for the reduction have been isolated from bakers' yeast and kinetic parameters for enzymatic reductions have been measured. In yeast reduction of ethyl 3-methyl-2-oxobutanoate (1f), enantiomeric excess in the produced (R)-hydroxy ester increases when an organic solvent is used as the reaction medium in place of water. Difference in K(m) of the enzymes contributes largely to the stereochemistry of reduction by whole yeast cell. Four enzymes contribute to catalytic reduction of 1f. K(m) of the (R)-producing enzyme has been found to be the lowest among those of four enzymes. Stereochemical course of the reduction shifts toward the (R)-product by lowering the substrate concentrations, because the (R)-producing enzyme is most active among the enzymes under diluted conditions. In yeast reduction of ethyl 2-oxohexanoate (1d), the corresponding (S)-hydroxy ester is obtained in water, whereas the antipode is given in benzene. Five enzymes participate to the reduction of 1d and the (R)-producing enzymes have smaller K(m)s than those of the (S)-producing enzymes. When the reaction is run in benzene, however, the produced α-hydroxy ester does not undergo further decomposition. The inhibition of enzymatic decomposition in an organic solvent is also accounted for by low concentration of α-hydroxy ester in aqueous phase surrounding the bakers' yeast.

Reductive Biotransformation of Carbonyl Compounds --- Application of Fungus Geotrichum sp. G38 in Organic Synthesis

The microbial transformation of 2- and 3-oxo esters and diketones with Geotrichum sp.G38 and its application to the syntheses of the key intermediates of several bioactive compounds such as (R)-denopamine 8, (R)-fluoxetine 11 and (2S,3R)-sitophilate 14 were described.