Highly enantioselective bioreduction of ethyl 3-oxohexanoate

Ramos, Aline de Souza; Ribeiro, Joyce Benzaquem; Lopes, Raquel de Oliveira; Leite, Selma Gomes Ferreira; Souza, Rodrigo O. M. A. de

doi:10.1016/j.tetlet.2011.09.023

Cited by 12 publications

(11 citation statements)

References 30 publications

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“…Ethyl 3-oxohexanoate (ethyl butyrylacetate, CLXXIX) is reduced stereospecifically by a strain of A. niger to ethyl 3-(R)-hydroxyhexanoate (CLXXX), a food flavoring ingredient that also serves as a precursor for the synthesis of the chiral anticancer compound (+)-neopeltolide (Ramos et al 2011). …”

Section: Transformation Of Other Organic Compoundsmentioning

confidence: 99%

“…Unlike most of the steps in chemical syntheses, fungal biotransformations may be enantioselective. An example is the reduction of ethyl 3-oxohexanoate to the enantiomer ethyl 3-(R)-hydroxyhexanoate, with over 99 % enantiomeric excess, by a strain of A. niger (Ramos et al 2011). The chiral product can be used in the synthesis of phytotoxic compounds and anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

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Biotransformations of organic compounds mediated by cultures of Aspergillus niger

Parshikov

Woodling

Sutherland

2015

Appl Microbiol Biotechnol

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Many different organic compounds may be converted by microbial biotransformation to high-value products for the chemical and pharmaceutical industries. This review summarizes the use of strains of Aspergillus niger, a well-known filamentous fungus used in numerous biotechnological processes, for biochemical transformations of organic compounds. The substrates transformed include monocyclic, bicyclic, and polycyclic aromatic hydrocarbons; azaarenes, epoxides, chlorinated hydrocarbons, and other aliphatic and aromatic compounds. The types of reactions performed by A. niger, although not unique to this species, are extremely diverse. They include hydroxylation, oxidation of various functional groups, reduction of double bonds, demethylation, sulfation, epoxide hydrolysis, dechlorination, ring cleavage, and conjugation. Some of the products may be useful as new investigational drugs or chemical intermediates.

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Section: Transformation Of Other Organic Compoundsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biotransformations of organic compounds mediated by cultures of Aspergillus niger

Parshikov

Woodling

Sutherland

2015

Appl Microbiol Biotechnol

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“…It is noteworthy that among the synthetic method to obtain the hydroxyesters presented here, there are just few reports that use the Kluyveromyces genus (Ramos et al 2011, one of which used carbonyl reductase of K. thermotolerans ). The asymmetric bioreduction by whole cells of K. marxianus method was particularly effective in obtaining the (R)-hydroxyesters in high conversions and ee rate (Table I) The results demonstrated that yeast K. marxianus (Oliveira et al 2013, Molinari et al 1999, also easy to handle and growth like Saccharomyces cerevisiae, led to the (R)-hydroxyesters (1'b-4'b) without any other additive and in a greater extent than that reported for S. cerevisiae (Zeror et al 2010, Mahmoodi et al 2006.…”

Section: Bioconversion Of β-Ketoesters (1-6)mentioning

confidence: 99%

“…For example, the ethyl 3-hydroxybutanoate plays an important role in the synthesis of (+)-decarestrictine L, an inhibitor of cholesterol biosynthesis (Wang et al 2013), and the methyl 3-hydroxypentanoate is the key chiral building block in the synthesis of (-)-serricornine, the sex pheromone from cigarette SIMONE S.S. OLIVEIRA et al beetle, Lasioderma serricorne (Pilli and Riatto 1998). In the same way, ethyl 3-hydroxyhexanoate is an important intermediate for the synthesis of (+)-neopeltolide, a potent in vitro antiproliferative agent against the growth of several cancer cell lines and also antifungal activity against Candida albicans (Ramos et al 2011, Ghosh et al 2013. And also both enantiomeric forms of methyl 3-aryl-3-hydroxypropionates are important building blocks in the synthesis of several chiral drugs, fine chemicals and pesticides (Borowiecki andBretner 2013, Liu andLiu 2015).…”

Section: Introductionmentioning

confidence: 99%

Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess

Oliveira

Bello

Rodrigues

et al. 2017

An. Acad. Bras. Ciênc.

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This study presents the bioreduction of six β-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 β-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of β-stereogenichydroxyesters obtained by the same methodology. Four of these were obtained as (R)-configuration and two (S)-configuration, among them four compounds exhibited >99% enantiomeric excess. The β-ketoesters series LUMO maps showed that the β-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable β-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the β-ketoesters derivatives separating them into those provided predominantly (R)-or (S)-β-hydroxyesters. The HQSAR models for both (R)-and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of β-ketoesters scaffold as well as the substituents attached therein to asymmetric reduction, showing a possible influence of the ester group carbonyl position on the molecular conformation in the enzyme catalytic site, exposing a β-carbon side to the bioconversion to (S)-and (R)-enantiomers.

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“…This process can be facilitated by using either redox catalysts, in pure or semipure form, or biocatalysts [3]. The complex architecture of microorganisms and isolated enzymes made them as efficient catalysts for enantioselective conversions [4]. Unlimited availability of enzyme, internal cycling of co-factors and vigorous speed of catalysis made the whole-cell microorganisms as efficient catalysts for enantioselective resolution of racemic drugs as well as racemic intermediates.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Resolution of (R,S)-Carvedilol to (S)-(−)-Carvedilol by Biocatalysts

Swetha

Chandupatla

Veeresham

2017

Nat. Prod. Bioprospect.

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Among the microorganisms employed in the study, Aspergillus niger (GUFCC5443), Escherichia coli (ATCC9637), Streptomyces halstedii (CKM-2), Pseudomonas putida (NCIB9494), Cunninghamella elegans (NCIM689) and Sphingomonas paucimobilis (NCTC11030) were capable for the enantioselective conversion of racemic Carvedilol. Immobilization technique enhanced the enantioselectivity of microorganisms and thus increased the enantiomeric purity of the drug. Excellent enantiomeric ratios (E) were found in reactions catalyzed by immobilized A. niger and E. coli with values 174.44 and 104.26, respectively. Triacylglycerol lipase from Aspergillus niger was also employed in this study as a biocatalyst which resulted in the product with 83.35% enantiomeric excess (ee) and E of 11.34 while the enzyme on immobilization has yielded 99.08% ee and 216.39 E. The conversion yield (C%) of the drug by free-enzyme was 57.42%, which was enhanced by immobilization to 90.51%. Hence, our results suggest that immobilized triacylglycerol lipase from A. niger (Lipase AP6) could be an efficient biocatalyst for the enantioselective resolution of racemic Carvedilol to (S)-(−)-Carvedilol with high enantiomeric purity followed by immobilized cultures of A. niger and E. coli.

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Highly enantioselective bioreduction of ethyl 3-oxohexanoate

Cited by 12 publications

References 30 publications

Biotransformations of organic compounds mediated by cultures of Aspergillus niger

Biotransformations of organic compounds mediated by cultures of Aspergillus niger

Asymmetric bioreduction of β-ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess

Enantioselective Resolution of (R,S)-Carvedilol to (S)-(−)-Carvedilol by Biocatalysts

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