Stereoselective Enzymatic Reduction of 1,4-Diaryl-1,4-Diones to the Corresponding Diols Employing Alcohol Dehydrogenases

Mourelle‐Insua, Ángela; Gonzalo, Gonzalo de; Lavandera, Iván; Gotor‐Fernández, Vicente

doi:10.3390/catal8040150

Cited by 9 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preparation of chiral 1,4-diaryl-1,4-diols from sterically hindered 1,4-diaryl-1,4-diketones has been accomplished using the ADH from Ralstonia sp. [17]; in this case, diols were the main products with no significant accumulation of the intermediate hydroxyketones. Enzymatic reduction of 2,2-disubstituted 1,3alkanediones (with different substitution patterns on the tetrahedral carbon C2) is remarkably attractive from a synthetic point of view, since the biocatalyst may accomplish enantioselective hydrogen transfer with simultaneous stereo-discrimination between the two groups bond to the tetrahedral center C2, thus giving one stereoisomer as major final product.…”

Section: Introductionmentioning

confidence: 75%

Stereoselective Reduction of Prochiral Cyclic 1,3-Diketones Using Different Biocatalysts

et al. 2019

View full text Add to dashboard Cite

We have developed biocatalytic methods for the stereoselective reduction of cyclic prochiral 1,3diketones for the production of optically active β-hydroxyketones and/or 1,3-diols. The recombinant ketoreductase KRED1-Pglu (formulated as purified catalyst) and whole cells of wild type E. coli DE3 Star were used as biocatalysts, displaying different and sometimes complementary stereoselectivity, thus allowing the preparation of stereochemically pure β-hydroxyketones (12-66% isolated yields, >99% e.e.) and 1,3-diols (40-60% isolated yields, > 99% e.e.).

show abstract

Section: Introductionmentioning

confidence: 75%

Stereoselective Reduction of Prochiral Cyclic 1,3-Diketones Using Different Biocatalysts

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Next, the bioreductions of telluro‐acetophenones 3a–g were investigated (Table ) under previously established conditions . As biocatalysts, lyophilized cells of Escherichia coli ( E. coli ) overexpressing ADH from Ralstonia species (Ras‐ADH), Lactobacillus brevis (Lb‐ADH), Sphingobium yanoikuyae (Sy‐ADH), Thermoanaerobacter ethanolicus (Tes‐ADH), Thermoanaerobacter species (ADH‐T), Rhodococcus ruber (ADH‐A) and the commercially available evo 1.1.200 were assayed.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Bioreduction of Telluro‐Acetophenones to Optically Active Hydroxy Tellurides

2020

Self Cite

View full text Add to dashboard Cite

Organotellurium compounds exhibit a broad range of useful applications in organic synthesis, materials science and medicinal chemistry fields. Despite their increasing applicability, the synthesis of enantiomerically pure organotellurium compounds remains nowadays scarcely reported in the literature. Herein, the chemical synthesis and biocatalyzed reductions of a set of telluro‐acetophenones using both (R) and (S)‐selective alcohol dehydrogenases (ADHs) is described for the first time, obtaining enantiomerically enriched hydroxy tellurides with excellent selectivities under very mild reaction conditions. On the one hand, enantiopure para‐substituted (S)‐hydroxy tellurides were obtained using the Ras‐ADH (77–95 % conversion) and ADH‐A (52–75 %), the ADH‐A leading to the enantiopure (S)‐hydroxy tellurides substituted at the meta‐position (69–75 %). On the other hand, the evo‐1.1.200 displayed high selectivity towards the preparation of optically alcohols with substitutions at the para‐position of the aromatic ring (60–68 % conversion and 92–97 % ee), while the Lb‐ADH led to the best results when reducing bulky ketones at the meta‐position (79–82% conversion and 88–99 % ee).

show abstract

“…(Scheme 4). 46 This was the first example of chiral 1,4diaryl-1,4-diol production by ADH, which thereby demonstrated a remarkable capacity for ADHs to recognize and accommodate bulky substrates. Presumably, more valuable diaryl KREDs and ADHs could be obtained by genome mining with an RasADH probe.…”

Section: Sources and Propertiesmentioning

confidence: 92%

Stereochemistry in Asymmetric Reduction of Bulky–Bulky Ketones by Alcohol Dehydrogenases

Zhou

2020

ACS Catal.

View full text Add to dashboard Cite

Biocatalyzed asymmetric reduction of ketones is one of the most cost-effective and environmentally friendly approaches for preparing chiral alcohols. However, few natural ketone reductases (KREDs) or alcohol dehydrogenase (ADHs) with high activity and stereoselectivity toward bulky–bulky ketones have yet been reported due to the strong steric hindrance of these substrates. Recent developments in protein engineering have led to biocatalysts capable of producing chiral alcohols with high efficiency and stereoselectivity. This review discusses recent advances in several approaches for the manipulation of stereoselectivity, including engineering of the binding pocket and active site loops to accommodate bulky–bulky ketones, modulating the electronic effects on attraction and repulsion between binding pocket residues and substituents of ketone substrates, and adding traceless directing groups to substrates to alter their orientation. Microbial sources of KREDs and ADHs, screening techniques, and future outlooks for the field are also discussed.

show abstract

Stereoselective Enzymatic Reduction of 1,4-Diaryl-1,4-Diones to the Corresponding Diols Employing Alcohol Dehydrogenases

Cited by 9 publications

References 51 publications

Stereoselective Reduction of Prochiral Cyclic 1,3-Diketones Using Different Biocatalysts

Stereoselective Reduction of Prochiral Cyclic 1,3-Diketones Using Different Biocatalysts

Stereoselective Bioreduction of Telluro‐Acetophenones to Optically Active Hydroxy Tellurides

Stereochemistry in Asymmetric Reduction of Bulky–Bulky Ketones by Alcohol Dehydrogenases

Contact Info

Product

Resources

About