Gene mining, codon optimization and analysis of binding mechanism of an aldo-keto reductase with high activity, better substrate specificity and excellent solvent tolerance

The biosynthesis of chiral alcohols has important value and high attention. Aldo–keto reductases (AKRs) mediated reduction of prochiral carbonyl compounds is an interesting way of synthesizing single enantiomers of chiral alcohols due to the high enantio-, chemo- and regioselectivity of the enzymes. However, relatively little research has been done on characterization and apply of AKRs to asymmetric synthesis of chiral alcohols. In this study, the AKR from Candida tropicalis MYA-3404 (C. tropicalis MYA-3404), was mined and characterized. The AKR shown wider optimum temperature and pH. The AKR exhibited varying degrees of catalytic activity for different substrates, suggesting that the AKR can catalyze a variety of substrates. It is worth mentioning that the AKR could catalytic reduction of keto compounds with benzene rings, such as cetophenone and phenoxyacetone. The AKR exhibited activity on N,N-dimethyl-3-keto-3-(2-thienyl)-1-propanamine (DKTP), a key intermediate for biosynthesis of the antidepressant drug duloxetine. Besides, the AKR still has high activity whether in a reaction system containing 10%-30% V/V organic solvent. What’s more, the AKR showed the strongest stability in six common organic solvents, DMSO, acetonitrile, ethyl acetate, isopropanol, ethanol, and methanol. And, it retains more that 70% enzyme activity after 6 hours, suggesting that the AKR has strong solvent tolerance. Furthermore, the protein sequences of the AKR and its homology were compared, and a 3D model of the AKR docking with coenzyme NADPH were constructed. And the important catalytic and binding sites were identified to explore the binding mechanism of the enzyme and its coenzyme. These properties, predominant organic solvents resistance and extensive substrate spectrum, of the AKR making it has potential applications in the pharmaceutical field.

Recent Advance in Organocatalyzed Asymmetric Reduction of Prochiral Ketones: An Update

Chiral alcohols are important synthetic intermediates or building blocks for the diverse synthesis of drugs, agrochemicals, and natural products. Asymmetric reduction of prochiral ketones has been the most popularly investigated method for accessing chiral alcohols. In this regard, the organocatalyzed asymmetric reduction as a complementary of transition-metal- and enzyme-catalyzed reactions have attracted tremendous interest in the past decades due to the nature of metal-free and easy operation, as well as, principly, the ease of recovery and reuse of catalysts. Following up a comprehensive overview on organocatalyzed asymmetric reduction of prochiral ketones in early 2018, this short review is intended to summarize the recent progress in this area from the beginning of the year 2018 to the end of Aug. 2021.

Integrated Cobaloxime and Mesoporous Silica-Supported Ruthenium/Diamine Co-Catalysis for One-Pot Hydration/Reduction Enantioselective Sequential Reaction of Alkynes

This study developed a cost-efficient hydration/asymmetric transfer hydrogenation (ATH) process for the one-pot synthesis of valuable chiral alcohols from alkynes. During this process, the initial homogeneous cobaloxime-catalyzed hydration of alkynes was followed by heterogeneous Ru/diamine-catalyzed ATH transformation of the in-situ generated ketones, which provided varieties of chiral alcohols in good yields with up to 99% ee values. The immobilized Ru/diamine catalyst could be recycled at least three times before its deactivation in the sequential reaction system. This work shows a general method for developing one-pot asymmetric sequential catalysis towards sustainable organic synthesis.

Biocatalytic Silylation: The Condensation of Phenols and Alcohols with Triethylsilanol

Silicatein-α (Silα), a hydrolytic enzyme derived from siliceous marine sponges, is one of the few enzymes in nature capable of catalysing the metathesis of silicon–oxygen bonds. It is therefore of interest as a possible biocatalyst for the synthesis of organosiloxanes. To further investigate the substrate scope of this enzyme, a series of condensation reactions with a variety of phenols and aliphatic alcohols were carried out. In general, it was observed that Silα demonstrated a preference for phenols, though the conversions were relatively modest in most cases. In the two pairs of chiral alcohols that were investigated, it was found that the enzyme displayed a preference for the silylation of the S-enantiomers. Additionally, the enzyme’s tolerance to a range of solvents was tested. Silα had the highest level of substrate conversion in the nonpolar solvents n-octane and toluene, although the inclusion of up to 20% of 1,4-dioxane was tolerated. These results suggest that Silα is a potential candidate for directed evolution toward future application as a robust and selective biocatalyst for organosiloxane chemistry.

Asymmetric Synthesis of Organophosphorus Compounds using H-P reagents derived from Chiral Alcohols

Chiral organophosphorus compounds, especially those containing C-stereogenic carbons in the proximity of the phosphorus atom, are known for their unique properties and have found wide applications that span from medicinal...

Straightforward N-alkylation of diketopyrrolopyrroles through Mitsunobu reaction with benzyl, α-branched, and chiral alcohols

The N-alkylation of diketopyrrolopyrroles (DPPs) represents a fundamental step to ensure solubility and further processability. Commonly used nucleophilic subtitution on halogenated derivatives is replaced in this work by Mitsunobu reaction...

Iridium/f-Diaphos Catalyzed Asymmetric Hydrogenation of 2-Imidazolyl Aryl/Alkyl Ketones

The iridium/f-diaphos L5 or L12 catalyzed asymmetric hydrogenation of 2-imidazolyl aryl or alkyl ketones to afford two enantiomers of the desired chiral alcohols was firstly realized with high conversions (up...