Asymmetric synthesis of lipitor chiral intermediate using a robust carbonyl reductase at high substrate to catalyst ratio

Xu, Guochao; Tang, Minghui; Ni, Ye

doi:10.1016/j.molcatb.2015.11.001

Cited by 20 publications

(13 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ST-10 (PAR) have been constructed through directed evolution, fully converting 200 g/L ethyl 4-chloro-3-oxobutanoate into ethyl ( S )-4-chloro-3-hydroxybutyrate in the presence of 15% ( v / v ) 2-propanol [14,15]. Furthermore, attempts with biphasic catalysis in the presence of water-immiscible organic solvents have demonstrated an intriguing potential for overcoming the inhibition from substrate/co-substrate, increasing the solubility of substrates, easy product removal, decreasing the spontaneous hydrolysis of substrate/product, and avoiding unfavorable equilibria [16,17,18,19]. In an aqueous/octanol biphasic system, the biosynthesis process of ethyl ( R )-4-chloro-3-hydroxybutyrate using a stereoselective carbonyl reductase from Burkholderia gladioli was established, in which 1.2 M ethyl 4-chloro-3-oxobutanoate was completely converted to afford ethyl ( R )-4-chloro-3-hydroxybutyrate through the substrate fed-batch strategy [20].…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine

et al. 2018

View full text Add to dashboard Cite

The recombinant carbonyl reductase from Rhodococcus erythropolis WZ010 (ReCR) demonstrated strict (S)-stereoselectivity and catalyzed the irreversible reduction of N-Boc-3-piperidone (NBPO) to (S)-N-Boc-3-hydroxypiperidine [(S)-NBHP], a key chiral intermediate in the synthesis of ibrutinib. The NAD(H)-specific enzyme was active within broad ranges of pH and temperature and had remarkable activity in the presence of higher concentration of organic solvents. The amino acid residue at position 54 was critical for the activity and the substitution of Tyr54 to Phe significantly enhanced the catalytic efficiency of ReCR. The kcat/Km values of ReCR Y54F for NBPO, (R/S)-2-octanol, and 2-propanol were 49.17 s−1 mM−1, 56.56 s−1 mM−1, and 20.69 s−1 mM−1, respectively. In addition, the (S)-NBHP yield was as high as 95.92% when whole cells of E. coli overexpressing ReCR variant Y54F catalyzed the asymmetric reduction of 1.5 M NBPO for 12 h in the aqueous/(R/S)-2-octanol biphasic system, demonstrating the great potential of ReCR variant Y54F for practical applications.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Enzymatic synthesis of enantiopure products is highly regarded because of high enantio-/regio-/chemo-selectivity, rapid conversion, and moderate conditions. − The poor acidic/basic/metal/solvent stability of natural enzymes precludes scale-up applications; however, the unique mechanism of the catalytic sites can be adopted in the design of other efficient catalysts. − In essence, substrate molecules are immobilized by the confinement of enzyme pockets via multiple binding interactions, such as hydrogen bonding, π–π interactions, and electrostatic effects. These stereochemically defined objects are then attacked by an active group from a certain orientation to realize the highly selective conversion. , …”

Section: Introductionmentioning

confidence: 99%

Enzyme-Inspired Assembly: Incorporating Multivariate Interactions to Optimize the Host–Guest Configuration for High-Speed Enantioselective Catalysis

Deng

Meng

et al. 2020

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

To achieve a rapid asymmetry conversion, the substrate objects suffer from accelerated kinetic velocity and random rotation at the cost of selectivity. Inspired by natural enzymes, optimizing the host–guest configuration will realize the high-performance enantioselective conversion of chemical reactions. Herein, multivariate binding interactions were introduced into the 1D channel of a chiral catalyst to simulate the enzymatic action. An imidazolium group was used to electrophilically activate the CO unit of a ketone substrate, and the counterion binds the hydrogen donor isopropanol. This binding effect around the catalytic center produces strong stereo-induction, resulting in high conversion (99.5% yield) and enantioselectivity (99.5% ee) for the asymmetric hydrogenation of biomass-derived acetophenone. In addition, the turnover frequency of the resulting catalyst (5160 h–1 TOF) is more than 58 times that of a homogeneous Ru-TsDPEN catalyst (88 h–1 TOF) under the same condition, which corresponds to the best performance reported till date among all existing catalysts for the considered reaction.

show abstract

“…Atorvastatin possesses the character of excellent therapeutic effect and lower side effect, which is the inhibitor of hydroxylmethylglutaryl CoA reductase . Recently, asymmetric biocatalytic reduction of ethyl 4‐chloro‐3‐oxobutanoate (COBE) to corresponding chiral alcohol CHBE by whole cells has received considerable attention owing to the regeneration of cofactors in situ and higher stereoselectivity under environmentally friendly reaction conditions . Some studies have been reported on the microbial reduction of COBE to ( S )‐CHBE .…”

Section: Introductionmentioning

confidence: 99%

“…3,4 Recently, asymmetric biocatalytic reduction of ethyl 4-chloro-3-oxobutanoate (COBE) to corresponding chiral alcohol CHBE by whole cells has received considerable attention owing to the regeneration of cofactors in situ and higher stereoselectivity under environmentally friendly reaction conditions. [5][6][7][8] Some studies have been reported on the microbial reduction of COBE to (S)-CHBE. [9][10][11][12] However, the product yield is not satisfactory at higher concentrations of COBE in aqueous buffer media.…”

Section: Introductionmentioning

confidence: 99%

New ionic liquid increase the catalytic efficiency of recombinant Escherichia coli cells‐mediated asymmetric reduction

Fan

Zhang

et al. 2018

J of Chemical Tech & Biotech

View full text Add to dashboard Cite

Background Ionic liquids (ILs) have advantages in terms of flexible structure and composition for the whole cell mediated biocatalytic reaction. However, the lack of design strategy for ILs has hampered the development of biocatalysis in non‐aqueous medium. In the present study, to establish an efficient reaction system to obtain vital chiral compounds, a novel IL was designed by combining the superior characteristics of quaternary ammonium‐ and dialkyl‐based cationic surfactant IL to enhance the recombinant Escherichia coli cells‐catalyzed bioreduction efficiency. Results [HOEtN1,1,1][BF4] was synthesized and showed excellent characteristics of low toxicity to the biocatalyst, reduced toxicity of substrate to the microbial cells and moderate increase of cell membrane permeability. In the [HOEtN1,1,1][BF4]‐ containing reaction system, some valuable factors involved in the biocatalytic reduction of ethyl 4‐chloro‐3‐oxobutanoate to ethyl (S)‐4‐chloro‐3‐hydroxybutanoate were found to be: 2.5% (w/v) [HOEtN1,1,1][BF4], 20% (v/v) isopropanol, 3 M COBE, pH 7.0, 30 °C, reacted for 16 h. A yield of 96.7% was obtained under the optimum conditions with above 99% enantiomeric excess value, and the proposed bioprocess was also successfully scaled up to a 5 L fermentor with a yield of 90.7%. Conclusion The developed IL [HOEtN1,1,1][BF4] is a promising solvent for enhancing the efficiency of model bioreduction. It was also evaluated for broadening its application to the biosynthesis of (R)‐[3,5‐bis(trifluoromethyl)phenyl] ethanol catalyzed by recombinant Escherichia coli, with remarkable success. © 2018 Society of Chemical Industry

show abstract

Asymmetric synthesis of lipitor chiral intermediate using a robust carbonyl reductase at high substrate to catalyst ratio

Cited by 20 publications

References 34 publications

Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine

Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine

Enzyme-Inspired Assembly: Incorporating Multivariate Interactions to Optimize the Host–Guest Configuration for High-Speed Enantioselective Catalysis

New ionic liquid increase the catalytic efficiency of recombinant Escherichia coli cells‐mediated asymmetric reduction

Contact Info

Product

Resources

About