Efficient Preparation of (R)-3-Hydroxypentanenitrile with High Enantiomeric Excess by Enzymatic Reduction with Subsequent Enhancement of the Optical Purity by Lipase-Catalyzed Ester Hydrolysis

2012 ◽  
Vol 76 (9) ◽  
pp. 1796-1798 ◽  
Author(s):  
Shigeru KAWANO ◽  
Junzo HASEGAWA ◽  
Yoshihiko YASOHARA
Keyword(s):  
Enantiomeric Excess ◽  
Optical Purity ◽  
Ester Hydrolysis ◽  
Enzymatic Reduction

scholarly journals Development of Quality Assessment Method for Optically Active Food Flavor Chemicals

2011 ◽  
Vol 94 (3) ◽  
pp. 923-930 ◽  
Author(s):  
Koichi Saito ◽  
Kouhei Hosono ◽  
Nariko Kitazawa ◽  
Yusuke Iwasaki ◽  
Rie Ito ◽  
...  
Keyword(s):  
Quality Assessment ◽  
Enantiomeric Excess ◽  
Optical Purity ◽  
Assessment Method ◽  
Optically Active ◽  
Standard Samples ◽  
Flavor Compound ◽  
Purity Test ◽  
Quality Assessment Method ◽  
Chemical Purity

Abstract A quality assessment method for commercially available, optically active flavor compounds, namely, menthol, menthyl acetate, borneol, perillaldehyde, and 1,8-cineol, was developed. A gas chromatograph equipped with a flame ionization detector and a DB-5ms capillary column was used for the chemical purity test. A GC/MS with a β-DEX cyclodextrin column was used for the optical purity test, by which the enantiomeric separation of each flavor compound was achieved. Enantiomeric excess was calculated as an expression of optical purity. Of the 25 standard samples subjected to the chemical purity test, six were found to have lower purity than the data provided by the manufacturers. When the same samples were subjected to the optical purity test, 11 were found to have lower purity than that indicated on the reagent labels. These results suggest that there is a need to conduct an optical purity test, in addition to a chemical purity test, for the quality assessment of flavor standards.

scholarly journals Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations

2019 ◽  
Vol 20 (5) ◽  
pp. 1188 ◽  
Author(s):  
Ye Liu ◽  
Youzhong Wan ◽  
Jingxuan Zhu ◽  
Muxin Li ◽  
Zhengfei Yu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Catalytic Reaction ◽  
Pyridoxal Phosphate ◽  
Binding Free Energy ◽  
Enantiomeric Excess ◽  
Optical Purity ◽  
Aromatic Amino Acids ◽  
Lysosomal Storage Diseases ◽  
Md Simulations ◽  
Lysosomal Storage

The aminotransferase from Bacillus circulans (BtrR), which is involved in the biosynthesis of butirosin, catalyzes the pyridoxal phosphate (PLP)-dependent transamination reaction to convert valienone to β-valienamine (a new β-glycosidase inhibitor for the treatment of lysosomal storage diseases) with an optical purity enantiomeric excess value. To explore the stereoselective mechanism of valienamine generated by BtrR, multiple molecular dynamics (MD) simulations were performed for the BtrR/PLP/valienamine and BtrR/PLP/β-valienamine complexes. The theoretical results showed that β-valienamine could make BtrR more stable and dense than valienamine. β-valienamine could increase the hydrogen bond probability and decrease the binding free energy between coenzyme PLP and BtrR by regulating the protein structure of BtrR, which was conducive to the catalytic reaction. β-valienamine maintained the formation of cation-p interactions between basic and aromatic amino acids in BtrR, thus enhancing its stability and catalytic activity. In addition, CAVER 3.0 analysis revealed that β-valienamine could make the tunnel of BtrR wider and straight, which was propitious to the removal of products from BtrR. Steered MD simulation results showed that valienamine interacted with more residues in the tunnel during dissociation compared with β-valienamine, resulting in the need for a stronger force to be acquired from BtrR. Taken together, BtrR was more inclined to catalyze the substrates to form β-valienamine, either from the point of view of the catalytic reaction or product removal.

scholarly journals Application of Lecitase® Ultra-Catalyzed Hydrolysis to the Kinetic Resolution of (E)-4-phenylbut-3-en-2-yl Esters

Catalysts ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 423 ◽  
Author(s):  
Aleksandra Leśniarek ◽  
Anna Chojnacka ◽  
Witold Gładkowski
Keyword(s):  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Optical Purity ◽  
Enantioselective Hydrolysis ◽  
Hydrolysis Of ◽  
Allyl Esters

The possibility of using Lecitase® Ultra as a novel alternative biocatalyst for the kinetic resolution of model racemic allyl esters of (E)-4-phenylbut-3-en-3-ol: Acetate (4a) and propionate (4b) through their enantioselective hydrolysis was investigated. Reaction afforded (+)-(R)-alcohol (3) and unreacted (−)-(S)-ester (4a or 4b). Hydrolysis of propionate 4b proceeded with higher enantioselectivity than acetate 4a. (R)-Alcohol (3) with highest enantiomeric excess (93–99%) was obtained at 20–30 °C by hydrolysis of propionate 4b, while the highest optical purity of unreacted substrate was observed for (S)-acetate 4a (ee = 34–56%). The highest enantioselectivity was found for the hydrolysis of propionate 4b catalyzed at 30 °C (E = 38). Reaction carried out at 40 °C significantly lowered enantiomeric excess of produced alcohol 3 and enantioselectivity in resolution. Lecitase® Ultra catalyzed the enantioselective hydrolysis of allyl esters 4a,b according to Kazlauskas’ rule to produce (R)-alcohol 3 and can find application as a novel biocatalyst in the processes of kinetic resolution of racemic allyl esters.

Enantioselective Preparation of Alcohols and Amines

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Medical Center ◽  
Phenylboronic Acid ◽  
Enantiomeric Excess ◽  
Direct Conversion ◽  
Single Step ◽  
Asymmetric Dihydroxylation ◽  
Enzymatic Reduction ◽  
Institute Of Technology ◽  
The University ◽  
Academy Of Sciences

Enzymatic reduction of a ketone can proceed in high enantiomeric excess, but this would require a stoichiometric amount of a reducing agent. Wolfgang Kroutil of the Karl-Franzens-Universität Graz devised (Angew. Chem. Int. Ed. 2008, 47, 741) a protocol for preparing the alcohol 2 in high ee starting from the racemic alcohol. The alcohol dehydrogenase chosen was selective for the R-alcohol, and the microorganism reduced the ketone so produced selectively to the S alcohol. James M. Takacs of the University of Nebraska established (J. Am. Chem. Soc. 2008, 130, 3734) that chiral Rh catalyzed addition of pinacolborane to a β,γ-unsaturated N-phenyl amide 3 proceeded with high enantiocontrol. The product organoborane was oxidized to the alcohol 4 . J. R. Falck of the UT Southwestern Medical Center used (J. Am. Chem. Soc. 2008, 130, 46) an organocatalyst to effect addition of phenylboronic acid to the γ-hydroxy enone 5, to give, after hydrolysis, the diol 6. John F. Hartwig of the University of Illinois effectively telescoped (Angew. Chem. Int. Ed. 2008, 47, 1928) alcohol formation and protection into a single step, by developing a procedure for the direct conversion of a primary allylic acetate 7 to the enantiomerically-enriched secondary benzyl ether 8. Tsutomu Katsuki of Kyushu University designed (Chemistry Lett. 2008, 37, 502) a catalyst for the enantioselective hydrocyanation of an aldehyde 9, by HCN transfer from the inexpensive 10. Mei-Xiang Wang of the Chinese Academy of Sciences, Beijing and Jieping Zhu of CNRS, Gif-sur-Yvette devised (Angew. Chem. Int. Ed. 2008, 47, 388) a catalyst for a complementary one-carbon homologation, the enantioselective Passerini three-component coupling of an aldehyde 12, an isonitrile 13, and an acid 14. Joseph M. Ready, also of UT Southwestern, developed (J. Am. Chem. Soc. 2008, 130, 7828) the preparation of enol benzoates such as 17 from the corresponding alkynes. Sharpless asymmetric dihydroxylation of 17 proceeded with high ee to give, after reduction, the diol 18. Toshiro Harada of the Kyoto Institute of Technology described (Angew. Chem. Int. Ed. 2008, 47, 1088) a potentially very practical enantioselective homologation, the catalyzed addition of an alkyl titanium, prepared in situ from the corresponding Grignard reagent, to the aldehyde 19, to give 21 in high ee.

Optical purity, enantiomeric excess and the Horeau effect

2020 ◽  
Vol 18 (35) ◽  
pp. 6801-6806
Author(s):  
Prasad L. Polavarapu
Keyword(s):  
Enantiomeric Excess ◽  
Optical Purity ◽  
Dimerization Constant

Optical purity (op) and enantiomeric excess (ee) become equal when either heterochiral dimerization constant is twice that of homochiral dimerization constant or specific rotations of monomer and dimer are equal.

scholarly journals Asymmetric Synthesis of Optically Pure Aliphatic Amines with an Engineered Robust ω-Transaminase

Catalysts ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1310
Author(s):  
Linhan Dong ◽  
Qinglong Meng ◽  
Carlos Ramírez-Palacios ◽  
Hein J. Wijma ◽  
Siewert J. Marrink ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Enantiomeric Excess ◽  
Optical Purity ◽  
Structural Features ◽  
Thermostable Enzyme ◽  
Aliphatic Amines ◽  
Vibrio Fluvialis ◽  
Catalytic Potential ◽  
Improved Performance ◽  
Optically Pure

The production of chiral amines by transaminase-catalyzed amination of ketones is an important application of biocatalysis in synthetic chemistry. It requires transaminases that show high enantioselectivity in asymmetric conversion of the ketone precursors. A robust derivative of ω-transaminase from Pseudomonasjessenii (PjTA-R6) that naturally acts on aliphatic substrates was constructed previously by our group. Here, we explore the catalytic potential of this thermostable enzyme for the synthesis of optically pure aliphatic amines and compare it to the well-studied transaminases from Vibrio fluvialis (VfTA) and Chromobacterium violaceum (CvTA). The product yields indicated improved performance of PjTA-R6 over the other transaminases, and in most cases, the optical purity of the produced amine was above 99% enantiomeric excess (e.e.). Structural analysis revealed that the substrate binding poses were influenced and restricted by the switching arginine and that this accounted for differences in substrate specificities. Rosetta docking calculations with external aldimine structures showed a correlation between docking scores and synthetic yields. The results show that PjTA-R6 is a promising biocatalyst for the asymmetric synthesis of aliphatic amines with a product spectrum that can be explained by its structural features.

scholarly journals Synthesis and analysis of 4-(3-fluoropropyl)-glutamic acid stereoisomers to determine the stereochemical purity of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) for clinical use

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243831
Author(s):  
Kai-Ting Shih ◽  
Ya-Yao Huang ◽  
Chia-Ying Yang ◽  
Mei-Fang Cheng ◽  
Yu-Wen Tien ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Glutamic Acid ◽  
Scale Up ◽  
Enantiomeric Excess ◽  
Optical Purity ◽  
Daily Basis ◽  
Brain Diseases ◽  
Ductal Adenocarcinoma ◽  
Chiral Hplc ◽  
Clinical Use

(4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is a positron emission tomography (PET) imaging agent for measuring the system xC− transporter activity. It has been used for the detection of various cancers and metastasis in clinical trials. [18F]FSPG is also a promising diagnostic tool for evaluation of multiple sclerosis, drug resistance in chemotherapy, inflammatory brain diseases, and infectious lesions. Due to the very short half-life (110 min) of 18F nuclide, [18F]FSPG needs to be produced on a daily basis; therefore, fast and efficient synthesis and analytical methods for quality control must be established to assure the quality and safety of [18F]FSPG for clinical use. To manufacture cGMP-compliant [18F]FSPG, all four nonradioactive stereoisomers of FSPG were prepared as reference standards for analysis. (2S,4S)-1 and (2R,4R)-1 were synthesized starting from protected L- and D-glutamate derivatives in three steps, whereas (2S,4R)-1 and (2R,4S)-1 were prepared in three steps from protected (S)- and (R)-pyroglutamates. A chiral HPLC method for simultaneous determination of four FSPG stereoisomers was developed by using a 3-cm Chirex 3126 column and a MeCN/CuSO4(aq) mobile phase. In this method, (2R,4S)-1, (2S,4S)-1, (2R,4R)-1, and (2S,4R)-1 were eluted in sequence with sufficient resolution in less than 25 min without derivatization. Scale-up synthesis of intermediates for the production of [18F]FSPG in high optical purity was achieved via stereo-selective synthesis or resolution by recrystallization. The enantiomeric excess of intermediates was determined by HPLC using a Chiralcel OD column and monitored at 220 nm. The nonradioactive precursor with >98% ee can be readily distributed to other facilities for the production of [18F]FSPG. Based on the above accomplishments, cGMP-compliant [18F]FSPG met the acceptance criteria in specifications and was successfully manufactured for human use. It has been routinely prepared and used in several pancreatic ductal adenocarcinoma metastasis-related clinical trials.

scholarly journals Synthesis, Enantiomeric Resolution and Biological Evaluation of HIV Capsid Inhibition Activity for Racemic, (S)- and (R)-PF74

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3919
Author(s):  
Stuart Ruddell ◽  
Elena Sugrue ◽  
Sarah Memarzadeh ◽  
Lorna Mae Hellam ◽  
Sam J. Wilson ◽  
...  
Keyword(s):  
Biological Activities ◽  
Enantiomeric Excess ◽  
Optical Purity ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Chiral Hplc ◽  
Enantiomeric Resolution ◽  
Hiv Replication ◽  
Computational Docking ◽  
Lack Of Information

PF74 is a capsid-targeting inhibitor of HIV replication that effectively perturbs the highly sensitive viral uncoating process. A lack of information regarding the optical purity (enantiomeric excess) of the single stereogenic centre of PF74 has resulted in ambiguity as to the potency of different samples of this compound. Herein is described the synthesis of enantiomerically enriched (S)- and (R)-PF74 and further enrichment of the samples (≥98%) using chiral HPLC resolution. The biological activities of each enantiomer were then evaluated, which determined (S)-PF74 (IC50 1.5 µM) to be significantly more active than (R)-PF74 (IC50 19 µM). Computational docking studies were then conducted to rationalise this large discrepancy in activity, which indicated different binding conformations for each enantiomer. The binding energy of the conformation adopted by the more active (S)-PF74 (ΔG = −73.8 kcal/mol) was calculated to be more favourable than the conformation adopted by the less active (R)-enantiomer (ΔG = −55.8 kcal/mol) in agreement with experimental observations.

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