ORGANIC & BIOMOLECULAR CHEMISTRY
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2022
·Vol. 20
·期 14
·2909-2921
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IF 3.89
Haidi Yang,Jinyao Liu,Pan Hu,Liang Gao,Zedu Huang,Fener Chen
A new and highly stereoselective synthesis of chiral diol (S)-14, the common synthetic intermediate to (+)-(2R,4′R,8′R)-α-tocopherol (1), was accomplished in seven steps with 13.8% overall yield. This developed route featured a lipase-catalyzed desymmetric hydrolysis of prochiral diester 39a, which was prepared through a challenging Heck coupling, to chiral quaternary carbon-containing monoester (R)-37a of the correct configuration in 81% yield and 96.7% ee, to the best of our knowledge, leading to the most efficient enzymatic desymmetric synthesis of the chiral chroman skeleton of vitamin E members reported to date. Coupled with the modified preparation of the phytol-derived side chain, the chemoenzymatic total synthesis of 1 was completed in 15 longest linear steps with 3.1% overall yield.
研究领域:
有机化学
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合成化学
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酶学
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DOI
PubMed
高影响因子
Forensic Toxicology
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2018
·Vol. 37
·期 1
·121-131
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IF 3.924
Chen Lizhu,Yu Yingjia,Wang Yang,Xiang Ping,Duan Gengli
Purpose It is crucial for forensic analysis to differentiate clinical use from illegal abuse. Selegiline (SG) is mainly metabolized to desmethylselegiline (DM-SG), R -(−)-methamphetamine (R-MA) and R-(−)amphetamine (R-AM); while abused methamphetamine and amphetamine mainly contain the S -(+)-form. The aim of this study was to simultaneously determine SG, DM-SG, R / S -MA, and R / S -AM in human oral fluid (OF) and to differentiate clinical use from illegal use. We also aim to apply the present method to the OF samples from authentic cases in forensic toxicology. Methods Liquid–liquid extraction and liquid chromatography-tandem mass spectrometry operating in positive ion multiple-reaction monitoring mode were utilized. The chromatographic system consisted of a Chirobiotic TM V2 column (2.1 mm × 250 mm, 5 μm) and a mobile phase of methanol containing 0.1% (v/v) glacial acetic acid and 0.02% (v/v) ammonium hydroxide. Results and conclusions The calibration curves were linear from 1 to 100 ng/mL, and r > 0.995 for all analytes with imprecisions ≤ 15% and accuracy between 85 and 115%. Extraction recoveries ranged from 46.3 to 104.7% with coefficient of variation (CV) ≤ 10.3% and matrix effects (MEs) ranged from 47.4 to 114.8% with CV ≤ 12.9%. The lower limit of quantification was 0.2 ng/mL for SG and DM-SG and 1.0 ng/mL for S-MA, R-MA, S-AM and R-AM. The present method is simple, rapid (accomplished in 12 min), sensitive, and validated by authentic samples.
研究领域:
法医学
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分析化学
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产品关联
DOI
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
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2020
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IF 2.627
Haiyan Zhou,Yizuo Li,Rui Jiang,Xianlin Wang,Yuanshan Wang,Yaping Xue,Yuguo Zheng
R -2-(4-hydroxyphenoxy)propionic acid ( R -HPPA) is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed. The main route for R -HPPA biosynthesis is to hydroxylate the substrate R -2-phenoxypropionic acid ( R -PPA) at C-4 position with microbes. In order to provide sufficient R -PPA for the industrial production of R -HPPA, an effective R -PPA synthesis method was established and optimized in this work. The synthesis process mainly consisted of two steps: (1) synthesis of S -2-chloropropionic acid from L-alanine via diazotization and chlorination reactions; and (2) synthesis of R -PPA from S -2-chloropropionic acid and phenol via etherification reaction. The optimal reaction conditions were as follows: HCl: NaNO 2 : KI: L-Ala = 2.0: 1.2: 0.7: 1.0 (in molar), 125 °C reflux for 1.5 h, with KI as catalyst, and KI: S -2-chloropropionic acid: phenol = 0.075: 1.2: 1.0 (in molar). Under these conditions, an improved molar conversion rate (74.9%, calculated in phenol) was achieved. After extraction using anionic exchange resin Amberlite IRA-400 (CI), R -PPA product with a purity of 95.08% was obtained. The purified R -PPA was identified and evaluated in the application of the biotransformative production of R -HPPA. The results indicated that the synthesized R -PPA supported the R -HPPA biosynthesis with a comparable yield as that of the standard R -PPA. The R -PPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials, less toxicity of reagents, simple manipulations, and low equipment/instrument requirements.
研究领域:
生物化学
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有机化学
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工业微生物学
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产品关联
DOI
高影响因子
Drug Testing and Analysis
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2019
·Vol. 11
·期 6
·898-905
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IF 2.799
Lizhu Chen,Baohua Shen,Songtao Wang,Yingjia Yu,Hui Yan,Yan Shi,Gengli Duan,Ping Xiang
Background Chiral analysis is a crucial way to differentiate selegiline (SG) intake from drug abuse. Oral fluid (OF) has been successfully used as an alternative matrix for blood testing in several pharmacokinetic studies. Objective The aim of this study is to describe the pharmacokinetics of SG and its main metabolites in OF after a single oral administration of SG which is meaningful for results interpretation in forensic analysis. Methods Ten milligrams of SG were orally administered to 8 volunteers, and OF samples were collected for up to 96 hours by having participants spit into polypropylene tubes without stimulation. These samples were submitted to liquid–liquid extraction before analysis by liquid chromatography–tandem mass spectrometry operating in positive ion multiple-reaction monitoring mode. Results and conclusions After oral administration, each analyte could be detected in OF specimens from all volunteers with an initial detection time of 0.50 hours. The C max values of SG, R-MA, R-AM and DM-SG were 50.93–992.67 ng/mL, 29.78–653.64 ng/mL, 8.22–150.15 ng/mL, and 4.34–16.25 ng/mL, respectively, at 0.5 hours, 1–11 hours, 1.5–11 hours, and 0.5–6 hours post dose. The times when the compounds were last determined in OF were 5–24 hours for SG, 52–96 hours for R-MA, 31–96 hours for R-AM, and 13–31 hours for DM-SG after oral administration. There is a period of time in OF in which only MA and AM are present without SG and DM-SG after a single dose of SG. The pharmacokinetic data could provide supplementary interpretation for OF tests in forensic science and drug treatment programs.
研究领域:
法医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
·
IF 2.5
He Liu,Qian Gao,Kaiyue Zhang,Meng Xu,Hualei Wang,Dongzhi Wei
( R )-selective transaminases have the potential to act as efficient biocatalysts for the synthesis of important pharmaceutical intermediates. However, their low catalytic efficiency and unfavorable equilibrium limit their industrial application. Seven ( R )-selective transaminases were identified using homologous sequence mining. Beginning with the optimal candidate from Mycolicibacterium hippocampi , virtual mutagenesis and substrate tunnel engineering were performed to improve catalytic efficiency. The obtained variant, T282S/Q137E, exhibited 3.68-fold greater catalytic efficiency ( k cat / K m ) than the wild-type enzyme . Using substrate fed-batch and air sweeping processes, effective conversion of 100 mM 4-hydroxy-2-butanone was achieved with a conversion rate of 93 % and an ee value > 99.9 %. This study provides a basis for mutation of ( R )-selective transaminases and offers an efficient biocatalytic process for the asymmetric synthesis of ( R )-3-aminobutanol.
研究领域:
生物化学
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酶工程
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合成生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
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2013
·Vol. 28
·期 7
·994-1002
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IF 1.945
Ting Zhou,Ting Zhao,Qing Cheng,Shan Liu,Ling Xu,Wen Tan
A sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of R -bambuterol and its active metabolite R -terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R -bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C 18 column under gradient elution with a mobile phase consisting of methanol and water containing 5 m m ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R -bambuterol and R -terbutaline, respectively. The intra- and inter-day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high-throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R -bambuterol involving 10 healthy volunteers. Copyright © 2013 John Wiley & Sons, Ltd.
研究领域:
药理学
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分析化学
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临床医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
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2019
·
IF 3.782
Chen Lizhu,Yu Yingjia,Duan Gengli,Wang Xin,Shen Baohua,Xiang Ping
Objective: Chiral analysis is a crucial method to differentiate selegiline intake from drug abuse. A dried urine spot (DUS) analytical method based on spotting urine samples (10 μL) onto dried spot collection cards, and followed by air-drying and extraction, was developed and validated for the determination of selegiline, desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine.Methods: Methanol (0.5 mL) was found to be the ideal extraction solvent for target extraction from DUSs under orbital-horizontal stirring on a lateral shaker at 1,450 rpm for 30 min. Determinations were performed by direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) under positive electrospray ionization conditions using multiple reaction monitoring mode. The chromatographic system consisted of a ChirobioticTM V2 column (2.1 × 250 mm, 5 μm) and a mobile phase of methanol containing 0.1% (v/v) glacial acetic acid and 0.02% (v/v) ammonium hydroxide.Results and conclusions: The calibration curves were linear from 50 to 5,000 ng/mL, with r > 0.995 for all analytes, imprecisions ≤ 15% and accuracies between −11.4 and 11.7%. Extraction recoveries ranged from 48.6 to 105.4% with coefficients of variation (CV) ≤ 13.7%, and matrix effects ranged from 45.4 to 104.1% with CV ≤ 10.3%. The lower limit of quantification was 50 ng/mL for each analyte. The present method is simple, rapid (accomplished in 12 min), sensitive, and validated by a pharmacokinetic study in human urine collected after a single oral administration of SG.
研究领域:
分析化学
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药理学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
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2019
·
IF 3.163
Xiao-Ling Tang,Nan-Nan Zhang,Guo-Yan Ye,Yu-Guo Zheng
( R )-3-amino-1-butanol is a key intermediate of Dolutegravir for the treatment of HIV/AIDS and its green and efficient biosynthesis has attracted a great deal of attention. Transaminases are currently used as promising biocatalyst for the synthesis of chiral amines. However, many transaminases have ( S )-specificity and ( R )-selective transaminases were less exploited and studied, making the production of ( R )-amines remain challenging. In this study, a novel transaminase from Actinobacteria sp. ( As -TA) was obtained and applied for the biosynthesis of ( R )-3-amino-1-butanol by transferring the amino group from isopropylamine to 4-hydroxy-2-butanone. After optimization of the reaction condition and using a substrate fed-batch strategy, the conversion of 100, 200, 300, 400 and 500 mM 4-hydroxy-2-butanone reached 100%, 94.9%, 86.1%, 76.1% and 70.9%, respectively. ( R )-3-amino-1-butanol with a maximum yield of 29.6 g/L and 99.9% e.e. value was obtained. This was the first time demonstrating the successful biosynthesis of ( R )-3-amino-1-butanol with transaminase as biocatalyst and the obtained As -TA enriched the enzyme pool of transaminase with ( R )-specificity.
研究领域:
生物化学
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酶工程
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药物合成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
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2019
·Vol. 42
·期 10
·1573-1582
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IF 2.371
Zhou Hai-Yan,Li Yi-Zuo,Jiang Rui,Hu Hai-Feng,Wang Yuan-Shan,Liu Zhi-Qiang,Xue Ya-Ping,Zheng Yu-Guo
R -2-(4-hydroxyphenoxy)propionic acid ( R -HPPA) is a key intermediate of the enantiomerically pure phenoxypropionic acid herbicides. R -HPPA could be biosynthesized through selective introduction of a hydroxyl group (–OH) into the substrate R -2-phenoxypropionic acid ( R -PPA) at C-4 position, facilitated by microorganisms with hydroxylases. In this study, an efficient high-throughput screening method for improved R -HPPA biosynthesis through microbial hydroxylation was developed. As a hydroxylated aromatic product, R -HPPA could be oxidized by oxidant potassium dichromate to form brown-colored quinone-type compound. The concentration of R -HPPA can be quantified according to the absorbance of the colored compound at a suitable wavelength of 570 nm; and the R -HPPA biosynthetic capability of microorganism strains could also be rapidly evaluated. After optimization of the assay conditions, the high-throughput screening method was successfully used in identification of Beauveria bassiana mutants with enhanced R -HPPA biosynthesis capacity. A positive mutant C-7 with high tolerance to 20 g/L R -PPA was rapidly selected from 1920 mutants. The biomass and R -HPPA titer were 12.5- and 38.19-fold higher compared with the original strain at 20 g/L R -PPA. This high-throughput screening method developed in this work could also be a potential tool for screening strains producing other important phenolic compounds.
研究领域:
生物技术
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微生物学
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化学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
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2021
·
IF 6.707
Xin Li,Jingru Guan,Haopeng Jiang,Xianghai Song,Pengwei Huo,Huiqin Wang
Construction of multi-interface contact step-scheme (S-scheme) photocatalyst is a promising pathway to achieve high-electron transfer efficiency for photocatalytic CO 2 reduction. In this paper, g-C 3 N 4 nanosheets were selected as the main photocatalyst, rod-like CeO 2 (R-CeO 2 ) with unique Ce 4+ →Ce 3+ conversion property and rGO were loaded on the g-C 3 N 4 surface to construct 2D-1D-2D sandwich photocatalyst. The yields of CO and CH 4 were about 63.18 and 32.67 μmol/g after 4 h when the rGO/R-CeO 2 /g-C 3 N 4 was used as catalyst, which were about 4 and 6 times higher than that of pure CN, respectively. Cyclic experiments proved that the composite had excellent photocatalytic and material stability. Photoelectrochemical tests showed that the construction of S-scheme electron transfer model and the introduction of rGO can great enhance the electron transmission and separation of photogenerated electron-hole pairs. CO 2 adsorption test identified that the loading of R-CeO 2 and rGO obviously enhanced the CO 2 adsorption ability of pure g-C 3 N 4 . Density functional theory (DFT) calculations used to analyze the electron transfer path and the formation of the build-in electric field at the semiconductor interface. In-situ FTIR and 13 CO 2 element-tracer detection carried out to research the process of CO 2 photoreduction. A possible multi-interface contact S-scheme electron transfer mechanism for enhanced CO 2 photoreduction activity has been discussed.
研究领域:
材料科学
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环境科学
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产品关联
DOI
高影响因子
POLYMER ENGINEERING AND SCIENCE
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2024
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IF 3.2
Yanbo Li,Jinsuo Yu,Deyu Wei,Chengkai Liu,Yan Zhao,Junjia Bian,Shulin Sun,Hongwei Pan,Huili Yang,Lijing Han,Huiliang Zhang
Biodegradable materials provide protective properties comparable to conventional plastics while diminishing reliance on nonrenewable resources. Environmentally friendly polymer blends were prepared by melting poly(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) (PHBHHx) with poly (butylene succinate) (PBS). PBS was synthesized through esterification and polycondensation using 1,4-butanediol and succinic acid, with tetrabutyltitanate as the catalyst. The PHBHHx is supplied by Bulepha®PHA Company of China, model number BP330. The effects of PHBHHx content on thermal behavior, compatibility, and thermal stability of PBS/PHBHHx blends were systematically investigated. Differential scanning calorimetry (DSC) results indicated that the addition of PHBHHx influenced the crystallization behavior, the crystallization temperature ( T c ) of PBS decreased meanwhile, the crystallization half-time of PBS is reduced to 1.5 min compared with neat PBS (5 min) after isothermal is crystallized at 95°C. Polarized Optical Microscopy (POM) images also revealed that crystallization rate accelerated in the blend with increasing PHBHHx content. Rheological and Scanning Electron Microscopy (SEM) analysis demonstrated that incorporating a significant content of PHBHHx reduced compatibility between PBS and PHBHHx. Mechanical property testing indicates that the addition of PHBHHx reduced the toughness of blends. Additionally, the addition of a small amount of PHBHHx imparts a higher crystallinity (56%) and heat resistance of the PBS/PHBHHx blends (78°C) was higher than neat PBS (74°C). Highlights Laboratory synthesis of high molecular weight PBS. Optimal ratios improved crystallinity and thermal stability of blends. A systematic study of the crystallization properties of blends.
研究领域:
材料科学
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高分子科学
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Gege Ma,Xiangyu Zhu,Dongxin Zhang,Haoran Li,Jinping Lin,Dongzhi Wei
(R)-Citronellal is a key chiral precursor of high-value chemicals, such as the best-selling flavor compound (−)-menthol; however, the conventional synthesis suffers from low yield and unsatisfactory enantioselectivity. In this study, we developed a highly atom-efficient hydrogen-borrowing cascade for the synthesis of (R)-citronellal from geraniol using alcohol dehydrogenase from Escherichia coli K12 (AdhP) and ene-reductase from Saccharomyces cerevisiae YJM1341 (OYE2p). The key rate-limiting enzyme, AdhP, was subjected to structure-guided semirational engineering, and the triple mutant AdhP260T/284A/268P (M3) was obtained that demonstrated a 1.28-fold improvement in catalytic efficiency (kcat/Km) toward geraniol. After optimization of the reaction conditions, the hydrogen-borrowing cascade system achieved the conversion of 23.14 g/L geraniol into (R)-citronellal at a conversion rate of 98.23% with 96.7% ee. This work represents an alternative approach for the biosynthesis of (R)-citronellal without sacrificing a cosubstrate or additional enzymes.
研究领域:
生物化学
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合成生物学
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酶学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）