Article
Chemistry, Physical
Shazia Iqbal, Maria A. Khan, Almas Jabeen, Sammer Yousuf, Fatima Zafar, Farhana Batool, Muhammad Uzair Ganatra, Fatima Z. Basha
Summary: （Summary:）
Reactive oxygen species (ROS) play an important role in oxidative stress-related diseases. Anti-inflammatory agents are crucial in controlling excessive ROS production. This study designed new harmine-linked triazole compounds as potential anti-inflammatory agents and evaluated their activity and cytotoxicity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Pharmacology & Pharmacy
Dezhi Kong, Yuan Tian, Kunfeng Duan, Wenyan Guo, Qingning Zhang, Panpan Zhang, Zuxiao Yang, Xia Qin, Leiming Ren, Wei Zhang
Summary: In this study, we identified 34 metabolites of doxazosin (DOX) in rats and analyzed their relationship based on kinetic parameters and multivariate statistical methods. The study revealed the stereoselective metabolic characteristics and mechanisms of DOX, and found significant differences in the metabolic profiles between the enantiomers. The results also demonstrated the importance of different in vivo and in vitro environments in influencing the metabolic characteristics of DOX. This study provides valuable insights into the pharmacokinetics and pharmacodynamics of DOX.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Organic
Ravi Varala, Hari Babu Bollikolla, Chandra Mohan Kurmarayuni
Summary: This review primarily focuses on the various synthetic strategies developed for 1,2,3-triazole scaffold and its derivatives up to June 2020, including metal-free, metal assisted, or bimetallic approaches. It also briefly discusses the applications and pharmacological activity of the important 1,2,3-triazole scaffold.
CURRENT ORGANIC SYNTHESIS
(2021)
Article
Chemistry, Organic
Ashish Kumar, Yamini, Pushkar Mehara, Poonam Sharma, Pralay Das
Summary: In this study, a semi-synthetic strategy was reported to synthesize a new class of compounds using a triazole moiety under Pd catalysis.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hina Siddiqui, M. A. A. Baheej, Saeed Ullah, Fazila Rizvi, Shazia Iqbal, Haroon M. Haniffa, Atia-tul Wahab, M. Iqbal Choudhary
Summary: A series of new 1,2,3-triazole derivatives were synthesized and evaluated for their inhibitory activity against alpha-glucosidase, with several compounds showing potent activity. Kinetics studies revealed different types of inhibition mechanisms for these compounds.
MOLECULAR DIVERSITY
(2022)
Article
Chemistry, Applied
Ming Li, Yunfeng Cui, Zefei Xu, Xi Chen, Jinhui Feng, Min Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: This study presents an enzymatic cascade reaction for the efficient synthesis of chiral intermediates with alpha,gamma-stereogenic centers, providing a new route for the synthesis of various bioactive compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Yunfeng Cui, Liangyan Zhu, Xi Chen, Jinhui Feng, Qiaqing Wu, Dunming Zhu
Summary: The study demonstrated a method for synthesizing the key precursor for ruxolitinib using PhADH to bioreduce 3-cyclopentyl-3-ketopropanenitrile. Rational engineering of the PhADH enzyme led to the double mutant H93C/A139L, which showed improved enantioselectivity and specific activity. This mutant enzyme was found to be effective in reducing beta-substituted-beta-ketonitriles at high concentrations.
Review
Chemistry, Multidisciplinary
Jinhui Feng, Qiaqing Wu, Dunming Zhu, Yanhe Ma
Summary: Steroids have been widely used in birth control, prevention, and treatment of various diseases, and they represent a major sector in the global pharmaceutical market. Advances in genetic and metabolic engineering have led to the production of steroidal precursors from phytosterols, replacing the use of sapogenins as starting materials. Synthetic biology holds promise in the design and construction of microbial cell factories for the industrial production of steroidal intermediates and APIs, leading to a greener steroidal pharmaceutical industry.
Article
Chemistry, Applied
Jianjiong Li, Shanshan Yu, Yingang Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: In this study, an omega-transaminase (ShdTA) from Sinirhodobacter hungdaonensis was identified and successfully used for the kinetic resolution of (S)-2-aminobutane, D-alanine, and D-homoalanine. This biocatalytic process offers a practical and efficient method for the synthesis of valuable small chiral amines and D-amino acids.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Applied
Zhuangzhuang Zhan, Zefei Xu, Shanshan Yu, Jinhui Feng, Fufeng Liu, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: In this study, an enzymatic dynamic kinetic resolution-asymmetric reductive amination was developed for the production of the key intermediate of tofacitinib. The method successfully synthesized cis-1-benzyl-N,4-dimethylpiperidin-3-amine with high stereoselectivity and diastereoselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Tingting Liu, Zefei Xu, Jinhui Feng, Shanshan Yu, Min Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: Two enantiocomplementary imine reductases (IREDs) with high enantioselectivity were identified through screening and engineering, which allowed the synthesis of a series of 1-heteroaryl tetrahydroisoquinolines with high to excellent ee values and isolated yields, providing an effective method for constructing pharmaceutically important alkaloids, including the intermediate of kinase inhibitor TAK-981.
Article
Chemistry, Physical
Tong Lv, Jinhui Feng, Xi Chen, Yuyang Luo, Qiaqing Wu, Dunming Zhu, Yanhe Ma
Summary: Mutant amine dehydrogenases (LsAmDHs) were developed through directed evolution from L-phenylalanine dehydrogenase, enabling the asymmetric reductive amination of 2,2-disubstituted-1,3-cyclopentadiones with high yield. This study not only synthesized the corresponding stereoisomeric fi-amino ketones, but also provided a useful tool for addressing the challenges in asymmetric reductive amination of diketones.
Article
Chemistry, Physical
Chuanhua Zhou, Xi Chen, Tong Lv, Xu Han, Jinhui Feng, Weidong Liu, Qiaqing Wu, Dunming Zhu
Summary: In this study, a unique halohydrin dehalogenase (AbHheG) was found to have high activity and alpha/beta-regioselectivity toward the ring opening of racemic styrene oxide with cyanate but with poor stereoselectivity. By reshaping the substrate-binding site of AbHheG, a variant Y15M/N182S was obtained with excellent alpha/beta-regioselectivity and stereoselectivity. This work demonstrated that halohydrin dehalogenase is a useful biocatalyst for the synthesis of both enantiomers of 4-aryl-2-oxazolidinones from readily available racemic styrene oxides.
Article
Chemistry, Organic
Liangyan Zhu, Xi Chen, Jinhui Feng, Yunfeng Cui, Qiaqing Wu, Dunming Zhu
Summary: A mutant L91C/F93I of the thermostable carbonyl reductase CBCR from Cupriavidus sp. BIS7 was obtained through semirational engineering. The mutant L91C/F93I showed 4- to 36-fold enhanced activities toward 2-methyl-2-benzyl-1,3-cyclopentanedione and its analogues, affording the (2R,3R)-stereoisomers with >99% ee and >99% de. Enzyme-substrate docking studies revealed the molecular basis for the activity and stereoselectivity improvements.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Hongliu Zhang, Xi Chen, Tong Lv, Qian Li, Weidong Liu, Jinhui Feng, Xiangtao Liu, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: In this study, a mutant M242F/Q245T of the carbonyl reductase from Sporobolomyces salmonicolor was found to enhance its activity toward both methyl 2-phthalimidomethyl-3-oxobutanoate(1a) and isopropanol, enabling the dynamic kinetic asymmetric reduction of 1a to a single stereoisomer of the product by hydrogen transfer from isopropanol. Structural and computational analysis suggested that the synergic effect of 242F and 245T reshaped the substrate entrance tunnel and enzyme active site. This study demonstrated that a carbonyl reductase can be engineered to improve its activity toward bulky ketones and isopropanol, and enable efficient preparation of the target chiral alcohol via substrate-coupled cofactor regeneration.
Article
Chemistry, Multidisciplinary
Yiyin Liu, Liangyan Zhu, Xuemei Li, Yunfeng Cui, Atefeh Roosta, Jinhui Feng, Xi Chen, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: In this study, a redox-neutral photocatalysis/enzymatic catalysis system was developed for the asymmetric synthesis of chiral 1,2-amino alcohols via decarboxylative radical C-C coupling. This strategy not only enables the efficient synthesis of a series of chiral amino alcohols in a green and sustainable manner but also has potential for the synthesis of bioactive molecules through novel C-C radical coupling transformations.
Article
Chemistry, Organic
Tingting Liu, Zefei Xu, Jinhui Feng, Shanshan Yu, Min Wang, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: Two highly enantioselective enantiocomplementary imine reductases (IREDs) were discovered through screening and enzyme engineering, which exhibited catalytic activity towards the reduction of 1-heteroaryl dihydroisoquinolines. By utilizing (R)-IR141-L172M/Y267F and (S)-IR40, a series of different 1-heteroaryl tetrahydroisoquinolines were efficiently synthesized with excellent enantioselectivity (82 to >99% ee) and high isolated yields (80 to 94%), providing an effective method for constructing pharmaceutically important alkaloids, including the intermediate of kinase inhibitor TAK-981.
Article
Chemistry, Multidisciplinary
Zefei Xu, Jinhui Feng, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: A general chemo-enzymatic approach for the efficient asymmetric synthesis of chiral 3-substituted tetrahydroquinolines has been developed, combining biocatalysis and the Buchwald-Hartwig cross-coupling reaction. The method involves a one-pot ene reductase (ERED)/imine reductase (IRED) cascade and successfully addresses the issue of racemization of the intermediate. This method offers a practical strategy for the construction of chiral 3-substituted tetrahydroquinolines.
Article
Chemistry, Physical
Yu Li, Peiyuan Yao, Shiqing Zhang, Jinhui Feng, Hao Su, Xiangtao Liu, Xiang Sheng, Qiaqing Wu, Dunming Zhu, Yanhe Ma
Summary: Selective activation and controllable transformation of formaldehyde is still a challenge, but researchers have engineered a benzaldehyde lyase to couple 3-hydroxypropanal and formaldehyde. They also identified a carbonyl reductase and a transaminase for the reduction or transamination of 1,4-dihydroxybutan-2-one. These enzymatic reactions were combined with chemocatalytic hydration of acrolein to synthesize optically pure 1,2,4-butanetriol and 2-aminobutane-1,4-diol. This study demonstrates a sustainable approach to the synthesis of high value-added chemicals from C1 molecules.
Article
Chemistry, Physical
Hongliu Zhang, Liangyan Zhu, Jinhui Feng, Xiangtao Liu, Xi Chen, Qiaqing Wu, Dunming Zhu
Summary: In this study, the alcohol dehydrogenase TbADH from Thermoanaerobacter brockii was improved through structure-guided directed evolution, resulting in enhanced enzyme activity and efficient catalysis of specific substrates, leading to the synthesis of complex molecules with multiple chiral centres.
CATALYSIS SCIENCE & TECHNOLOGY
(2022)
