scholarly journals Flavin-Dependent Halogenases Catalyze Enantioselective Olefin Halocyclization

2020 ◽  
Author(s):  
Dibyendu Mondal ◽  
Brian F. Fisher ◽  
Yuhua Jiang ◽  
Jared C. Lewis
Keyword(s):  
Organic Chemistry ◽  
Catalytic Activity ◽  
High Selectivity ◽  
Organic Transformations ◽  
Docking Simulations ◽  
Bond Forming ◽  
Reaction Optimization ◽  
Wide Range ◽  
Site Selective ◽  
Insight Into

<div><div><div><p>Catalytic enantioselective halocyclization of alkenes is a powerful bond forming tool in synthetic organic chemistry and a key step in the biosynthesis of several natural products. To date, however, no examples of enantioselective halocyclization of simple achiral olefins catalyzed by enzymes have been reported. Herein, we report that flavin-dependent halogenases (FDHs) previously engineered to catalyze site-selective aromatic halogenation can also catalyze bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Analysis of the selectivity of FDH variants along the lineage for the most selective enzymes reveals mutations responsible for the emergence of halocyclase activity, and docking simulations provide insight into the origins of improvements imparted by these mutations. High selectivity was achieved by characterizing and mitigating the release of HOBr from FDH variants using a combination of protein engineering and reaction optimization. Given the range of different halocyclization reactions and other organic transformations that proceed via oxidative halogenation, this expansion of FDH catalytic activity bodes well for the development of a wide range of biocatalytic halogenation reactions.</p></div></div></div>

scholarly journals Flavin-Dependent Halogenases Catalyze Enantioselective Olefin Halocyclization

2020 ◽  
Author(s):  
Dibyendu Mondal ◽  
Brian F. Fisher ◽  
Yuhua Jiang ◽  
Jared C. Lewis
Keyword(s):  
Organic Chemistry ◽  
Catalytic Activity ◽  
High Selectivity ◽  
Organic Transformations ◽  
Docking Simulations ◽  
Bond Forming ◽  
Reaction Optimization ◽  
Wide Range ◽  
Site Selective ◽  
Insight Into

<div><div><div><p>Catalytic enantioselective halocyclization of alkenes is a powerful bond forming tool in synthetic organic chemistry and a key step in the biosynthesis of several natural products. To date, however, no examples of enantioselective halocyclization of simple achiral olefins catalyzed by enzymes have been reported. Herein, we report that flavin-dependent halogenases (FDHs) previously engineered to catalyze site-selective aromatic halogenation can also catalyze bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Analysis of the selectivity of FDH variants along the lineage for the most selective enzymes reveals mutations responsible for the emergence of halocyclase activity, and docking simulations provide insight into the origins of improvements imparted by these mutations. High selectivity was achieved by characterizing and mitigating the release of HOBr from FDH variants using a combination of protein engineering and reaction optimization. Given the range of different halocyclization reactions and other organic transformations that proceed via oxidative halogenation, this expansion of FDH catalytic activity bodes well for the development of a wide range of biocatalytic halogenation reactions.</p></div></div></div>

scholarly journals Flavin-dependent halogenases catalyze enantioselective olefin halocyclization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dibyendu Mondal ◽  
Brian F. Fisher ◽  
Yuhua Jiang ◽  
Jared C. Lewis
Keyword(s):  
Organic Chemistry ◽  
Catalytic Activity ◽  
Protein Engineering ◽  
Natural Product ◽  
Active Site ◽  
Natural Product Biosynthesis ◽  
Bond Forming ◽  
Reaction Optimization ◽  
Wide Range ◽  
Site Selective

AbstractHalocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclization of simple olefins would therefore have significant synthetic value. Flavin-dependent halogenases (FDHs) catalyze halogenation of arene and enol(ate) substrates. Herein, we reveal that FDHs engineered to catalyze site-selective aromatic halogenation also catalyze non-native bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Highly selective halocyclization is achieved by characterizing and mitigating the release of HOBr from the FDH active site using a combination of reaction optimization and protein engineering. The structural origins of improvements imparted by mutations responsible for the emergence of halocyclase activity are discussed. This expansion of FDH catalytic activity presages the development of a wide range of biocatalytic halogenation reactions.

scholarly journals Modern Synthetic Methods for the Stereoselective Construction of 1,3-Dienes

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 249
Author(s):  
Raquel G. Soengas ◽  
Humberto Rodríguez-Solla
Keyword(s):  
Organic Chemistry ◽  
Natural Products ◽  
Functional Group ◽  
Biological Activities ◽  
Synthetic Methods ◽  
Bond Forming ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

The 1,3-butadiene motif is widely found in many natural products and drug candidates with relevant biological activities. Moreover, dienes are important targets for synthetic chemists, due to their ability to give access to a wide range of functional group transformations, including a broad range of C-C bond-forming processes. Therefore, the stereoselective preparation of dienes have attracted much attention over the past decades, and the search for new synthetic protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged in the last decade, with a focus on the synthetic processes that meet the requirements of efficiency and sustainability of modern organic chemistry.

The controllable synthesis of substitutional and interstitial nitrogen-doped manganese dioxide: the effects of doping sites on enhancing the catalytic activity

2020 ◽  
Vol 8 (17) ◽  
pp. 8383-8396 ◽  
Author(s):  
Taohong He ◽  
Xiaoshan Zeng ◽  
Shaopeng Rong
Keyword(s):  
Catalytic Activity ◽  
Manganese Dioxide ◽  
Deep Insight ◽  
Controllable Synthesis ◽  
Nitrogen Doped ◽  
N Doping ◽  
Interstitial Nitrogen ◽  
A Site ◽  
Site Selective ◽  
Insight Into

N atoms were selectively doped at substitutional or interstitial sites in the MnO2 lattice using N2 plasma. This research provides a site-selective N-doping method and a deep insight into the different effects of doping sites.

Ultrasound-Promoted Organic Synthesis – A Recent Update

2021 ◽  
Vol 25 ◽  
Author(s):  
Goutam Brahmachari ◽  
Nayana Nayek ◽  
Mullicka Mandal ◽  
Anindita Bhowmick ◽  
Indrajit Karmakar
Keyword(s):  
Organic Chemistry ◽  
Green Chemistry ◽  
Organic Synthesis ◽  
Ultrasound Irradiation ◽  
Present Review ◽  
Organic Transformations ◽  
Reaction Conditions ◽  
Catalytic Systems ◽  
Bond Forming ◽  
Reducing Energy

: Ultrasonication, nowadays, is well-regarded as an effective green tool in implementing a plethora of organic transformations. The last decade has seen quite useful applications of ultrasound irradiation in synthetic organic chemistry. Ultrasound has already come out as a unique technique in green chemistry practice, for its inherent properties of minimizing wastes and reducing energy and time, thereby increasing the product yields with higher purities under milder reaction conditions. The present review summarizes ultrasound-promoted useful organic transformations involving both carbon-carbon and carbon-heteroatom (N, O, S) bond-forming reactions in the absence or presence of varying catalytic systems, reported during the period 2016-2020.

scholarly journals Inhibition of human carboxylesterases by ginsenosides: structure–activity relationships and inhibitory mechanism

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhao-Hui Sun ◽  
Jing Chen ◽  
Yun-Qing Song ◽  
Tong-Yi Dou ◽  
Li-Wei Zou ◽  
...  
Keyword(s):  
High Selectivity ◽  
Hydroxyl Groups ◽  
Inhibitory Effects ◽  
Docking Simulations ◽  
Structure Activity ◽  
Potent Inhibition ◽  
Wide Range ◽  
Competitive Inhibitors ◽  
First Time ◽  
Hydrolysis Of

Abstract Background Human carboxylesterases (hCES) are key serine hydrolases responsible for the hydrolysis of a wide range of endogenous and xenobiotic esters. Although it has been reported that some ginsenosides can modulate the activities of various enzymes, the inhibitory effects of ginsenosides on hCES have not been well-investigated. Methods In this study, more than 20 ginsenosides were collected and their inhibitory effects on hCES1A and hCES2A were assayed using the highly specific fluorescent probe substrates for each isoenzyme. Molecular docking simulations were also performed to investigate the interactions between ginsenosides and hCES. Results Among all tested ginsenosides, Dammarenediol II (DM) and 20S-O-β-(d-glucosyl)-dammarenediol II (DMG) displayed potent inhibition against both hCES1A and hCES2A, while protopanaxadiol (PPD) and protopanaxatriol (PPT) exhibited strong inhibition on hCES2A and high selectivity over hCES1A. Introduction of O-glycosyl groups at the core skeleton decreased hCES inhibition activity, while the hydroxyl groups at different sites might also effect hCES inhibition. Inhibition kinetic analyses demonstrated that DM and DMG functioned as competitive inhibitors against hCES1A-mediated d-luciferin methyl ester (DME) hydrolysis. In contrast, DM, DMG, PPD and PPT inhibit hCES2A-mediated fluorescein diacetate (FD) hydrolysis via a mixed manner. Conclusion The structure–inhibition relationships of ginsenosides as hCES inhibitors was investigated for the first time. Our results revealed that DM and DMG were potent inhibitors against both hCES1A and hCES2A, while PPD and PPT were selective and strong inhibitors against hCES2A.

Ionic Liquid Assisted C-C Bond Formation

2020 ◽  
Vol 24 (16) ◽  
pp. 1853-1875
Author(s):  
Mandeep Kaur ◽  
Opinder Kaur ◽  
Rahul Badru ◽  
Sandeep Kaushal ◽  
Pritpal Singh
Keyword(s):  
Ionic Liquids ◽  
Heterogeneous Catalysts ◽  
Bond Formation ◽  
Solvent System ◽  
Solid Support ◽  
Organic Transformations ◽  
Diverse Range ◽  
Bond Forming ◽  
The Past ◽  
Wide Range

With their ability to dissolve inorganic as well as organic materials, ionic liquids have emerged as a versatile solvent system for a diverse range of organic transformations. In the past few decades, the literature has witnessed remarkable advances in a wide range of organic conversions carried out in the presence of various imidazolium, pyridinium, pyrrolidinium, quinolinium and diazobicyclo-octane based ionic liquids. In the reaction, ionic liquids serve as a solvent, catalyst or sometimes both. In certain cases, they are also modified with metal nanoparticles or complexes to form heterogeneous catalysts or are immobilized onto solid support like agar-agar to act as solid-support catalysts. Reactions catalysed by ionic liquids incorporating chiral catalysts possess the advantageous features of being highly enantioselective and reproducible, besides being economical and easy to handle. In this review, an updated insight regarding the role played by ionic liquids in various C-C bond-forming organic reactions, has been summarized.

Advances in Carbon–Element Bond Construction under Chan–Lam Cross-Coupling Conditions: A Second Decade

Synthesis ◽  
2020 ◽  
Author(s):  
Ajesh Vijayan ◽  
Desaboini Nageswara Rao ◽  
K. V. Radhakrishnan ◽  
Patrick Y. S. Lam ◽  
Parthasarathi Das
Keyword(s):  
Bond Formation ◽  
Nitrogen Heterocycles ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Labeled Compounds ◽  
Bond Forming ◽  
Carbon Nucleophiles ◽  
Coupling Conditions ◽  
Reaction Optimization ◽  
Wide Range

AbstractCopper-mediated carbon–heteroatom bond-forming reactions involving a wide range of substrates have been in the spotlight for many organic chemists. This review highlights developments between 2010 and 2019 in both stoichiometric and catalytic copper-mediated reactions, and also examples of nickel-mediated reactions, under modified Chan–Lam cross-coupling conditions using various nucleophiles; examples include chemo- and regioselective N-arylations or O-arylations. The utilization of various nucleophiles as coupling partners together with reaction optimization (including the choice of copper source, ligands, base, and other additives), limitations, scope, and mechanisms are examined; these have benefitted the development of efficient and milder methods. The synthesis of medicinally valuable or pharmaceutically important nitrogen heterocycles, including isotope-labeled compounds, is also included. Chan–Lam coupling reaction can now form twelve different C–element bonds, making it one of the most diverse and mild reactions known in organic chemistry.1 Introduction2 Construction of C–N and C–O Bonds2.1 C–N Bond Formation2.1.1 Original Discovery via Stoichiometric Copper-Mediated C–N Bond Formation2.1.2 Copper-Catalyzed C–N Bond Formation2.1.3 Coupling with Azides, Sulfoximines, and Sulfonediimines as Nitrogen­ Nucleophiles2.1.4 Coupling with N,N-Dialkylhydroxylamines2.1.5 Enolate Coupling with sp3-Carbon Nucleophiles2.1.6 Nickel-Catalyzed Chan–Lam Coupling2.1.7 Coupling with Amino Acids2.1.8 Coupling with Alkylboron Reagents2.1.9 Coupling with Electron-Deficient Heteroarylamines2.1.10 Selective C–N Bond Formation for the Synthesis of Heterocycle-Containing Compounds2.1.11 Using Sulfonato-imino Copper(II) Complexes2.2 C–O Bond Formation2.2.1 Coupling with (Hetero)arylboron Reagents2.2.2 Coupling with Alkyl- and Alkenylboron Reagents3 C–Element (Element = S, P, C, F, Cl, Br, I, Se, Te, At) Bond Forma tion under Modified Chan–Lam Conditions4 Conclusions

Sentence-Based Experience Logging in New Hearing Aid Users

2020 ◽  
Vol 29 (3S) ◽  
pp. 631-637
Author(s):  
Katja Lund ◽  
Rodrigo Ordoñez ◽  
Jens Bo Nielsen ◽  
Dorte Hammershøi
Keyword(s):  
Hearing Aid ◽  
Patient Experiences ◽  
Online Tool ◽  
Rehabilitation Process ◽  
Hearing Rehabilitation ◽  
Clinical Observations ◽  
Hearing Aid Use ◽  
Wide Range ◽  
Insight Into ◽  
Shed Light

Purpose The aim of this study was to develop a tool to gain insight into the daily experiences of new hearing aid users and to shed light on aspects of aided performance that may not be unveiled through standard questionnaires. Method The tool is developed based on clinical observations, patient experiences, expert involvement, and existing validated hearing rehabilitation questionnaires. Results An online tool for collecting data related to hearing aid use was developed. The tool is based on 453 prefabricated sentences representing experiences within 13 categories related to hearing aid use. Conclusions The tool has the potential to reflect a wide range of individual experiences with hearing aid use, including auditory and nonauditory aspects. These experiences may hold important knowledge for both the patient and the professional in the hearing rehabilitation process.

The Stabilizing Effect of Pre-Equilibria: A Trifluoromethyl Complex as CF2 Reservoir in Catalytic Olefin Difluorocarbenation

2020 ◽  
Author(s):  
Thomas Louis-Goff ◽  
Huu Vinh Trinh ◽  
Eileen Chen ◽  
Arnold L. Rheingold ◽  
Christian Ehm ◽  
...  
Keyword(s):  
High Selectivity ◽  
Side Reactions ◽  
Theoretical Studies ◽  
Attractive Feature ◽  
Catalyst Recovery ◽  
Wide Range ◽  
Stabilizing Effect ◽  
Experimental And Theoretical Studies

A new, efficient, catalytic difluorocarbenation of olefins to give 1,1-difluorocyclopropanes is presented. The catalyst, an organobismuth complex, uses TMSCF<sub>3</sub> as a stoichiometric difluorocarbene source. We demonstrate both the viability and robustness of this reaction over a wide range of alkenes and alkynes, including electron-poor alkenes, to generate the corresponding 1,1-difluorocyclopropanes and 1,1-difluorocyclopropenes. Ease of catalyst recovery from the reaction mixture is another attractive feature of this method. In depth experimental and theoretical studies showed that the key difluorocarbene-generating step proceeds through a bismuth non-redox synchronous mechanism generating a highly reactive free CF<sub>2</sub> in an endergonic pre-equilibrium. It is the reversibility when generating the difluorocarbene that accounts for the high selectivity, while minimizing CF<sub>2</sub>-recombination side-reactions.

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