540-51-2Relevant articles and documents
Molecular Gating of an Engineered Enzyme Captured in Real Time
Kokkonen, Piia,Sykora, Jan,Prokop, Zbynek,Ghose, Avisek,Bednar, David,Amaro, Mariana,Beerens, Koen,Bidmanova, Sarka,Slanska, Michaela,Brezovsky, Jan,Damborsky, Jiri,Hof, Martin
, p. 17999 - 18008 (2018)
Enzyme engineering tends to focus on the design of active sites for the chemical steps, while the physical steps of the catalytic cycle are often overlooked. Tight binding of a substrate in an active site is beneficial for the chemical steps, whereas good accessibility benefits substrate binding and product release. Many enzymes control the accessibility of their active sites by molecular gates. Here we analyzed the dynamics of a molecular gate artificially introduced into an access tunnel of the most efficient haloalkane dehalogenase using pre-steady-state kinetics, single-molecule fluorescence spectroscopy, and molecular dynamics. Photoinduced electron-transfer-fluorescence correlation spectroscopy (PET-FCS) has enabled real-time observation of molecular gating at the single-molecule level with rate constants (kon = 1822 s-1, koff = 60 s-1) corresponding well with those from the pre-steady-state kinetics (k-1 = 1100 s-1, k1 = 20 s-1). The PET-FCS technique is used here to study the conformational dynamics in a soluble enzyme, thus demonstrating an additional application for this method. Engineering dynamical molecular gates represents a widely applicable strategy for designing efficient biocatalysts.
Ni-Catalyzed Formal Cross-Electrophile Coupling of Alcohols with Aryl Halides
Lin, Quan,Ma, Guobin,Gong, Hegui
, p. 14102 - 14109 (2021/11/20)
Direct coupling of unactivated alcohols remains a challenge in current synthetic chemistry. We herein demonstrate a strategy building upon in situ halogenation/reductive coupling of alcohols with aryl halides to forge Csp2-Csp3 bonds. The combination of 2-chloro-3-ethylbenzo[d]oxazol-3-ium salt (CEBO) and TBAB as the mild bromination reagents enables rapid transformation of a wide range of alcohols to their bromide counterparts within one to 5 min in CH3CN and DMF, which is compatible with the Ni-catalyzed cross-electrophile coupling conditions in the presence of a chemical reductant. The present method is suitable for arylation of a myriad of structurally complex alcohols with no need for prepreparation of alkyl halides. More importantly, the mild and kinetically rapid bromination process has shown good selectivity in the bromination/arylation of symmetric diols and less sterically hindered hydroxyl groups in polyols, thus offering promise for selective functionalization of diols and polyols without laborious protecting/deprotecting operations. The practicality of this work is also evident in the arylation of a number of carbohydrates, drug compounds, and naturally occurring alcohols.
Acid-Catalyzed Intramolecular Ring-Opening Reactions of Cyclopropanated Oxabenzonorbornadienes with Carboxylic Acid Nucleophiles
Carlson, Emily,Ho, Angel,Koh, Samuel,Macleod, Matthew P.,Pounder, Austin,Tam, William
, (2021/12/02)
The present work demonstrates the ability of carboxylic acid tethered cyclopropanated oxabenzonorbornadienes (CPOBDs) to undergo ring-opening reactions in mild acidic conditions. The optimized reaction conditions involve the use of pTsOH in DCE at 90 °C. Two regioisomers are formed but the reactions are highly regioselective towards type 3 ring-opened products. It was observed that substitution at the C5 and aryl positions of CPOBD significantly hinders the ring-opening reactions leading to decreased yields of ring-opened products, although high regioselectivity for the Type 3 ring-opened products is still maintained. Herein, the first examples of acid-catalyzed intramolecular ring-opening reactions of CPOBD with carboxylic acid nucleophiles are reported.
Synthetic method of furazolidone metabolite AOZ
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Paragraph 0022-0024, (2020/07/13)
The invention discloses a preparation method of 3-amino-2-oxazolidinone (AOZ). The method comprises the following steps: 1) carrying out a reaction on ethylene glycol and PBr3 to obtain 2-bromoethanol; 2) carrying out a substitution reaction on 2-bromoethanol and an alkali, then adding hydrazine hydrate into the system, continuously carrying out a ring-opening reaction, and removing excessive 2-bromoethanol and water after the reaction is completed to obtain an intermediate 2-hydrazinoethanol; and 3) in the presence of an alkali, carrying out a reaction on 2-hydrazinoethanol and diethyl carbonate to obtain 3-amino-2-oxazolidinone (AOZ). According to the method, a nitrofuran metabolite AOZ is synthesized by adopting a one-pot method at the rear half part, so that the loss of a separated andpurified sample in the synthesis process is greatly reduced.
Synthetic method of furazolidone metabolite AOZ
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Paragraph 0028-0030, (2020/07/13)
The invention discloses a preparation method of 3-amino-2-oxazolidinone (AOZ). The method comprises the following steps: 1) carrying out a reaction on ethylene glycol and PBr3 to obtain 2-bromoethanol; 2) in the presence of an alkali, carrying out a reaction on NH2NH2Boc and 2-bromoethanol to obtain Boc protected 2-hydrazinoethanol; 3) in the presence of an alkali, carrying out a reaction on Boc protected 2-hydrazinoethanol and diethyl carbonate to obtain Boc protected 3-amino-2-oxazolidinone; and 4) performing deprotection on the Boc group in the Boc protected 3-amino-2-oxazolidinone to obtain 3-amino-2-oxazolidinone. According to the method, the yield of AOZ in the synthesis process is obviously increased, and separation and purification are facilitated.
An Ultrasensitive Fluorescence Assay for the Detection of Halides and Enzymatic Dehalogenation
Aslan-üzel, A?k?n S.,Beier, Andy,Ková?, David,Cziegler, Clemens,Padhi, Santosh K.,Schuiten, Eva D.,D?rr, Mark,B?ttcher, Dominique,Hollmann, Frank,Rudroff, Florian,Mihovilovic, Marko D.,Bury?ka, Tomá?,Damborsky, Ji?í,Prokop, Zbyněk,Badenhorst, Christoffel P. S.,Bornscheuer, Uwe T.
, p. 2032 - 2039 (2020/02/11)
Halide assays are important for the study of enzymatic dehalogenation, a topic of great industrial and scientific importance. Here we describe the development of a very sensitive halide assay that can detect less than a picomole of bromide ions, making it very useful for quantifying enzymatic dehalogenation products. Halides are oxidised under mild conditions using the vanadium-dependent chloroperoxidase from Curvularia inaequalis, forming hypohalous acids that are detected using aminophenyl fluorescein. The assay is up to three orders of magnitude more sensitive than currently available alternatives, with detection limits of 20 nM for bromide and 1 μM for chloride and iodide. We demonstrate that the assay can be used to determine specific activities of dehalogenases and validate this by comparison to a well-established GC-MS method. This new assay will facilitate the identification and characterisation of novel dehalogenases and may also be of interest to those studying other halide-producing enzymes.
1,2-Dibromotetrachloroethane: An efficient reagent for many transformations by modified Appel reaction
Essiz, Sel?uk,Da?tan, Arif
, p. 150 - 156 (2019/05/16)
An efficient and facile method has been developed for the synthesis of alkyl bromides from various alcohols under mild conditions using a triphenylphosphine (PPh 3) /1,2-dibromotetrachloroethane (DBTCE) complex in excellent yields and very short time (5 min). This method can also be applied for the transformation of chiral alcohols to their corresponding bromides in very high enantiomeric excess. The PPh 3 /DBTCE complex is also successfully applied to ring-opening reactions of cyclic ethers in mild conditions. Esterification, amidation, and formation of acid anhydrides under very mild experimental conditions are also successfully accomplished by following a modification of the Appel reaction protocol in this work.
Method for preparing halogen ethyl alcohol and ethylene oxide
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Paragraph 0097; 0098; 0109; 0110; 0130; 0131, (2017/05/19)
The invention provides a method for preparing halogen ethyl alcohol. The method comprises the following step: (1) halogen alcoholization: adding halogen hydride, H2O2, ethylene and a Ti heteroatom-containing molecular sieve into a reaction device, and carrying out halogen alcoholization reaction to obtain the halogen ethyl alcohol. The invention also provides a method for preparing ethylene oxide with a halogenohydrin method. The method comprises the following steps: (1) halogen alcoholization: adding halogen hydride, H2O2, ethylene and a Ti heteroatom-containing molecular sieve into the reaction device, and carrying out the halogen alcoholization reaction to obtain the halogen ethyl alcohol; (2) saponification: carrying out saponification reaction on the halogen ethyl alcohol in the step (1) and a hydroxide of alkali metal, and separating to obtain the ethylene oxide and alkali halide metal salt; optionally (3) electroosmosis: carrying out bipolar membrane electroosmosis on alkali halide metal salt obtained in step (2) to obtain the hydroxide of alkali metal and the halogen hydride. According to the methods, the halogen ethyl alcohol or the ethylene oxide can be prepared at extremely high selectivity and yield, and the discharging of waste water and waste residues can be drastically lowered.
Mechanism-guided design of flow systems for multicomponent reactions: Conversion of CO2 and olefins to cyclic carbonates
Wu, Jie,Kozak, Jennifer A.,Simeon, Fritz,Hatton, T. Alan,Jamison, Timothy F.
, p. 1227 - 1231 (2014/03/21)
A mechanism-guided design of a multi-step flow system enabled an efficient general process for the synthesis of cyclic carbonates from alkenes and CO 2. The flow system proved to be an ideal platform for multicomponent reactions because it was straightforward to introduce reagents at specific stages without their interacting with each other or with reaction intermediates prone to destruction by them. This system exhibited superior reactivity, increased yield, and broader substrate scope relative to conventional batch conditions and suppressed the formation of undesired byproducts, such as, epoxides and 1,2-dibromoalkanes. The Royal Society of Chemistry 2014.
Oxidative bromination of alkenes mediated with nitrite in ionic liquids
Kuznetsova, Lidia I.,Kuznetsova, Nina I.,Zudin, Vladimir N.,Utkin, Viktor A.,Trebushat, Dmitry V.,Fedotov, Martin A.,Larina, Tatyana V.
, p. 1499 - 1506,8 (2014/11/08)
The oxidative bromination of C2-C8 alkenes with HBr-NaNO2-O2 in solutions of BMImBr, HMImBr or BMImBF 4 containing 16-28 wt% H2O was studied using volumetric method, GC-MS analysis, 14N NMR and UV-VIS spectroscopy. The optimal conditions to conduct the reaction at high selectivity for 1,2-dibromoalkanes in BMImBr were determined. The composition of ionic liquid affects the catalytic performance. Although in BMImBF4 the reaction runs with equal rate as in bromide ionic liquid, the fraction of bromohydrin in the reaction products increases to 20 %. Generated from NaNO2, NOx operated as a catalyst in the oxidation of Br- and was oxidized to catalytically inert NO3 - anions when complete conversion of HBr was attained. Graphical Abstract: Oxidative bromination of alkenes [Figure not available: see fulltext.]
