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Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2′-O-glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2′-O-glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2′-O-glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2′-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2′-O-glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 Å) was solved, and mechanisms of its regio-selectivity was interpreted by pKa calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogen‒deuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7-O-glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2′-O-glycosylation (kcat/Km, 0.23 L/(s·μmol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design.

Organic electrochemistry is currently experiencing an era of renaissance, which is closely related to the possibility of carrying out organic transformations under mild conditions, with high selectivity, high yields, and without the use of toxic solvents. Combination of organic electrochemistry with alternative approaches, such as photo‐chemistry was found to have great potential due to induced synergy effects. In this work, we propose for the first time utilization of plasmon triggering of enhanced and regio‐controlled organic chemical transformation performed in photoelectrochemical regime. The advantages of the proposed route is demonstrated in the model amination reaction with formation of C−N bond between pyrazole and substituted benzene derivatives. Amination was performed in photo‐electrochemical mode on the surface of plasmon active Au@Pt electrode with attention focused on the impact of plasmon triggering on the reaction efficiency and regio‐selectivity. The ability to enhance the reaction rate significantly and to tune products regio‐selectivity is demonstrated. We also performed density functional theory calculations to inquire about the reaction mechanism and potentially explain the plasmon contribution to electrochemical reaction rate and regioselectivity. [ABSTRACT FROM AUTHOR]

Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2′- O -glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2′- O -glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2′- O -glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2′-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2′- O -glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 Å) was solved, and mechanisms of its regio-selectivity was interpreted by p K a calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogen‒deuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7- O -glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2′- O -glycosylation (k cat / K m , 0.23 L/(s·μmol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design. This work reports a novel 2′- O -glycosyltransferase, unravels its regio-selectivity mechanism, and improves its catalytic function through protein engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

[32] Palladium-catalyzed Suzuki-Miyaura cross-coupling of B 3l b with bromobenzene or iodomethane provided ( I E i )-allyl fluorides B 7 b or B 8 b in good yields without any degradation of the I E i / I Z i ratios. [39] The reaction shows a broad substrate scope of -silyl-substituted allylboronate esters, affording various ( I E i )-boryl-substituted allyl fluorides in good yields with high selectivities. Keywords: allyl fluorides; chemoselectivity; fluorodesilylation; regio-selectivity; stereoselectivity EN allyl fluorides chemoselectivity fluorodesilylation regio-selectivity stereoselectivity 2165 2168 4 10/31/23 20231127 NES 231127 Graph The selective introduction of fluorine atoms into organic molecules has emerged as a prominent research field in organic synthesis, owing to the specific physicochemical properties of organofluorines, such as improved metabolic stability and high lipophilicity. Upon treatment of B 1a b with Selectfluor ( B 2a b ) in acetonitrile at room temperature, the corresponding 1-boryl-substituted allyl fluoride B 3a b was obtained in a moderate SP 1 sp H NMR yield of 35% with an I E i / I Z i ratio of 9:1 (entry 1). [Extracted from the article]

Mostly, enzyme activity is greatly reduced after immobilization due to unfavourable conformational change occurred during the immobilization procedure. Herein, we report a novel magnetic nanoparticle-based platform for Bacillus altitudinis esterase (EstBASΔSP) immobilization using dialdehyde starch (DAS) as a molecular glue. First polydopamine (PDA) was coated on the surface of Fe3O4 nanoparticles (Fe3O4 NPs) with a controllable thickness. Thereafter, PDA-functionalized Fe3O4 NPs were modified with dialdehyde starch (DAS) to provide the aldehyde groups, which was employed as a glue to further fix the EstBASΔSP on particle surface via covalent bonding, resulting in the formation of a sea-urchin-like esterase-immobilized magnetic nanoparticle. The obtained nanoparticles (Fe3O4@PDA/DAS) achieved an enzyme load of 162.72 mg/g and retained 65.7% of its specific enzyme activity, demonstrating better thermal and storage stability compared with the "polydopamine-coated" nanoparticles (Fe3O4@PDA) and free EstBASΔSP. In addition, in a chloramphenicol palmitate synthesis, the immobilized esterase (EstBASΔSP-Fe3O4@PDA/DAS) gave 99% conversion and purity in 21 h (chloramphenicol: 0.15 M, enzyme dosage: 50 mg/mL) and retained over 80% of its activity after 12 cycles. This study provides a general strategy for immobilizing enzyme on nanoparticles and employs them as a novel platform for enzyme-mediated biocatalytic reaction. [ABSTRACT FROM AUTHOR]

The factors governing the regio-selectivity of the alkylation of adenine have been of interest for many years due to the biological importance of adenine derivatives, however, no reaction kinetic studies have been conducted. Herein, we report the rate constants and activation parameters of the benzylation of adenine under basic conditions in DMSO in the absence and presence of 15-crown-5 ether using real-time 1 H NMR spectroscopy. The reaction is second-order for the formation of the N9- and N3-benzyladenine products, with a regio-selectivity factor 2.3 in favour of the N9-adduct. The Gibbs free energy of activation amounts to 87±2 kJ mol -1 for both reactions. The formation of the N9-adduct is more activated by 7 kJ mol -1 , but its effect is offset by a less negative activation entropy, demonstrating that the long-contested reason for the regioselectivity in the benzylation of adenine is dominated by compensation of entropy and enthalpy in the transition state. The kinetic parameters obtained in the presence of the 15-crown-5 ether indicate that the crown ether forms a complex with an adenine-sodium ion-pair, increasing the activation barrier. However, the Gibbs free energy in the absence and presence of the crown ether remains constant., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Mono-2- O -tosyl-β-cyclodextrin is a key compound, as starting material, for the preparation of multifunctional systems in supramolecular chemistry. Although several methods are available in the literature for its synthesis, yields are always moderate (usually less than 42%) and reproducibility can be an issue as a result of the difficulties encountered in its preparation that are related to selectivity, monofunctionalization, solubility and purification, among others. A modification of a literature method was developed giving emphasis to simplicity and reproducibility and, for the first time, was tested with nine easily accessible tosylating reagents that differ significantly in their nature and reactivity. Product isolation was accomplished with precipitation followed by reverse-phase flash chromatography, which is easy to scale up. Interestingly, with the proposed method, all nine reagents can be successfully applied for the synthesis of the product with yields ranging from 33% to 40%. Optimum reaction times and temperatures were found and conclusions for each tosylating reagent are drawn. [ABSTRACT FROM AUTHOR]

A novel and practical method to synthesize trifluoromethyl tertiary alcohols has been developed. Under mild reaction conditions, the present reaction could be compatible with a wide range of functional groups. Moreover, the performance of gram-scale reaction and further transformations illustrated the good potential utility of the present chemistry. Furthermore, the radical process of this reaction has been proved by mechanistic studies. [ABSTRACT FROM AUTHOR]

Current studies were performed to review the synthesis and yield enhancement of ortho-nitrophenol in the presence of phase-transfer catalysts. Selective synthesis and yield enhancement of ortho-nitrophenol can be varied in the presence of phase-transfer catalysts under different synthetic mechanisms. The phenols and substituted phenols can be selectively nitrated at their ortho/para positions by direct or indirect nitration and by varying the reaction parameters such as dilution of acid, substrate and the strength of the catalyst. High selectivity can be achieved by indirect nitration with diluted nitric acid in the presence of tetra-butyl ammonium bromide (TBAB) and acetyl trimethylammonium bromide (CTAB). TBAB has been reported to be the most effective catalyst for the conversion of phenolic compounds into o-nitrophenol. However, this regio-selectivity will be reversed to para-position by using sodium bromide as a surfactant. The use of nitronium tetra fluoroborate suspended in acetonitrile process gives highest regio-selective nitration with a 95% yield of ortho product. Performing the nitration under sonication conditions lowers the reaction time and increases the ortho/para regio-selectivity. Under sonication conditions, maximum conversion into ortho derivative (95%) is achieved by using TBAB as catalyst in 20 min but maximum para-selectivity is achieved by using CTAB and NaBr catalysts. The use of PdCl2, Pd(PPh3)2Cl2 and Pd(OAc)2, H-beta zeolite, catalysts for selective nitration has also been reported. Greater than 85% yield of o-nitrophenol was observed by using microwaves system technology. [ABSTRACT FROM AUTHOR]

Esterase belongs to hydrolase class of enzyme which catalyses the breakdown and creation of the ester bond. Due to its properties like regio-selectivity, stereo-specificity and stability in organic solvents, esterase is widely used in industrial processes. Esterases have applications in food industry, paper industry, notably in degradation of plastics and pesticides and for the synthesis of optically pure compounds. One of the toughest tasks is upholding the structural stability of enzyme for the duration of any biochemical reaction. Immobilization provides solution for this problem. Immobilization is the restraining of enzyme to a support. With the recent advances in technology, the use of new approach like nanoparticles, magnetic nanoparticles and cross-linked enzyme aggregates (CLEAs) is preferred by researchers. Nanoparticles provide better stability, multi-functionality and higher surface area for immobilization. Current review comprises of various methods used in immobilization of esterase and applications of esterase. [ABSTRACT FROM AUTHOR]

Amaryllidaceae alkaloids are a diverse group of alkaloids exclusively reported from the Amaryllidaceae plant family. In planta, their biosynthesis is still not fully characterized; however, a labeling study established 4'-O-methylnorbelladine as the key intermediate compound of the pathway. Previous reports have characterized O-methyltransferases from several Amaryllidaceae species. Nevertheless, the formation of the different O-methylnorbelladine derivatives (3'-O-methylnorbelladine, 4'-O-methylnorbelladine, and 3'4'-O-dimethylnorbelladine), the role, and the preferred substrates of O-methyltransferases are not clearly understood. In this study, we performed the biochemical characterization of an O-methyltransferase candidate from Narcissus papyraceus (NpOMT) in vitro and in vivo, following biotransformation of norbelladine in Nicotiana benthamiana having transient expression of NpOMT. Docking analysis was further used to investigate substrate preferences, as well as key interacting residues of NpOMT. Our study shows that NpOMT methylates norbelladine preferentially at the 4'-OH position in vitro and in planta. Interestingly, NpOMT also catalyzed the synthesis of 3',4'-O-dimethylnorbelladine from norbelladine and 4'-O-methylnorbelladine during in vitro enzymatic assay. Furthermore, we show that NpOMT methylates 3,4-dihydroxybenzylaldehyde and caffeic acid in a nonregiospecific manner to produce meta/para monomethylated products. This study reveals a novel catalytic potential of an Amaryllidaceae O-methyltransferase and its ability to regioselectively methylate norbelladine in the heterologous host N. benthamiana., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nucleosides play a pivotal role in biological systems and therefore have attracted a lot of interest as chemotherapeutic agents in drug discovery. Over the years biocatalysts have emerged as a sustainable alternative to conventional synthetic catalysts. As a nature's catalyst, they exhibit excellent selectivity, remarkable tolerance, and help in carrying out eco-friendly benign processes. The use of a biocatalyst as a regio- and enantioselective catalyst is particularly relevant in the transformations of nucleosides and their analogs because of the presence of multiple chiral centres. Herein, we discuss the recent advances in the Pseudomonas Cepacia Lipase mediated selective acylation and deacylation reactions of the secondary hydroxyl and amino groups of nucleosides and their analogs. [ABSTRACT FROM AUTHOR]

Yndiamides, N , N -disubstituted alkynes, are versatile building blocks for the synthesis of nitrogen-containing organic molecules. Unlike ynamides, relatives that are inherently polarized by a single nitrogen substituent, their pseudo -symmetric nature renders regioselective reactions challenging. Here we report investigations into the regio-selective addition of Brønsted acids to non-symmetric yndiamides, a reaction that delivers N , O , N - and N , S , N -trisubstituted ketene acetals with excellent regio- and stereoselectivity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A lipase gene from Serratia sp. W3 (SmL) was expressed in E. coli and purified. • The specific activity of the rSmL was around 12-fold than that of the native SmL. • rSmL efficiently hydrolyzed triglycerides with short and medium chain fatty acids. • SmL exhibited a clear regio-preference toward the sn -3 position of triglycerides. A recombinant Serratia sp. W3 lipase (rSmL) was expressed in E. coli and purified to homogeneity. The kinetic properties, regio-selectivity, and interfacial performances of rSmL were compared with those of the native lipase (nSmL). rSmL has a molecular mass of 67 kDa and a specific activity of 3530 U mg−1 which is around 12-fold higher than that of nSmL (300 U mg−1) when using olive oil as the substrate. Both rSmL and nSmL were able to hydrolyze the ester bond at the sn -1 and sn -3 positions but exhibited a clear regio-preference towards the sn -3 position of the surface-coated triglycerides (TG), which were esterified with α-eleostearic acid at the sn -1/3 position or dicaprin isomers spread as monomolecular films. Molecular modeling and docking of TG into the active site of rSmL indicated that this regio-preference may be due to steric hindrance, created by the residues Ile308 and Trp311, with distances between the sn- 1 reactive carbon and the catalytic Serine residue ranging from 3.15 to 5.47 Å. In contrast, the sn -3 positioning within the enzyme catalytic pocket resulted in shorter distances, ranging from 2.79 to 4.15 Å, therefore facilitating the hydrolysis at the sn -3 position. [ABSTRACT FROM AUTHOR]

• A convenient method to prepare N-acyl norepinephrine derivatives has been developed, one of which (R = CH 3) was an important active ingredient isolated from Aspongopus chinensis Dallas. • The mechanism of key step was investigated and the structure was identified by X-ray spectra. • This protocol has several advantages, including two-step, moderate to good yield and regioselective. A convenient method to prepare (±)-N-acyl norepinephrine derivatives has been developed, one of which (R = CH 3) was an important active ingredient isolated from Aspongopus chinensis Dallas. To full acylated norepinephrine 3 , different de-protection conditions will afford different products (4 or 5) selectively. The structure was identified by 1H NMR, 13C NMR, HRMS and X-ray spectra. [Display omitted] [ABSTRACT FROM AUTHOR]

Nucleosides are valuable biologically active compounds, which display antitumour and antiviral activities. Various types of bioactive nucleosides are designed to improve their therapeutic efficacy, However this strategy faces the difficult selectivity issues of nucleoside chemistry. Therefore, the goal of this review is to give an idea of the opportunities provided by biocatalyst CAL-B procedures in the preparation of different types of bioactive nucleoside compounds. The function of Candida Antarctica lipase-B (CAL-B) in organic synthesis is reviewed. This enzyme has been found to be a principally efficient and robust lipase catalyzing an unexpected variety of reactions including many different regio- chemo, and diastereo-selective synthesis. Moreover, the structure of Candida Antarctica lipase-B is an example of an enzyme for which its specificity has been predicted based on acylation and deacylation mechanism on substrates. [ABSTRACT FROM AUTHOR]

Abstract The carbon-oxygen bond activation (COA) of epoxides with rhodium(II) and rhodium (III) porphyrins have been examined. RhIII(ttp)H (1) (ttp = 5,10,15,20-tetratolylporphyrinato dianion) was found to cleave the less sterically hindered carbon-oxygen bond of epoxides selectively at room temperature under neutral conditions to generate the stoichiometric COA product rhodium porphyrin β -hydroxyl alkyls in moderate to good yields. Graphical abstract [RhII(ttp)] 2 metalloradical catalyzed the 1,2-insertion of epoxides with RhIII(ttp)H at room temperature under neutral conditions to give the rhodium porphyrin β -hydroxyl alkyls complexes in moderate to good yields. Image 1 Highlights • The C O bond cleavage of epoxide with Rh porphyrin hydrido complex, catalyzed by Rh porphyrin metalloradical, was achieved. • The C O bond cleavage was carried out under neutral conditions at room temperature. • The C O bond cleavage with rhodium porphyrin hydrido complex was regio-selective. [ABSTRACT FROM AUTHOR]

Abstract Presence of cyclobutane rings in bioactive natural products makes them a popular synthetic target. Most common strategy for synthesizing cyclobutanes is [2+2] cycloaddition, which is usually facilitated by using ultraviolet radiation and catalysts. Herein we report the design and synthesis of densely functionalized cyclobutanes by alleviating these drawbacks and using sunlight. Further, we identified the putative mechanism of the transformation based on kinetic, fluorescence and crystallographic studies and evaluated biological activities of the products against MCF7 cell lines. The rational design of the olefinic substrates was based on their UV–vis spectra. The generic aspect of the reaction was elucidated by the syntheses of diverse analogs of cyclobutanes. Further, crystal structures and UV–vis spectra of the olefinic partners assisted us in rationalizing the stereoselectivity of the heterodimers. We believe this energy-efficient mild approach will provide a substantial contribution to the existing repertoire of strategies to regio- and stereoselectively access cyclobutanes. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Chiral BINOL-derived pyrophosphoric acid catalysts were developed and used for the regio- and enantioselective aza-Friedel--Crafts reaction of phenols with aldimines. ortho/para-Directing phenols could react at the para-position selectively with moderate to good enantioselectivities. Moreover, the gram-scale transformation of a product into the key intermediate for the antifungal agent (R)-bifonazole was demonstrated. [ABSTRACT FROM AUTHOR]

The polyether ionophore salinomycin has recently captured much interest due to its potent activity against multi-drug resistant cancer cells and cancer stem cells. Previous studies have shown that either acylation of the C20 position or esterification/amidation of the C1 carboxylate moiety is beneficial in terms of biological properties. In this paper, we present the first analogs combining such modifications. Evaluation of the anti-proliferative activity against a series of cancer cell lines showed that acylation of the C20 hydroxyl group improves the activity of salinomycin C1 amides but not of the corresponding C1 esters. Importantly, the activity of several of the doubly modified analogs surpasses that of commonly used cytostatic drugs cisplatin and doxorubicin in the LoVo/DX multi-drug resistant cell line. All analogs were tested against primary acute lymphoblastic leukemia cells in standard cell viability assays; three were more potent than salinomycin. Further studies revealed that selected analogs induced characteristics of apoptotic cell death and increased expression of p53. Additionally, using an ex vivo model of breast tumor, tumor cell viability significantly decreased after treatment with salinomycin or its double-modified derivative ( 3a ) in a time-dependent manner. The present findings indicate that double-modified salinomycin derivatives constitute promising lead compounds for targeting various types of cancer. [ABSTRACT FROM AUTHOR]

A novel series of bis(tetrahydro[1,2,4]triazolo[5,1- b]quinazolin-8(4 H)-ones) were prepared in a regioselective manner via a three component reaction of bis-aldehydes with 5-amino-1,2,4-triazole and dimedone under microwave irradiation as well as under conventional heating. The reactions were carried out in the absence as well as in the presence of ZnO nanoparticles as a heterogeneous catalyst. Best results were achieved when these reactions were carried out under MW heating. The presence of ZnO nanoparticles was found to improve the yields of the reactions but did not change the regioselectivity the products. The reaction mechanism and the unambiguous structural elucidation of the expected regioisomers were studied using DFT calculations as well as 2D-HMBC spectroscopy. Graphical abstract: [ABSTRACT FROM AUTHOR]

Cytochrome P450 enzymes are increasingly investigated due to their potential application as biocatalysts with high regio- and/or stereo-selectivity and under mild conditions. Vitamin D3 (VD3) metabolites are of pharmaceutical importance and are applied for the treatment of VD3 deficiency and other disorders. However, the chemical synthesis of VD3 derivatives shows low specificity and low yields. In this study, cytochrome P450 CYP109A2 from Bacillus megaterium DSM319 was expressed, purified, and shown to oxidize VD3 with high regio-selectivity. The in vitro conversion, using cytochrome P450 reductase (Bm CPR) and ferredoxin (Fdx2) from the same strain, showed typical Michaelis-Menten reaction kinetics. A whole-cell system in B. megaterium overexpressing CYP109A2 reached 76 ± 5% conversion after 24 h and allowed to identify the main product by NMR analysis as 25-hydroxylated VD3. Product yield amounted to 54.9 mg·L−1·day−1, rendering the established whole-cell system as a highly promising biocatalytic route for the production of this valuable metabolite. The crystal structure of substrate-free CYP109A2 was determined at 2.7 Å resolution, displaying an open conformation. Structural analysis predicts that CYP109A2 uses a highly similar set of residues for VD3 binding as the related VD3 hydroxylases CYP109E1 from B. megaterium and CYP107 BR1 (Vdh) from Pseudonocardia autotrophica. However, the folds and sequences of the BC loops in these three P450s are highly divergent, leading to differences in the shape and apolar/polar surface distribution of their active site pockets, which may account for the observed differences in substrate specificity and the regio-selectivity of VD3 hydroxylation. Database The atomic coordinates and structure factors have been deposited in the Protein Data Bank with accession code (substrate-free CYP109A2). Enzymes Cytochrome P450 monooxygenase CYP109A2, , UniProt ID: , Ferredoxin, UniProt ID: , cytochrome P450 reductase, , UniProt ID: . [ABSTRACT FROM AUTHOR]

Background The backbone structure of many hemicelluloses is acetylated, which presents a challenge when the objective is to convert corresponding polysaccharides to fermentable sugars or else recover hemicelluloses for biomaterial applications. Carbohydrate esterases (CE) can be harnessed to overcome these challenges. Methods Enzymes from different CE families, An AcXE (CE1), Os AcXE (CE6), and Mt AcE (CE16) were compared based on action and position preference towards acetyl-4- O -methylglucuronoxylan (MGX) and acetyl-galactoglucomannan (GGM). To determine corresponding positional preferences, the relative rate of acetyl group released by each enzyme was analyzed by real time 1 H NMR. Results An AcXE (CE1) showed lowest specific activity towards MGX, where Os AcXE (CE6) and Mt AcE were approximately four times more active than An AcXE (CE1). Mt AcE (CE16) was further distinguished by demonstrating 100 times higher activity on GGM compared to An AcXE (CE1) and Os AcXE (CE6), and five times higher activity on GGM than MGX. Following 24 h incubation, all enzymes removed between 78 and 93% of total acetyl content from MGX and GGM, where Mt AcE performed best on both substrates. Major conclusions Considering action on MGX, all esterases showed preference for doubly substituted xylopyranosyl residues (2,3- O -acetyl-Xyl p ). Considering action on GGM, Os AcXE (CE6) preferentially targeted 2- O -acetyl-mannopyranosyl residues (2- O -acetyl-Man p ) whereas An AcXE (CE1) demonstrated highest activity towards 3- O -acetyl-Man p positions; regiopreference of Mt AcE (CE16) on GGM was less clear. General significance The current comparative analysis identifies options to control the position of acetyl group release at initial stages of reaction, and enzyme combinations likely to accelerate deacetylation of major hemicellulose sources. [ABSTRACT FROM AUTHOR]

In the present article, the mechanism of 1,6-enyne cycloisomerization catalyzed by the planar Au 8 cluster was investigated in details by means of density functional theory. The effects of the size and shape of the gold nanoclusters (Au 7-20 ) on their catalysis of 1,6-enyne cycloisomerization were also studied. The computational results indicate that the main reaction channels of the 1,6-enyne cycloisomerization on the Au 8 cluster are the 5–exo–anti–cycloisomerization, and the single cleavage pathway is slightly more feasible than the double cleavage pathway. The selectivity of 1,6-enyne cycloisomerization catalyzed by the gold clusters is controlled by the orbital interaction between the gold atoms and the carbene fragment in the migration of CH 2 group. In addition, the influence of coordinate environment of the gold atoms on adsorption energy, catalytic activity, and regio-selectivity were amply interpreted as well. [ABSTRACT FROM AUTHOR]

Highly regio-selective cyanation of vicinal ( Z )-dibromoalkenyl silanes was achieved by a vinylic Rosenmund-von Braun reaction, significantly suppressing side-production of alkyne. The alkyne was generated by a halogen elimination side-reaction that is an intrinsic problem in metal-activation of vicinal dihaloalkenes. We have studied to overcome the problem, and finally found the combination of CuCN and O = PPh 3 in toluene solvent effectively controlled the production of byproducts. The resultant single isomer has significance in potentially application as a multi-tunable synthetic scaffold. [ABSTRACT FROM AUTHOR]

An efficient and facile two-step strategy for the synthesis of ( Z )-aurone from arylacetylenes and salicyladehydes, via silver(I) nitrate mediated cyclization/oxidation in the presence of potassium carbonate has been developed. The key feature of our method was delicate cascade reaction, to provide the corresponding ( Z )-aurone in high yield and good regio- and stereo selectivity. [ABSTRACT FROM AUTHOR]

A multi-component, one pot and regio-selective synthesis of different 5-substituted 1 H-tetrazoles was successfully accomplished via a click reaction. In this respect, we have performed the reaction of either isatins or various aromatic aldehydes with malononitrile and ionic liquid, 1-butyl-3-methylimidazolium azide ([BMIM]N), as a relatively green source of azide mediated by o-phthalimide- N-sulfonic acid (OPNSA). The calculated thermodynamic results demonstrate a reliable agreement with our experimentally observed regio-selectivity. From the electronic viewpoint, we have also assessed the nature of regio-selectivity via quantum theory of atoms in molecule analysis. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Density functional studies are performed to understand the role of chelating bi-phosphine ligands [(Ph P(CH )PPh ); m = 1-4] in modulating the regio-selectivity of benzoic acid addition to 1-hexyne, in presence of ruthenium(II) catalyst [(Ph P(CH )PPh )Ru(methallyl) ]. The Markovnikov addition to 1-hexyne is observed when catalyst 1 [(Ph P(CH )PPh )Ru(methallyl) ] is employed, whereas a reverse regio-selectivity is witnessed in presence of 1 [(Ph P(CH )PPh )Ru(methallyl) ]. Anti-Markovnikov addition occurs via the neutral vinylidene intermediates ( 5) formed after 1,2-hydrogen shift in hexyne coordinated ruthenium(II) complexes 3. The energy profile shows clear preference for Markovnikov addition by 15.0 kcal/mol ( ${\Delta } G_{\mathrm {L}}^{S})$ in case of catalyst system 1. In contrast, anti-Markovnikov pathway following neutral vinylidenes are more favourable by 9.1 kcal/mol ( ${\Delta } G_{\mathrm {L}}^{S})$ for catalyst system 1. The Z-enol ester formation is more predominant in the anti-Markovnikov pathway since the activation barrier for this step requires less energy (5.9 kcal/mol, ${\Delta } G_{\mathrm {L}}^{S})$ than the one furnishing the E-product. The calculated results are in good agreement with the reported experimental findings. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Phenylhydrazine reacted regioselectively with 6-substituted 4-pyrone-2-carboxylic acids (or esters) in protic and aprotic solvents, leading to phenylhydrazones of 3-(3-R-1-phenylpyrazol-5-yl)- or 3-(5-R-1-phenylpyrazol-3-yl)pyruvic acids (or esters), respectively. 6-Di(tri)fluoromethylcomanic acids (or esters) reacted analogously, forming the corresponding phenylhydrazones with R group in the side chain. The obtained phenylhydrazones underwent Fischer reaction under acidic conditions, forming the respective 3-(N-phenylpyrazolyl)indoles. In contrast to comanic acid and its ester, the reactions of 2-substituted 4-pyrones occurred non-selectively and gave mixtures of regioisomeric pyrazoles with phenylhydrazone group in the side chain or 3-(N-phenylpyrazolyl)indoles. A mechanism was proposed to explain the effect of solvent on the course of reaction. [ABSTRACT FROM AUTHOR]

The regio-specific hydroxylation at the 4th N-methyl leucine of the immunosuppressive agent cyclosporin A (CsA) was previously proposed to be mediated by a unique cytochrome P450 hydroxylase (CYP), CYP-sb21 from the rare actinomycetes Sebekia benihana. Interestingly, a different rare actinomycetes species, Pseudonocardia autotrophica, was found to possess a different regio-selectivity, the preferential hydroxylation at the 9th N-methyl leucine of CsA. Through an in silico analysis of the whole genome of P. autotrophica, we describe here the classification of 31 total CYPs in P. autotrophica. Three putative CsA CYP genes, showing the highest sequence homologies with CYP-sb21, were successfully inactivated using PCR-targeted gene disruption. Only one knock-out mutant, ΔCYP-pa1, failed to convert CsA to its hydroxylated forms. The hydroxylation activity of CsA by CYP-pa1 was confirmed by CYP-pa1 gene complementation as well as heterologous expression in the CsA non-hydroxylating Streptomyces coelicolor. Moreover, the cyclosporine regio-selectivity of CYP-pa1 expressed in the ∆CYP-sb21 S. benihana mutant strain was also confirmed unchanged through cross complementation. These results show that preferential regio-specific hydroxylation at the 9th N-methyl leucine of CsA is carried out by a specific P450 hydroxylase gene in P. autotrophica, CYP-pa1, setting the stage for the biotechnological application of CsA regio-selective hydroxylation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Regio- and chemo-selectivity of CALB lipase toward peptide acylation was studied. [•] An acyl-enzyme model was built and used as target to dock Lys-based peptides. [•] Models predicted the N-ɛ acylation of the lysine whatever the peptidic sequence. [•] Selectivity predictions were in accordance with experimental data. [•] The cavity shape was shown to be the main factor guiding the selectivity. [ABSTRACT FROM AUTHOR]

A highly regio-selective Povarov reaction of an aromatic aldehyde, 1 H-indazol-5-amine, and methyl 3-oxobutanoate catalyzed by iodine is described. This novel reaction selectively gave 3 H-pyrazolo[4,3- f]quinolin-9-yl acetates, in high yield, rather than 3 H-pyrazolo[4,3- f]quinoline-8-carboxylate derivatives. This procedure has the advantages of mild reaction conditions, high yields, metal-free catalyst, and high regio-selectivity. [ABSTRACT FROM AUTHOR]

Abstract: Mycelium of the basidiomycete Pleurotus sapidus known to contain a novel dioxygenase was used for the bioconversion of car-3-ene [I]. After 4h of incubation 25.3mgL−1 car-3-en-5-one [V], 5.4mgL−1 car-3-en-2-one [VII], and 7.3mgL−1 car-2-en-4-one [XV] accumulated as major oxidation products. The identity of the respective carenones and their corresponding alcohols was confirmed by comparison with MS and NMR spectral data obtained for synthesized authentic compounds. The peak areas of oxidation products were at least five times higher as compared with autoxidation. A radical mechanism similar to lipoxygenase catalysis was proposed and substantiated with detailed product analyses. The reduction of assumed car-3-ene hydroperoxides to the corresponding alcohols evidenced the radical initiated formation of hydroperoxides and confirmed the regio- and stereo-selectivity of the dioxygenase. The introduction of molecular oxygen into the bicyclic car-3-ene [I] molecule occurred at allylic positions of a cyclic isopentenyl moiety with a pronounced preference for the position adjacent to the non-substituted carbon atom of the C–C-double bond. This co-factor independent selective oxygenation presents an alternative to P450 mono-oxygenase based approaches for the production of terpene derived flavor compounds, pharmaceuticals and other fine chemicals. [Copyright &y& Elsevier]

A series of pyrazole-4-carboxylates have been synthesised using indium bromide catalyst and the cyclisation of respective 3-substituted-isoquinolinylhydrazines 1 into their corresponding ethyl-2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoates 3 in ethanol solvent under ultrasonic irradiation at 90 °C for 30 min. The regio-selective cyclisation products were efficiently provided by indium bromide catalyst and are confirmed by nuclear Overhauser effect spectroscopy-nuclear magnetic resonance (NOESY-NMR) studies. [ABSTRACT FROM AUTHOR]

Novel C-17-chloro-substituted derivative of vinorelbine or vinflunine has been regio-selectively synthesized via the chlorination reaction in the presence of Lewis acid. The catalyst CpTiCl plays a key role in the chlorination reaction. [ABSTRACT FROM AUTHOR]

Abstract: gem-Difluoromethylene substituted molecules constitute a distinct class of fluorinated compounds. In this study, special chemistry has been developed for their preparation based on the highly selective terminal hydroxylation of these gem-difluorinated octanes by AlkB (alkane hydroxylase) from Pseudomonas putida Gpo1 to form gem-difluorinated octan-1-ols. The hydroxylation reaction is performed by whole-cell catalysis. Identification of the distal- and proximal-hydroxylation products was made by 1H, 13C, and 19F NMR; GC and GC/MSD; and/or by comparison with authentic standards in GC. To the best of our knowledge, we have obtained the first synthesis of 2,2-, 3,3- and 4,4-difluorooctan-1-ols, from simple and inexpensive starting materials. [Copyright &y& Elsevier]

Abstract: Computations of ene reactions between propene and different enophiles bearing C(where X=CH2, SiH2, NH, PH, O and S) were carried out at different levels of theory. Relation between the HOMO–LUMO energy gap and electronegativity of heteroatom in X group with the activation energy were computed at CCSD/aVDZ level of theory. Regioselectivity of the reaction at CCSD/aVDZ is also estimated. Nucleus Independent Chemical Shift values of the transition states were computed at B3LYP/aVDZ to estimate the Mobius aromaticity. [Copyright &y& Elsevier]

Using open-structure (nanoporous) solids, advantage may be taken of single-site catalytically active centres to effect an enormous range of conversions of organic compounds where regio-selectivity and shape-selectivity loom large. When the single-site active centres are accommodated within a well-defined nanospace (typically pores of ca 30 Å diameter), uniquely powerful enantio-selective conversions may also be achieved; thus organometallic complexes, composed of cheap (nitrogen-based) chiral ligands anchored to the concave walls of the nanoporous solid, are especially powerful enantio-selective hydrogenation catalysts for pharmaceutically significant precursor species. The design, characterization and performance of single-site nanoporous catalysts are described and their application in (1) aerobic, shape-selective oxidation of cyclohexane to adipic acid; (2) region-specific oxidation of linear alkanes; (3) bromine-free synthesis of terephthalic acid from p-xylene using air as oxidant; (4) the in situ generation of hazardous reagents for Baeyer–Villiger oxidation of ketones to lactones and for the epoxidation of olefins; and (5) the single-step production of ε-caprolactam from cyclohexanone are outlined. Atomically engineered, multinuclear nanoparticle (bimetallic) catalysts are also described and their application in (1) one-step, solvent-free hydrogenation of polyenes; (2) asymmetric synthesis of pharmaceutical intermediates; (3) region-selective and stereo-selective allylic aminations; (4) single-step hydrogenation of dimethyl tererpthalate to 1,4-cyclohexane-dimethanol; and (5) renewable nylons from glucose and its biocatalytic derivatives is summarized. The key features of these solid catalysts (which facilitate separation of products from reactants) are that (a) they dispense with the use of corrosive reagents (and often of solvents); (b) permit the replacement of aggressive oxidants (e.g. HNO3, CrO3, etc) or even H2O2 and alkyl hydroperoxides, with molecular oxygen as the oxidant, thereby facilitating use of low-temperature and otherwise environmentally benign processes; (c) they are generally stable and recyclable and require no chemical initiators; and (d) they offer significant processing advantages in large scale and industrial operations when compared to homogeneous catalysts, especially in the generation of vital intermediates (surfactants, detergents, pharmaceuticals, polymers, perfumes and cosmetics). Typically, just one of the products (nylon-6), made by the “green”, environmentally benign bifunctional catalysts described herein, is in great demand industrially for the manufacture of (i) apparel and other textiles; (ii) floor coverings; (iii) industrial yarns; (iv) engineering plastics and (v) films for food and industrial packaging. [ABSTRACT FROM AUTHOR]

Abstract: Metallocene complexes of type MCH(TMS)2 (Cp′=η5-Me5C5, M=Y, Sm), Me2SiSmCH(TMS)2 (Cp″=η5-Me4C5) catalyze rapid and clean hydrosilylation of CH2 ph name="sbnd" />SiMe2R (R=Me, Ph, NMe2, O t Bu) with PhSiH3. The distribution of 1,2-addition product versus 2,1-addition product was found to be sensitive to both catalysts and substrates. Generation of 2,1-addition product can best be achieved by use of more sterically accessible catalysts as well as substrates containing tethering functional groups. A four-centered transition state is invoked to explain these effects. Display Omitted [Copyright &y& Elsevier]

Abstract: The coupling of trifluoromethylated 1,3-diketones with (het)aryldiazonium chlorides results mainly in the formation of 1,2,3-triketones 2-(het)arylhydrazones while using hetarylamine with a NH-group at the α-position of the heterocycle as the diazonium component gives 4,7-dihydroazolo[5,1-c]triazines due to cyclization at the trifluoroacetyl fragment. Trifluoromethylated 1,2,3-triketones 2-(het)arylhydrazones and 7-hydroxy-4,7-dihydroazolo[5,1-c]triazines react regio-selectively with methyl hydrazine and phenyl hydrazine to form 3-CF3-pyrazoles. The long-range coupling constants (J F-H) of 1-methylpyrazoles and the chemical shifts of trifluoromethyl groups in the 19F NMR spectra can be used for the determination of regio-isomeric structures of mono(trifluoromethyl)-substituted pyrazoles. 2-(Het)arylhydrazones and 4,7-dihydroazolo[5,1-c]triazines with two trifluoromethyl substituents afford the mixtures of cis- and trans-azopyrazoles in the reactions with hydrazines. [Copyright &y& Elsevier]

Abstract: o-Xylene is nitrated in liquid phase with high regio-selectivity using beta zeolite as a catalyst with stoichiometric quantity of nitric acid. The use of acetic anhydride is completely eliminated with almost zero emission of effluents. There is no formation of oxygenates or side chain nitration. The influence of experimental conditions like effect of solvent, rate of addition of nitric acid, effect of SiO2/Al2O3 ratios, are also investigated. The process is eco-friendly and less expensive and represents a clean synthesis of nitro aromatic compounds with higher regio-selectivity. [Copyright &y& Elsevier]

Abstract: Iridium-catalyzed borylation of phenacenes with bis(pinacolato)diboron proceeds either in an edge-selective manner for diborylation or an edge/side-selective manner for tetraborylation. Multiply borylated [n]phenacenes (n =3–5) were synthesized in reasonable yields. [Copyright &y& Elsevier]

Catalytic interactions of CYP3A4 with large-size ligands have been studied on the Template established in our previous studies using polyaromatic hydrocarbon and steroid ligands (DMPK 34: 113-125 and 351-364 2019 and in press 2020). Typical CYP3A4-substrates including erythromycin, cyclosporin A (ca.1200 Da), ivermectin B1a and taxanes were applied successfully and regioselective metabolisms of these ligands were reconstituted faithfully on Template. These results suggest the applicability of CYP3A4 Template throughout broadened sizes of CYP3A4 ligands. Macrolide antibiotics showed distinct degrees of tight sittings in Width-gauge, a tool for accommodation measure. The observed differences were associated with different inhibitory/inactivation potentials of troleandomycin, erythromycin, clarithromycin and azithromycin, suggesting CYP3A4 Template also as a tool for drug-interaction mechanisms. Slight expansion of Template area was made at near Site of oxidation from simulation results of antitumor agent, rilpivirine, in the present study. Ligand entry from left side of Template is also suggested from macrolide interactions. Broadened applicability of the refined CYP3A4 Template were assured with experiments with various large-size ligands., (Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)