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The tert‐butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol−1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert‐butyl C−H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro‐tert‐butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese‐oxo species that effectively oxidizes tert‐butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site‐selective and product chemoselective hydroxylation of the tert‐butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late‐stage hydroxylation at tert‐butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert‐butyl as a potential functional group in strategic synthetic planning for complex molecular architectures. [ABSTRACT FROM AUTHOR]

The tert‐butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol−1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert‐butyl C−H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro‐tert‐butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese‐oxo species that effectively oxidizes tert‐butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site‐selective and product chemoselective hydroxylation of the tert‐butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late‐stage hydroxylation at tert‐butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert‐butyl as a potential functional group in strategic synthetic planning for complex molecular architectures. [ABSTRACT FROM AUTHOR]

Three types of smectite with various crystallochemical compositions and interlayer cations as well as kaolinite and illite were fired at 800°C and 650°C and tested for their rehydroxylation's (RHX) potential and kinetics in the presence of water vapor at 200°C–350°C. A dehydroxylated structure of 2:1 Al‐rich mineral with the interlayer pillared by a large cation (like K+ or Cs+) is wide enough to allow H2O diffusion which results in advanced RHX, that is, restoring up to several tens of percent of the original OH content. Such 2:1 layer structures (beidellite, illite) do not follow the time‐to‐the‐quarter (TTTQ) kinetics during RHX and show a non‐Arrhenius behavior for isothermal RHX. Because TTTQ kinetics is assumed in an RHX dating of ceramic artifacts in archaeometry, fired‐clay ceramics prepared from material dominated by Al‐rich 2:1 minerals was found unfeasible for RHX dating. Kaolinite and Mg2+‐ or Ca2+‐exchanged smectites show the Arrhenius behavior and follow the TTTQ kinetics of RHX, resulting in apparent Ea increase with the progress of reaction (up to α ∼0.2) of ∼20–50 kJ/mol in beidellite and 15–35 kJ/mol in montmorillonite. We suggest using 'hydroxylation' rather than 'rehydroxylation' for structurally‐disordered fired clays gaining OH groups in an unknown position. [ABSTRACT FROM AUTHOR]

The hydroxylation of remote C(sp3)−H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high‐value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)−H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α‐ketoglutarate‐dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Crystal structure analysis, molecular dynamics simulations, and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on these results, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L‐Homoleucine (5 a) was reversed from the γ site (1 : 12) to the δ site (>99 : 1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)−H bonds, but also provides a theoretical guidance for the precision‐driven modification of similarly remote C(sp3)−H bonds in complex molecules. [ABSTRACT FROM AUTHOR]

Lytic polysaccharide monooxygenases (LPMOs) are Cu‐dependent metalloenzymes that catalyze the hydroxylation of strong C−H bonds in polysaccharides using O2 or H2O2 as oxidants (monooxygenase/peroxygenase). In the absence of C−H substrate, LPMOs reduce O2 to H2O2 (oxidase) and H2O2 to H2O (peroxidase) using proton/electron donors. This rich oxidative reactivity is promoted by a mononuclear Cu center in which some of the amino acid residues surrounding the metal might accept and donate protons and/or electrons during O2 and H2O2 reduction. Herein, we utilize a podal ligand containing H‐bond/proton donors (LH2) to analyze the reactivity of mononuclear Cu species towards O2 and H2O2. [(LH2)CuI]1+ (1), [(LH2)CuII]2+ (2), [(LH−)CuII]1+ (3), [(LH2)CuII(OH)]1+ (4), and [(LH2)CuII(OOH)]1+ (5) were synthesized and characterized by structural and spectroscopic means. Complex 1 reacts with O2 to produce 5, which releases H2O2 to generate 3, suggesting that O2 is used by LPMOs to generate H2O2. The reaction of 1 with H2O2 produces 4 and hydroxyl radical, which reacts with C−H substrates in a Fenton‐like fashion. Complex 3, which can generate 1 via a reversible protonation/reduction, binds H2O and H2O2 to produce 4 and 5, respectively, a mechanism that could be used by LPMOs to control oxidative reactivity. [ABSTRACT FROM AUTHOR]

Herein, a new method has been developed for the synthesis of various α‐hydroxyacetophenones via an electro‐oxidation process. It involves electrocatalytic hydroxylation via debromination of C(sp3)−Br bond. Here, simultaneous breaking of carbon‐bromine (C−Br) bond and formation of a new carbon‐oxygen (C−O) bond has been achieved through electrolysis of H2O using binary mixture of water and DMSO. The protocol features easy performance, oxidant and base‐free mild conditions and short reaction time. [ABSTRACT FROM AUTHOR]

Crafting single‐atom catalysts (SACs) that possess "just right" modulated electronic and geometric structures, granting accessible active sites for direct room‐temperature benzene oxidation is a coveted objective. However, achieving this goal remains a formidable challenge. Here, we introduce an innovative in situ phosphorus‐immitting strategy using a new phosphorus source (phosphorus nitride, P3N5) to construct the phosphorus‐rich copper (Cu) SACs, designated as Cu/NPC. These catalysts feature locally protruding metal sites on a nitrogen (N)‐phosphorus (P)‐carbon (C) support (NPC). Rigorous analyses, including X‐ray absorption spectroscopy (XAS) and X‐ray photoelectron spectroscopy (XPS), validate the coordinated bonding of nitrogen and phosphorus with atomically dispersed Cu sites on NPC. Crucially, systematic first‐principles calculations, coupled with the climbing image nudged‐elastic‐band (CI‐NEB) method, provide a comprehensive understanding of the structure‐property‐activity relationship of the distorted Cu−N2P2 centers in Cu/NPC for selective oxidation of benzene to phenol production. Interestingly, Cu/NPC has shown more energetically favorable C−H bond activation compared to the benchmark Cu/NC SACs in the direct oxidation of benzene, resulting in outstanding benzene conversion (50.3 %) and phenol selectivity (99.3 %) at room temperature. Furthermore, Cu/NPC achieves a remarkable turnover frequency of 263 h−1 and mass‐specific activity of 35.2 mmol g−1 h−1, surpassing the state‐of‐the‐art benzene‐to‐phenol conversion catalysts to date. [ABSTRACT FROM AUTHOR]

Crafting single‐atom catalysts (SACs) that possess "just right" modulated electronic and geometric structures, granting accessible active sites for direct room‐temperature benzene oxidation is a coveted objective. However, achieving this goal remains a formidable challenge. Here, we introduce an innovative in situ phosphorus‐immitting strategy using a new phosphorus source (phosphorus nitride, P3N5) to construct the phosphorus‐rich copper (Cu) SACs, designated as Cu/NPC. These catalysts feature locally protruding metal sites on a nitrogen (N)‐phosphorus (P)‐carbon (C) support (NPC). Rigorous analyses, including X‐ray absorption spectroscopy (XAS) and X‐ray photoelectron spectroscopy (XPS), validate the coordinated bonding of nitrogen and phosphorus with atomically dispersed Cu sites on NPC. Crucially, systematic first‐principles calculations, coupled with the climbing image nudged‐elastic‐band (CI‐NEB) method, provide a comprehensive understanding of the structure‐property‐activity relationship of the distorted Cu−N2P2 centers in Cu/NPC for selective oxidation of benzene to phenol production. Interestingly, Cu/NPC has shown more energetically favorable C−H bond activation compared to the benchmark Cu/NC SACs in the direct oxidation of benzene, resulting in outstanding benzene conversion (50.3 %) and phenol selectivity (99.3 %) at room temperature. Furthermore, Cu/NPC achieves a remarkable turnover frequency of 263 h−1 and mass‐specific activity of 35.2 mmol g−1 h−1, surpassing the state‐of‐the‐art benzene‐to‐phenol conversion catalysts to date. [ABSTRACT FROM AUTHOR]

Manganese (Mn) oxides are promising cathode materials for rechargeable aqueous Zn‐ion batteries. However, the Mn dissolution in weakly acidic electrolytes always hinders the development of better aqueous Zn–Mn batteries. Herein, a hydroxylated manganese oxide cathode material (H‐MnO2) is fabricated using an electrochemical method for stable aqueous Zn–Mn batteries without relying on the Mn2+ electrolyte additives. The partial hydroxylation of the oxides leads to charge redistribution of the material, changing the reaction thermodynamics and kinetics. Theoretical simulation suggests that the hydroxylation of manganese oxide promotes both Zn2+ adsorption thermodynamics and diffusion kinetics on the surface of H‐MnO2 but weakens the interaction between H+ and the electrode. Therefore, Zn2+ ions can be more reactive with the hydroxylated manganese oxide than H+ ions. Experimental results show that the Zn2+ insertion mechanism dominates the charge storage process of H‐MnO2, and the H+‐induced Mn dissolution reaction is effectively alleviated. Importantly, H‐MnO2 exhibits good cycling stability with 95% capacity retention over 5000 cycles at the current density of 3.8 A g−1 in the ZnSO4 electrolyte, outperforming the state‐of‐the‐art aqueous Zn–Mn batteries, even those with Mn2+ electrolyte additives. The findings provide new insights for designing stable manganese oxide cathodes in aqueous Zn–Mn batteries. [ABSTRACT FROM AUTHOR]

Comprehensive Summary The development of catalytic asymmetric methods that enable access to value‐added functionalities or structures, exemplified by allylic alcohols, is a highly interesting yet challenging topic from both academic and industrial perspectives. However, before recent advances in chemical catalysis, there were scarce protocols toward constructing enantioenriched tertiary allylic alcohol scaffolds. In this context, peptide‐mimic phosphonium salts were found to be highly efficient in catalytic asymmetric α‐hydroxylation of α,β‐unsaturated and/or β,ϒ‐unsaturated compounds with satisfactory regio‐ and stereochemical outcomes (up to 97% yield and 95% ee). This methodology tolerates a broad array of substrates and thus provides an expeditious and unified platform for the assembly of enantioenriched tertiary allylic alcohols by avoiding the use of additional reductants and expensive metal catalysts. Furthermore, the power of this protocol is enlarged by simple conditions and the use of air as a source of hydroxyl functionality. [ABSTRACT FROM AUTHOR]

Selective, one‐step C−H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high‐value hydroxy acids, but to date enzyme discovery has relied on laborious screening and produced limited hits, which predominantly oxidise the subterminal positions of fatty acids. Herein we show that ancestral sequence reconstruction (ASR) is an effective tool to explore the sequence‐activity landscape of a family of multidomain, self‐sufficient P450 monooxygenases. We resurrected 11 catalytically active CYP116B ancestors, each with a unique regioselectivity fingerprint that varied from subterminal in the older ancestors to mid‐chain in the lineage leading to the extant, P450‐TT. In lineages leading to extant enzymes in thermophiles, thermostability increased from ancestral to extant forms, as expected if thermophily had arisen de novo. Our studies show that ASR can be applied to multidomain enzymes to develop active, self‐sufficient monooxygenases as regioselective biocatalysts for fatty acid hydroxylation. [ABSTRACT FROM AUTHOR]

Selective, one‐step C−H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high‐value hydroxy acids, but to date enzyme discovery has relied on laborious screening and produced limited hits, which predominantly oxidise the subterminal positions of fatty acids. Herein we show that ancestral sequence reconstruction (ASR) is an effective tool to explore the sequence‐activity landscape of a family of multidomain, self‐sufficient P450 monooxygenases. We resurrected 11 catalytically active CYP116B ancestors, each with a unique regioselectivity fingerprint that varied from subterminal in the older ancestors to mid‐chain in the lineage leading to the extant, P450‐TT. In lineages leading to extant enzymes in thermophiles, thermostability increased from ancestral to extant forms, as expected if thermophily had arisen de novo. Our studies show that ASR can be applied to multidomain enzymes to develop active, self‐sufficient monooxygenases as regioselective biocatalysts for fatty acid hydroxylation. [ABSTRACT FROM AUTHOR]

Ga2O3 is an ultra‐wide‐bandgap semiconductor that is receiving considerable attention due to its promising applications in high‐frequency, high‐power and high‐temperature settings. It can be prepared by calcinating the α‐GaOOH phase at high temperatures. Understanding the significance of hydroxyl groups in α‐GaOOH, dehydroxylation and the structural transition at high temperatures has become a key aspect of preparing high‐quality α‐Ga2O3 crystals, but the underlying mechanism remains unknown. In this research, α‐GaOOH nanorods were hydrothermally synthesized and the structural evolution of α‐GaOOH investigated at high temperatures by in situ X‐ray diffraction. The hydroxyl group in α‐GaOOH squeezes Ga3+ from the center of the [GaO6] octahedron, resulting in deformed [GaO6] octahedra and significant microstrain in α‐GaOOH. The hydroxyl groups are peeled off from α‐GaOOH when the temperature exceeds 200°C, resulting in contraction along the c‐axis direction and expansion along the a‐axis direction of α‐GaOOH. When the temperature exceeds 300°C, the Ga—O bond inside the double chains preferentially breaks to generate square‐wave‐like octahedron chains, and the neighboring chains repack to form hexagonal‐like octahedron layers. The octahedron layers are packed up and down by electrostatic interaction to generate the α‐Ga2O3 structure. This work highlights the role of hydroxyl groups in α‐GaOOH, dehydroxylation and the structural transition on the atomic scale, providing valuable guidelines for the fabrication of high‐quality α‐Ga2O3 crystals. [ABSTRACT FROM AUTHOR]

A facile solvent casting technique has been reported in the fabrication of surface hydroxylated ZnFe2O4 (h‐ZFO) nanoparticles (NPs) filled with poly(vinylidene fluoride) (PVDF) as a matrix. The h‐ZFO filler particles are synthesized from neat ZnFe2O4. The dielectric and electric performance of polymer‐based composites is much related to the interface binding between filler particles and polymer matrix. In this work, the surface alternation technique employed a new path is developed to improve the compatibility between ZFO particles and the PVDF matrix. These PVDF‐ZFO composites were studied by X‐ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The h‐ZFO‐PVDF and ZFO‐PVDF composites are carefully analyzed by dielectric and electric properties by a wide range of frequencies. However, the morphological analysis exhibits uniform dispersion of the h‐ZFO NPs in the PVDF matrix. The h‐ZFO‐PVDF composites have a dielectric constant of about 35 for 1.5 wt.% of filler contents. Moreover, the h‐ZFO‐PVDF composites have lower dielectric loss than PVDF‐ZFO composites. It is suggested that the strong interaction between h‐ZFO filler particles and the PVDF matrix is the main reason for the improvement of dielectric properties. The outcomes of these methods have great potential for making high dielectric constants and relatively suppressed loss PVDF‐ZFO composites for advanced practical applications. [ABSTRACT FROM AUTHOR]

Aim: Bile acids are suggested to be involved in the antidiarrhetic effect of Goreisan (GRS). This study aimed to investigate the effect of GRS on fecal bile acid levels and composition of the gut microbiota in mice. Correlation analysis was employed to identify the potential gut microbiota associated with the alterations in fecal bile acid levels induced by GRS. Methods: Male C57BL/6 mice were fed a diet supplemented with GRS water extract for 4 weeks. Feces and cecal contents were collected from the mice to determine bile acid levels and analyze bacterial composition. Results: GRS administration significantly increased the levels of fecal secondary bile acids, including ω‐muricholic acid (MCA), hyodeoxycholic acid (HDCA), and lithocholic acid (LCA). In contrast, the levels of primary bile acids, such as β‐MCA, cholic acid (CA), and chenodeoxycholic acid (CDCA) showed a marked decrease. Further analysis revealed a positive correlation between the relative abundance of Alloprevotella, Dehalobacterium PAC001221, and Eubacterium g23 and fecal levels of ωMCA, HDCA, and LCA. Conclusions: GRS was suggested to promote the formation of fecal secondary bile acids in mice, possibly through the enhancement of bacterial 7β‐dehydroxylation and 6β‐epimerization activities. These changes may be involved in the antidiarrhetic action of GRS. Concurrent evaluation of fecal bile acids and gut microbiota presents a promising approach for elucidating the novel mechanisms underlying the effects of kampo formulations, particularly in modulating the microbial metabolism of intestinal bile acids. [ABSTRACT FROM AUTHOR]

Saxitoxin (STX, 1) is a representative compound of paralytic shellfish toxins (PSTs) that are produced by marine dinoflagellates and freshwater cyanobacteria. Although several pathways have been proposed for the biosynthesis of STX, the order of ring and side chain hydroxylation, and formation of the tricyclic skeleton have not been well established. In this study, 12,12‐dideoxy‐decarbamoyloxySTX (dd‐doSTX, 2), the most reduced STX analogue having the tricyclic skeleton, and its analogues, 12β‐deoxy‐doSTX (12β‐d‐doSTX, 3), 12α‐deoxy‐doSTX (12α‐d‐doSTX, 4), and doSTX (5), were synthesized, and these compounds were screened in the toxic microalgae using high‐resolution LCMSMS. dd‐doSTX (2) and 12β‐d‐doSTX (3) were identified in the PSTs‐producing dinoflagellates (Alexandrium catenella, A. pacificum, and/or Gymnodinium catenatum) and in the cyanobacterium Dolichospermum circinale (TA04). doSTX (5), previously isolated from the dinoflagellate G. catenatum, was also identified in D. circinale (TA04). Furthermore, the conversion of 2 to 3, and 4 to 5, by SxtT with VanB, a reported Rieske oxygenase and its redox partner in STX biosynthesis, was confirmed. These results support that 2 is a possible biosynthetic precursor of STX, and that ring and side‐chain hydroxylations proceed after cyclization. [ABSTRACT FROM AUTHOR]

Biocatalytic oxidations are an emerging technology for selective C−H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non‐heme iron and α‐ketoglutarate‐dependent dioxygenase for the direct stereo‐ and regio‐selective hydroxylation of a non‐native fluoroindanone en route to the oncology treatment belzutifan, replacing a five‐step chemical synthesis with a direct enantioselective hydroxylation. Mechanistic studies indicated that formation of the desired product was limited by enzyme stability and product overoxidation, with these properties subsequently improved by directed evolution, yielding a biocatalyst capable of >15,000 total turnovers. Highlighting the industrial utility of this biocatalyst, the high‐yielding, green, and efficient oxidation was demonstrated at kilogram scale for the synthesis of belzutifan. [ABSTRACT FROM AUTHOR]

Biocatalytic oxidations are an emerging technology for selective C−H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non‐heme iron and α‐ketoglutarate‐dependent dioxygenase for the direct stereo‐ and regio‐selective hydroxylation of a non‐native fluoroindanone en route to the oncology treatment belzutifan, replacing a five‐step chemical synthesis with a direct enantioselective hydroxylation. Mechanistic studies indicated that formation of the desired product was limited by enzyme stability and product overoxidation, with these properties subsequently improved by directed evolution, yielding a biocatalyst capable of >15,000 total turnovers. Highlighting the industrial utility of this biocatalyst, the high‐yielding, green, and efficient oxidation was demonstrated at kilogram scale for the synthesis of belzutifan. [ABSTRACT FROM AUTHOR]

Inspired by the ubiquitous prevalence of 3‐hydroxyoxindoles in natural products and pharmaceuticals, we herein disclose a direct and practical transition‐metal‐free asymmetric hydroxylation using commercially available Davis enantiopure oxaziridines as efficient oxidants, expeditiously affording an array of medicinally active 3‐functionalized 3‐hydroxy‐2‐oxindoles bearing quaternary stereocenters. The protocol features cheap reactants, ease of operation, scalability, and good functional‐group tolerance and efficient formal synthesis of natural products. [ABSTRACT FROM AUTHOR]

The Von Hippel–Lindau (VHL) protein, which is frequently mutated in clear-cell renal cell carcinoma (ccRCC), is a master regulator of hypoxia-inducible factor (HIF) that is involved in oxidative stresses. However, whether VHL possesses HIF-independent tumor-suppressing activity remains largely unclear. Here, we demonstrate that VHL suppresses nutrient stress-induced autophagy, and its deficiency in sporadic ccRCC specimens is linked to substantially elevated levels of autophagy and correlates with poorer patient prognosis. Mechanistically, VHL directly binds to the autophagy regulator Beclin1, after its PHD1-mediated hydroxylation on Pro54. This binding inhibits the association of Beclin1-VPS34 complexes with ATG14L, thereby inhibiting autophagy initiation in response to nutrient deficiency. Expression of non-hydroxylatable Beclin1 P54A abrogates VHL-mediated autophagy inhibition and significantly reduces the tumor-suppressing effect of VHL. In addition, Beclin1 P54-OH levels are inversely correlated with autophagy levels in wild-type VHL-expressing human ccRCC specimens, and with poor patient prognosis. Furthermore, combined treatment of VHL-deficient mouse tumors with autophagy inhibitors and HIF2α inhibitors suppresses tumor growth. These findings reveal an unexpected mechanism by which VHL suppresses tumor growth, and suggest a potential treatment for ccRCC through combined inhibition of both autophagy and HIF2α. Synopsis: PHD1-mediated prolyl hydroxylation targets HIF-1α for VHL-dependent ubiquitination and is a key step in the cell's oxygen sensing machinery. This work shows that PHD1 and VHL also inhibit Beclin1 and autophagy initiation, with dysregulation leading to clear-cell renal cell carcinoma progression. PHD1 mediates Beclin1 Pro54 hydroxylation on pre-autophagosomal structures in clear-cell renal cell carcinoma cells. VHL binds to Pro54-hydroxylated Beclin1 and prevents the association between ATG14L and Beclin1/VPS34. VHL inhibits VPS34-dependent PI(3)P production, autophagy initiation, and kidney tumor growth. The Von Hippel-Lindau (VHL) E3 ligase binds to proline-hydroxylated Beclin1, inhibiting the initiation of autophagy and blocking kidney tumor growth. [ABSTRACT FROM AUTHOR]

SznF, a member of the emerging family of heme‐oxygenase‐like (HO‐like) di‐iron oxidases and oxygenases, employs two distinct domains to catalyze the conversion of Nω‐methyl‐L‐arginine (L‐NMA) into N‐nitroso‐containing product, which can subsequently be transformed into streptozotocin. Using unrestricted density functional theory (UDFT) with the hybrid functional B3LYP, we have mechanistically investigated the two sequential hydroxylations of L‐NMA catalyzed by SznF's binuclear iron central domain. Mechanism B primarily involves the O−O bond dissociation, forming Fe(IV)=O, induced by the H+/e− introduction to the FeA side of μ‐1,2‐peroxo‐Fe2(III/III), the substrate hydrogen abstraction by Fe(IV)=O, and the hydroxyl rebound to the substrate N radical. The stochastic addition of H+/e− to the FeB side (mechanism C) can transition to mechanism B, thereby preventing enzyme deactivation. Two other competing mechanisms, involving the direct O−O bond dissociation (mechanism A) and the addition of H2O as a co‐substrate (mechanism D), have been ruled out. [ABSTRACT FROM AUTHOR]

The Cu−O−Cu core has been proposed as a potential site for methane oxidation in particulate methane monooxygenase. In this work, we used density functional theory (DFT) to design a mixed‐valent CuIII−O−CuII species from an experimentally known peroxo‐dicopper complex supported by N‐donor ligands containing phenolic groups. We found that the transfer of two‐protons and two‐electrons from phenolic groups to peroxo‐dicopper core takes place, which results to the formation of a bis‐μ‐hydroxo‐dicopper core. The bis‐μ‐hydroxo‐dicopper core converts to a mixed‐valent CuIII−O−CuII core with the removal of a water molecule. The orbital and spin density analyses unravel the mixed‐valent nature of CuIII−O−CuII. We further investigated the reactivity of this mixed‐valent core for aliphatic C−H hydroxylation. Our study unveiled that mixed‐valent CuIII−O−CuII core follows a hydrogen atom transfer mechanism for C−H activation. An in‐situ generated water molecule plays an important role in C−H hydroxylation by acting as a proton transfer bridge between carbon and oxygen. Furthermore, to assess the relevance of a mixed‐valent CuIII−O−CuII core, we investigated aliphatic C−H activation by a symmetrical CuII−O−CuII core. DFT results show that the mixed‐valent CuIII−O−CuII core is more reactive toward the C−H bond than the symmetrical CuII−O−CuII core. [ABSTRACT FROM AUTHOR]

The purpose of this article is to provide a study of the hydroxylation reaction optimization of epoxidized soybean oil using a mathematical model based on surface response methodology. The variables were selected based on previous studies of the reaction. The three most influential factors are the time, the methanol ratio, and the catalyst ratio. Potentiometric characterization of the hydroxyl index allowed the influence of these factors and their interactions to be measured. It was possible to quantify these influences using multivariate regression. The results show that the three selected factors influenced the reaction yield positively; however, there were some interactions, such as an interaction between time and methanol and the interaction between time and catalyst, which had a negligible influence. The coefficients of the formulas used to construct the mathematical model were obtained from the influence values. The model was able to predict the optimum variable levels for an acceptable reaction yield efficiently and accurately. These levels were: time 244.4 min; methanol:oil ratio 1:4, and catalyst percentage 15.34%. The characterization of the hydroxylated oil product was carried out using Fourier‐transform infrared (FTIR) spectroscopy proton nuclear magnetic resonance (1H‐NMR) and carbon‐13 nuclear magnetic resonance (13C‐NMR) spectroscopy. [ABSTRACT FROM AUTHOR]

In this work, the synthesis and characterization of a heterogeneous photocatalyst based on spherical silica nanoparticles superficially modified with anthraquinone 2‐carboxylic acid (AQ−COOH) are presented. The nanomaterial was characterized by TEM, SEM, FT‐IR, diffuse reflectance, fluorescence, NMR, DLS, XRD and XPS. These analyses confirm the covalent linking of AQ−COOH with the NH2 functionality in the nanomaterial and, more importantly, the photocatalyst retains its photophysical properties once bound. The heterogeneous photocatalyst was successfully employed in the aerobic hydroxylation of arylboronic acids to phenols under sustainable reaction conditions. Phenols were obtained in high yields (up to 100 %) with low catalyst loading (3.5 mol %), reaching TOF values of 3.7 h−1. Using 2‐propanol as solvent at room temperature, the visible light photocatalysis produced H2O2 as a key intermediate to promote the aerobic hydroxylation of arylboronic acids. The heterogeneous photocatalyst was reused at least 5 times, without modification of the nanomaterial structure and morphology. This simple heterogeneous system showed great catalytic activity under sustainable reaction conditions. [ABSTRACT FROM AUTHOR]

Site‐selective C(sp3)−H functionalization of unreactive hydrocarbons is always challenging due to its inherited chemical inertness, slightly different reactivity of various C−H bonds, and intrinsically high bond dissociation energies. Here, a site‐selective C−H alkylation of naphthoquinone with unactivated hydrocarbons using Mn2(CO)10 as a catalyst under blue‐light (457 nm) irradiation without any external acid or base and pre‐functionalization is presented. The selective C−H functionalization of tertiary over secondary and secondary over primary C(sp3)−H bonds in abundant chemical feedstocks was achieved, and hydroxylation of quinones was realized in situ by employing the developed methodology. This protocol provides a new catalytic system for the direct construction of high‐value‐added compounds, namely, parvaquone (a commercially available drug used to treat theileriosis) and its derivatives under ambient reaction conditions. Moreover, this operationally simple protocol applies to various linear‐, branched‐, and cyclo‐alkanes with high degrees of site selectivity under blue‐light irradiated conditions and could provide rapid and straightforward access to versatile methodologies for upgrading feedstock chemicals. Mechanistic insight by radical trapping, radical scavenging, EPR, and other controlled experiments well corroborated with DFT studies suggest that the reaction proceeds by a radical pathway. [ABSTRACT FROM AUTHOR]

Herein, we present a method for electrochemical‐induced 1,3‐oxohydroxylation of arylcyclopropanes with H2O as the green oxygen source. This transformation offers a regioselective route to highly functionalized β‐hydroxy ketones under oxidant‐ and metal‐free conditions. Notably, this electrochemical approach features simple operation, good regioselectivity, high functional group tolerance, and easy derivatization of the products. Mechanistic studies have provided solid evidences that 1,3‐diol acts as the crucial intermediate in this reaction, leading to the observed regioselectivity. [ABSTRACT FROM AUTHOR]

Owing to their high reactivity and selectivity, variations in the spin ground state and a range of possible pathways, high‐valent FeIV=O species are popular models with potential bioinspired applications. An interesting example of a structure–reactivity pattern is the detailed study with five nonheme amine‐pyridine pentadentate ligand FeIV=O species, including N4py: [(L1)FeIV=O]2+ (1), bntpen: [(L2)FeIV=O]2+ (2), py2tacn: [(L3)FeIV=O]2+ (3), and two isomeric bispidine derivatives: [(L4)FeIV=O]2+ (4) and [(L5)FeIV=O]2+ (5). In this set, the order of increasing reactivity in the hydroxylation of cyclohexane differs from that with cyclohexadiene as substrate. A comprehensive DFT, ab initio CASSCF/NEVPT2 and DLPNO‐CCSD(T) study is presented to untangle the observed patterns. These are well reproduced when both activation barriers for the C−H abstraction and the OH rebound are taken into account. An MO, NBO and deformation energy analysis reveals the importance of π(pyr) → π*xz(FeIII‐OH) electron donation for weakening the FeIII‐OH bond and thus reducing the rebound barrier. This requires that pyridine rings are oriented perpendicularly to the FeIII‐OH bond and this is a subtle but crucial point in ligand design for non‐heme iron alkane hydroxylation. [ABSTRACT FROM AUTHOR]

Here we show that the sp‐hybridized nitrogen cation is strongly stabilized by a peri‐iodine substituent in the tetralone system. The cation is captured by anionic species such as CF3CO2−, affording hypervalent iodine(III) compounds with a short nitrogen‐iodine (N−I) bond, in which the cation serves as a Lewis acid. Notably, the O−I bond of the O‐trifluoroacetate or O‐acetate is intrinsically weaker than the N−I bond due to its more ionic character and is further weakened by protonation in trifluoroacetic acid. As a result, the oxygen ligand can dissociate in the presence of a Brønsted acid, affording a I+ cation intermediate that retains the N−I bond. We isolated the cation as the tetrafluoroborate, and characterized it experimentally by 1H NMR spectroscopy and X‐ray structure analysis, and theoretically by means of DFT calculation. The results suggest that the N−I bonded cation is intrinsically stable, and is weakly coordinated with water and the BF4 counter anion or trifluoroacetate anion. This cation can be employed as a reagent for α‐oxidation of ketones. [ABSTRACT FROM AUTHOR]

A combination of reagents using I2 and DMSO has been established for the selective transformation of unactivated alkenes into iodohydrins and β‐iodoethers. The developed approach was served by the dual roles of DMSO as an oxidant as well as a hydroxylating agent under different solvent systems at 85 °C. The developed method holds an operational simplicity and is consistent with wide range of substituted alkenes to deliver iodohydrins and β‐iodoethers in yields up to 86 %. The formation of iodohydrins are selective in MeCN as solvent and the course of the reaction was examined by GC‐MS studies and DFT method. [ABSTRACT FROM AUTHOR]

Herein we report a structure‐unit‐based asymmetric total synthesis of sinulochmodin C, a norcembranoid diterpenoid bearing a transannular strained ether bridge β‐keto tetrahydrofuran moiety. Our synthetic route features an intramolecular double Michael addition to construct stereospecifically the [7,6,5,5] tetracyclic skeleton, a vinylogous hydroxylation/oxidation procedure or a stereospecific epoxide opening/oxidation sequence to establish the γ‐keto enone intermediate, a Lewis acid/Brønsted acid mediated transannular oxa‐Michael addition to fuse the β‐keto tetrahydrofuran moiety, a Mukaiyama hydration/Pd−C hydrogenation to reverse the C1‐configuration of the isopropenyl unit, and a bioinspired transformation of sinulochmodin C into scabrolide A. [ABSTRACT FROM AUTHOR]

As a crucial class of functional molecules in organosilicon chemistry, silanols are found valuable applications in the fields of modern science and will be a potentially powerful framework for biologically active compounds or functional materials. It has witnessed an increasing demand for non‐natural organosilanols, as well as the progress in the synthesis of these structural features. From the classic preparative methods to the catalytic selective oxidation of hydrosilanes, electrochemical hydrolysis of hydrosilanes, and then the construction of the most challenging silicon‐stereogenic silanols. This review summarized the progress in the catalyzed synthesis of silanols via hydroxylation of hydrosilanes in the last decade, with a particular emphasis on the latest elegant developments in the desymmetrization strategy for the enantioselective synthesis of silicon‐stereogenic silanols from dihydrosilanes. [ABSTRACT FROM AUTHOR]

Herein we report a structure‐unit‐based asymmetric total synthesis of sinulochmodin C, a norcembranoid diterpenoid bearing a transannular strained ether bridge β‐keto tetrahydrofuran moiety. Our synthetic route features an intramolecular double Michael addition to construct stereospecifically the [7,6,5,5] tetracyclic skeleton, a vinylogous hydroxylation/oxidation procedure or a stereospecific epoxide opening/oxidation sequence to establish the γ‐keto enone intermediate, a Lewis acid/Brønsted acid mediated transannular oxa‐Michael addition to fuse the β‐keto tetrahydrofuran moiety, a Mukaiyama hydration/Pd−C hydrogenation to reverse the C1‐configuration of the isopropenyl unit, and a bioinspired transformation of sinulochmodin C into scabrolide A. [ABSTRACT FROM AUTHOR]

Electronic components made by inorganics (e.g., mica) play key roles in the function exertion of instruments working in outer‐layer space, enduring long‐term β‐ray irradiation. Its damage is vital while explored rarely. Herein, pure muscovite crystals were chosen and irradiated by an electron beam (EB) in air with a dose up to 1000 kGy. Then, micro‐geometry morphology variation in Z‐axis and microstructural transformation mechanism were explored by X‐ray diffraction, Fourier transform attenuated total reflection infrared spectrum, thermogravimetric analysis, X‐ray photoelectron spectroscopy, and CA analysis. Main results reveal that muscovite lattice is unstable to EB irradiation. With dose increases to 1000 kGy, interlayer space d of (0 0 2) lattice varied 2% near 0.2 Å. At low‐dose, irradiation lattice expansion readily occurs, whereas at higher dose, it is lattice shrinkage, showing a transformation from expansion to shrinkage. Concurrently, chemical structure varied, H2O amount increased, and metal element valance and surface wettability were reduced, so dehydroxylation occurred exceeding H2O radiolysis and evaporation, and framework cleavage could be severe. Binding energies of metals of 1000 kGy‐irradiated species decreased by 0.2 eV, and CA of 100 kGy‐irradiated species increased by 10°. Intrinsic mechanisms involve framework destruction, H‐atom migration, hydrogen bond formation/destruction, and H2O radiolysis. At low‐dose irradiation, H‐atom migration and hydrogen bond formation/destruction are predominant, inducing lattice expansion; at higher dose, framework cleavage is intensive and crucial, inducing shrinkage. During which, partial H2O occurred radiolysis, reducing valence. Generally, H‐atom migration and interface cleavage played key roles in microgeometry morphology a variation of muscovite crystal under EB irradiation at 0–1000 kGy. To enhance muscovite geometry‐morphology stability under a long‐term β‐ray irradiation condition, OH and hydrogen bond contents should be reduced and interface region should be strengthened (e.g., lessening vacancies or compacting stacking). This conclusion promotes the design of radiation‐resistant silicate material, guiding the manufacturing of electronic component used in aerospace industry significantly. [ABSTRACT FROM AUTHOR]

Steroid hydroxylations belong to the industrially most relevant reactions catalysed by cytochrome P450 monooxygenases (CYP450s) due to the pharmacological relevance of hydroxylated derivatives. The implementation of respective bioprocesses at an industrial scale still suffers from several limitations commonly found in CYP450 catalysis, that is low turnover rates, enzyme instability, inhibition and toxicity related to the substrate(s) and/or product(s). Recently, we achieved a new level of steroid hydroxylation rates by introducing highly active testosterone‐hydroxylating CYP450 BM3 variants together with the hydrophobic outer membrane protein AlkL into Escherichia coli‐based whole‐cell biocatalysts. However, the activity tended to decrease, which possibly impedes overall productivities and final product titres. In this study, a considerable instability was confirmed and subject to a systematic investigation regarding possible causes. In‐depth evaluation of whole‐cell biocatalyst kinetics and stability revealed a limitation in substrate availability due to poor testosterone solubility as well as inhibition by the main product 15β‐hydroxytestosterone. Instability of CYP450 BM3 variants was disclosed as another critical factor, which is of general significance for CYP450‐based biocatalysis. Presented results reveal biocatalyst, reaction and process engineering strategies auguring well for industrial implementation of the developed steroid hydroxylation platform. [ABSTRACT FROM AUTHOR]

Conducting electrochemical organic synthesis in/on whole water media is undoubtedly a highly green approach, which avoids the usage of organic solvents, and sometimes organic supporting electrolytes. In this review, the electrochemical organic syntheses in/on whole water environment are reviewed, especially including the reactions conducted both in organic solvent and water for comparisons. This review discussed anodic and cathodic reaction, respectively, including the C−H oxidation, hydroxylation, dehydrogenative cross coupling, functionalization of alkenes, cathodic oxidation, hydrogenation, reductive cross coupling, and so on. As the reduction of CO2, conversion biomass, and waste water disposal are frequently performed in water, and have already been reviewed recently. These topics are not included in this review. [ABSTRACT FROM AUTHOR]

An ionic liquid, namely imidazolium sulfonic acid chloride (ISAC) has been electrostatically grafted over cerium oxide nanoparticles to produce a nanocomposite, nano‐CeO2‐IL. The as‐prepared composite was characterized by various analytical techniques such as XRD, FT‐IR, SEM, TEM, XPS, BET, UV‐DRS, PL, and TGA to confirm the grafting of ISAC over CeO2 NPs. The photocatalytic process is regarded as the method of choice for the elimination of air pollutants because of its great efficiency and relatively benign working conditions. According to UV‐DRS spectra, its optical gap is 2.07 eV, which is appropriate for the visible light spectrum. The composite was investigated as a visible‐light‐driven photocatalyst for hydroxylation of benzene to phenol and heavy metal Cr (VI) reduction. Moreover, the scavenger experiments confirmed the detection of ⋅OH radicals which played a crucial role in the photocatalytic experiments. Within 60 minutes, 98.5 % of benzene was converted to phenol with 82.7 % selectivity in addition to 93.63 % Cr (VI) reduction within 30 mins. The photocatalytic reduction of Cr(VI) to Cr(III) follows a first‐order model with a rate constant of 0.027 min−1. The remarkably high photocatalytic performance of the catalyst may be ascribed to the synergistic interaction between the nano‐CeO2 catalyst and ionic liquid. [ABSTRACT FROM AUTHOR]

The electron transfer (ET) step is one of the crucial processes in biochemical redox reactions that occur in nature and has been established as a key step in dictating the reactivity of high‐valent metal‐oxo species. Although metalloenzymes possessing metal‐oxo units at their active site are typically associated with outer‐sphere electron transfer (OSET) processes, biomimetic models, in contrast, have been found to manifest either an inner‐sphere electron transfer (ISET) or OSET mechanism. This distinction is clearly illustrated through the behaviour of [(N4Py)MnIV(O)]2+ (1) and [(N4Py)FeIV(O)]2+ (2) complexes, where complex 1 showcases an OSET mechanism, while complex 2 exhibits an ISET mechanism, especially evident in their reactions involving C−H bond activation and oxygen atom transfer reactions in the presence of a Lewis/Bronsted acid. However, the precise reason for this puzzling difference remains elusive. This work unveils the origin of the perplexing inner‐sphere vs outer‐sphere electron transfer process (ISET vs OSET) in [(N4Py)MnIV(O)]2+ (1) and [(N4Py)FeIV(O)]2+ (2) species in the presence of Bronsted acid. The calculations indicate that when the substrate (toluene) approaches both 1 and 2 that is hydrogen bonded with two HOTf molecules (denoted as 1‐HOTf and 2‐HOTf, respectively), proton transfer from one of the HOTf molecules to the metal‐oxo unit is triggered and a simultaneous electron transfer occurs from toluene to the metal centre. Interestingly, the preference for OSET by 1‐HOTf is found to originate from the choice of MnIV=O centre to abstract spin‐down (β) electron from toluene to its δ(dxy) orbital. On the other hand, in 2‐HOTf, a spin state inversion from triplet to quintet state takes place during the proton (from HOTf) coupled electron transfer (from toluene) preferring a spin‐up (α) electron abstraction to its σ*(dz2) orbital mediated by HOTf giving rise to ISET. In addition, 2‐HOTf was calculated to possess a larger reorganisation energy, which facilitates the ISET process via the acid. The absence of spin‐inversion and smaller reorganisation energy switch the mechanism to OSET for 1‐HOTf. Therefore, for the first time, the significance of spin‐state and spin‐inversion in the electron transfer process has been identified and demonstrated within the realm of high‐valent metal‐oxo chemistry. This discovery holds implications for the potential involvement of high‐valent Mn‐oxo species in performing similar transformative processes within Photosystem II. [ABSTRACT FROM AUTHOR]

A new, improved 2nd generation route for the synthesis of 3‐ethyl‐4‐hydroxy‐5‐methylbenzonitrile has been developed. The original route started from 2‐ethyl‐6‐methylaniline, which was converted by a classical sequence of para‐bromination, cyanation and Sandmeyer hydroxylation into the desired phenol. This route was used on multi‐kg scale and delivered the product with the desired purity. However, the route was not ideal, as it featured safety critical steps (cyanation), employed undesirable solvents (DMF), included laborious workup and isolation procedures, and suffered from a low overall yield (40–45 %) and suboptimal green metrics (PMI: 210). We envisioned a new, non‐classical approach to the product by introducing the nitrile through a para‐selective formylation, followed by transformation of the intermediate aldehyde into the nitrile with hydroxylamine‐O‐sulfonic acid (HOSA). The new sequence of Sandmeyer hydroxylation, Duff formylation and HOSA‐promoted nitrile formation was thoroughly optimized and finally scaled up to 400 g. This novel 3‐step sequence delivered 3‐ethyl‐4‐hydroxy‐5‐methylbenzonitrile in 69 % overall yield with excellent purity (99.3 % a/a) and a vastly improved PMI of 81. [ABSTRACT FROM AUTHOR]

In recent years, metalloenzymes‐mediated highly selective oxidations of organic substrates under mild conditions have been inspiration for developing synthetic bioinspired catalyst systems, capable of conducting such processes in the laboratory (and, in the future, in industry), relying on easy‐to‐handle and environmentally benign oxidants such as H2O2. To date, non‐heme manganese complexes with chiral bis‐amino‐bis‐pyridylmethyl and structurally related ligands are considered as possessing the highest synthetic potential, having demonstrated the ability to mediate a variety of chemo‐ and stereoselective oxidative transformations, such as epoxidations, C(sp3)‐H hydroxylations and ketonizations, oxidative desymmetrizations, kinetic resolutions, etc. Furthermore, in the past few years non‐heme Mn based catalysts have become the major platform for studies focused on getting insight into the molecular mechanisms of oxidant activation and (stereo)selective oxygen transfer, testing non‐traditional hydroperoxide oxidants, engineering catalytic sites with enzyme‐like substrate recognition‐based selectivity, exploration of catalytic regioselectivity trends in the oxidation of biologically active substrates of natural origin. This contribution summarizes the progress in manganese catalyzed C‐H oxygenative transformations of organic substrates, achieved essentially in the past 5 years (late 2018–2023). [ABSTRACT FROM AUTHOR]

An asymmetric formal synthesis of (+)‐phomactin A has been accomplished. The key steps in the synthetic strategy included establishing the AB ring system in one‐pot via Prins/Conia‐ene cascade cyclization reaction and the C ring formation via γ‐hydroxylation of enone in the late‐stage of the synthesis. The two major fragments are readily prepared from (+)‐pulegone and geraniol via a modified Eschenmoser–Tanabe fragmentation strategy in 6 steps and a Sharpless asymmetric epoxidation/hydrozirconation/ Roskamp reaction sequence in 11 steps respectively. [ABSTRACT FROM AUTHOR]

Identifying (bio)catalysts displaying high enantio‐/stereoselectivity is a fundamental prerequisite for the advancement of asymmetric catalysis. Herein, a high‐throughput, stereoselective screening assay is reported that gives information on enantioselectivity, stereopreference and activity as showcased for peroxygenase‐catalyzed hydroxylation. The assay is based on spectrophotometric analysis of the simultaneous formation of NAD(P)H from the alcohol dehydrogenase catalyzed enantioselective oxidation of the sec‐alcohol product formed in the peroxygenase reaction. The assay was applied to investigate a library comprising 44 unspecific peroxygenases (UPOs) containing 25 UPOs not reported yet. Thereby, previously non‐described wild‐type UPOs displaying (S)‐ as well as (R)‐stereoselectivity for the hydroxylation of representative model substrates were identified, reaching up to 98 % ee for the (R)‐ and 94 % ee for the (S)‐enantiomer. Homology models with concomitant docking studies indicated the structural reason for the observed complementary stereopreference. [ABSTRACT FROM AUTHOR]

Identifying (bio)catalysts displaying high enantio‐/stereoselectivity is a fundamental prerequisite for the advancement of asymmetric catalysis. Herein, a high‐throughput, stereoselective screening assay is reported that gives information on enantioselectivity, stereopreference and activity as showcased for peroxygenase‐catalyzed hydroxylation. The assay is based on spectrophotometric analysis of the simultaneous formation of NAD(P)H from the alcohol dehydrogenase catalyzed enantioselective oxidation of the sec‐alcohol product formed in the peroxygenase reaction. The assay was applied to investigate a library comprising 44 unspecific peroxygenases (UPOs) containing 25 UPOs not reported yet. Thereby, previously non‐described wild‐type UPOs displaying (S)‐ as well as (R)‐stereoselectivity for the hydroxylation of representative model substrates were identified, reaching up to 98 % ee for the (R)‐ and 94 % ee for the (S)‐enantiomer. Homology models with concomitant docking studies indicated the structural reason for the observed complementary stereopreference. [ABSTRACT FROM AUTHOR]

The P450 monooxygenase CYP109A2 from Bacillus megaterium DSM319 was previously found to convert vitamin D3 (VD3) to 25‐hydroxyvitamin D3. Here, we show that this enzyme is also able to convert testosterone in a highly regio‐ and stereoselective manner to 16β‐hydroxytestosterone. To reveal the structural determinants governing the regio‐ and stereoselective steroid hydroxylation reactions catalyzed by CYP109A2, two crystal structures of CYP109A2 were solved in similar closed conformations, one revealing a bound testosterone in the active site pocket, albeit at a nonproductive site away from the heme‐iron. To examine whether the closed crystal structures nevertheless correspond to a reactive conformation of CYP109A2, docking and molecular dynamics (MD) simulations were performed with testosterone and vitamin D3 (VD3) present in the active site. These MD simulations were analyzed for catalytically productive conformations, the relative occurrences of which were in agreement with the experimentally determined stereoselectivities if the predicted stability of each carbon‐hydrogen bond was taken into account. Overall, the first‐time determination and analysis of the catalytically relevant 3D conformation of CYP109A2 will allow for future small molecule ligand screening in silico, as well as enabling site‐directed mutagenesis toward improved enzymatic properties of this enzyme. [ABSTRACT FROM AUTHOR]

The first total synthesis of (−)‐5‐deoxyenterocin has been accomplished starting from pentane‐1,3,5‐triol (16 steps in the longest linear sequence, 0.2 % overall yield). (−)‐Menthone served as the source of chirality to distinguish the enantiotopic hydroxymethyl groups of the substrate. Key steps of the synthesis include two aldol reactions to either end of the C5‐skeleton, a diastereoselective hydroxylation reaction and a biomimetic twofold intramolecular aldol reaction as the final step. Although this step suffered from geometrical constraints and was low yielding (10 %), enough synthetic material could be secured to substantiate the relative and absolute configuration of the natural product. Additional experiments were directed toward a C−H functionalization at carbon atom C5. Despite the fact that several protocols could be successfully applied to (3aR)‐(+)‐sclareolide as model substrate, (−)‐5‐deoxyenterocin withstood any selective functionalization. [ABSTRACT FROM AUTHOR]

Electrochemical oxidation of the new psychoactive substance 3‐fluorophenmetrazine (FPM) was studied in phosphate buffers by cyclic voltammetry and differential pulse voltammetry (DPV) on a glassy carbon electrode. The redox potential of FPM in buffered solution strongly depends on pH. Cyclic voltammetry behavior shows the partial influence of adsorption on the electrode process not allowing detailed analysis of the individual steps of the reaction scheme, it means the involvement of electron transfer (E) and chemical reaction (C). Nevertheless, the irreversible shape of the cyclic voltammogram is explained by the participation of hydroxylation nucleophilic addition of water (hydroxylation) after two‐electron/two‐proton oxidation of molecule at the tetrahydro‐1,4‐oxazine ring. The suggested mechanism leading to hydroxylated derivative 2‐(3‐fluorophenyl)‐3‐methyl‐5‐hydroxymorfolin is supported by the calculated highest occupied molecular orbital spatial distribution and atomic charges calculations for electrochemically formed radical cation. Infrared spectroelectrochemistry performed during oxidation in acetonitrile/water also supported the formation of this product. The analytical method of FPM determination on glassy carbon electrode was developed using DPV with an attained limit of detection = 4.7 μmol/L in phosphate buffer of pH 9. The linear range of the calibration curve is from 7.0 to 107.00 μmol/L, correlation coefficient (r) = 0.9988. [ABSTRACT FROM AUTHOR]

A versatile catalytic platform consisting of pyridine‐containing oxalamide and copper salt was developed. The resulting complexes were fully characterized by spectroscopic analyses, showing a successful complexation of copper metal. The applicability of the newly prepared platforms was evaluated in a one‐pot three‐components system for the preparation of 1,4‐disubstituted 1,2,3‐triazole via 1,3‐dipolar cycloaddition of terminal acetylenes, benzyl surrogates, and sodium azide in an aqueous environment. The corresponding cyclization proceeded smoothly affording the expected triazole products in moderate to good yields. In addition, the transformation of arylboronic acids to the corresponding phenols via ipso‐hydroxylation was also explored using the same platform in an aqueous basic condition. In the course of the study, unfortunately, some drawbacks that could limit the applicability of the catalytic platform were also observed especially in terms of recyclability of the platforms. [ABSTRACT FROM AUTHOR]

A new route to the macrolactone antibiotic berkeleylactone A was developed. As a key step, a ring‐closing alkyne metathesis (RCAM) of an ester substrate featuring 1‐propynyl termini was used. The carboxylic part of the substrate was easily assembled using alkyne chemistry, like carboxylation of a diyne followed by isomerization of the ynoate section to a dienoate and dihydroxylation of the 4,5‐double bond. The synthesis of the alcohol part of the ester started with opening of (R)‐propylene oxide with an acetylide and was followed by two triple bond migrations. After successful RCAM which formed the C8−C9 bond, the triple bond was selectively hydrogenated to the corresponding alkene before the 4,5‐diol was oxidized to the 5‐hydroxy‐4‐oxo derivative. At this stage, the thioether was formed and the 8,9‐double bond reduced. We also prepared the 8,9‐didehydro analog of berkeleylactone A. However, it turned out that its antimicrobial activity was slightly reduced. [ABSTRACT FROM AUTHOR]

We have developed a straightforward methodology for converting arylboronic acids into phenols using NaOH‐mediated air oxidation. This reaction offers several advantages, including simple operation, excellent tolerance towards various functional groups, and scalability. The transmetalation of the resulting borate ester with NaOH occurs readily, enabling convenient derivatization of the borate ester into aryl ethers and esters using alkyl and acyl halides. [ABSTRACT FROM AUTHOR]