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Drug leads with a high Fsp3 index are more likely to possess desirable properties for progression in the drug development pipeline. This paper describes the first detailed NMR analysis of the borylated intermediate 3-deoxy-3-boronodiethanolamine-1,2:5,6-di-O-isopropylidene-α-d-galactofuranose and of the corresponding free monosaccharide analogue 3-boronic-3-deoxy-d-galactose in the early stage of the concurrent equilibrium processes of mutarotation and borarotation. A discussion of all potential equilibria is also presented alongside a comparison with relevant 11B-NMR data available from the scientific literature and our own library. [ABSTRACT FROM AUTHOR]

Complex dynamic systems displaying interdependency between nitroaldol and boronic ester reactions have been demonstrated. Nitroalkane‐1,3‐diols, generated by the nitroaldol reaction, were susceptible to ester formation with different boronic acids in aprotic solvents, whereas hydrolysis of the esters occurred in the presence of water. The boronic ester formation led to significant stabilization of the nitroaldol adducts under basic conditions. The use of bifunctional building blocks was furthermore established, allowing for main chain nitroaldol‐boronate dynamers as well as complex network dynamers with distinct topologies. The shape and rigidity of the resulting dynamers showed an apparent dependency on the configuration of the boronic acids. [ABSTRACT FROM AUTHOR]

Some antibiotics that are frequently employed are β-lactams. In light of the hydrolytic process of β-lactamase, found in Gram-negative bacteria, inhibitors of β-lactamase (BLIs) have been produced. Examples of first-generation β-lactamase inhibitors include sulbactam, clavulanic acid, and tazobactam. Many kinds of bacteria immune to inhibitors have appeared, and none cover all the β-lactamase classes. Various methods have been utilized to develop second-generation β-lactamase inhibitors possessing new structures and facilitate the formation of diazabicyclooctane (DBO), cyclic boronate, metallo-, and dual-nature β-lactamase inhibitors. This review describes numerous promising second-generation β-lactamase inhibitors, including vaborbactam, avibactam, and cyclic boronate serine-β-lactamase inhibitors. Furthermore, it covers developments and methods for synthesizing MβL (metallo-β-lactamase inhibitors), which are clinically effective, as well as the various dual-nature-based inhibitors of β-lactamases that have been developed. Several combinations are still only used in preclinical or clinical research, although only a few are currently used in clinics. This review comprises materials on the research progress of BLIs over the last five years. It highlights the ongoing need to produce new and unique BLIs to counter the appearance of multidrug-resistant bacteria. At present, second-generation BLIs represent an efficient and successful strategy. [ABSTRACT FROM AUTHOR]

gem‐Diborylalkanes are highly valuable building blocks in organic synthesis and pharmaceutical chemistry due to their ability to participate in multi‐step cross‐coupling transformations, allowing for the rapid generation of molecular complexity. While progress has been made in their synthetic metholodology, the construction of β‐tertiary and C(sp3)‐rich gem‐diborylalkanes remains a synthetic challenge due to substrate limitations and steric hindrance issues. An approach is presented that utilizes synergistic photoredox and copper catalysis to achieve efficient C(sp3)−C(sp3) cross‐coupling of alkyl N‐hydroxyphthalimide esters, which can easily be obtained from alkyl carboxylic acids, with diborylmethyl species, providing a series of C(sp3)‐rich gem‐diborylalkanes with 1°, 2°, and even 3° β positions. Furthermore, this approach can also be applied to complex medicinal compounds and natural products, offering rapid access to molecular complexity and late‐stage functionalization of C(sp3)‐rich drug candidates. Mechanistic experiments revealed that diborylmethyl Cu(I) species participated in both the photoredox process and the key C(sp3)−C(sp3) bond‐forming step. [ABSTRACT FROM AUTHOR]

Scalable [3+2] cycloaddition of alkynyl boronates and in situ generated unstabilized azomethine ylide is reported for the first time. The selective formation of either 1 : 1 or 1 : 2 cycloaddition products was achieved by carefully optimizing the reaction conditions, mainly by controlling the reactant stoichiometry, catalyst loading, and internal temperature. The developed protocol tolerated many valuable functional groups, including TMS, protected alcohol (as ether or THP derivatives), or aldehyde (as acetal). Further common C−C and C−heteroatom bond‐forming reactions, as well as scaled‐up procedures demonstrate the utility of the prepared compounds as building blocks for organic synthesis and drug discovery. [ABSTRACT FROM AUTHOR]

[34] The reaction with enantioenriched -methylbenzylboronic acid pinacol ester resulted in a 56:44 diastereomeric mixture of alcohol products B 48 b , the same diastereomeric mixture as was observed using racemic alkylboronic ester. [3][5][6] This short review details our laboratory's examination of reactions using benzylboronic acid pinacol ester and secondary and tertiary benzylboronic esters as nucleophiles. Keywords: boron; benzylation; Lewis base; copper; boronate EN boron benzylation Lewis base copper boronate 2639 2647 9 08/17/23 20230901 NES 230901 Graph 1 Introduction Organoboranes have found great utility in organic synthesis. Specifically, substrates containing esters and amides to the ketone were found to be compatible under these reaction conditions with no reaction being observed at the ester or amide carbonyl carbon ( B 25 b and B 26 b ). [Extracted from the article]

Drug leads with a high Fsp3 index are more likely to possess desirable properties for progression in the drug development pipeline. This paper describes the development of an efficient two-step protocol to completely diastereoselectively access a diethanolamine (DEA) boronate ester derivative of monosaccharide d-galactose from the starting material 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. This intermediate, in turn, is used to access 3-boronic-3deoxy-d-galactose for boron neutron capture therapy (BNCT) applications. The hydroboration/borane trapping protocol was robustly optimized with BH3.THF in 1,4-dioxane, followed by in-situ conversion of the inorganic borane intermediate to the organic boron product by the addition of DEA. This second step occurs instantaneously, with the immediate formation of a white precipitate. This protocol allows expedited and greener access to a new class of BNCT agents with an Fsp3 index = 1 and a desirable toxicity profile. Furthermore, presented is the first detailed NMR analysis of the borylated free monosaccharide target compound during the processes of mutarotation and borarotation. [ABSTRACT FROM AUTHOR]

Low molecular weight organogelators provide useful materials which have already found applications in various fields. Recently, phenylboronate alkylglucosides have become new members of this type of organogelators providing water‐sensitive gels. This work is focused on the impact of the position of alkyl and phenyl moieties within this type of structures. Thus, alkylboronate phenylglucoside and alkylboronate alkylglucoside counterparts were synthesized and studied. Organogels obtained in toluene and ethyl myristate were characterized by rheology and electron microscopy. In addition, we also determined the disruption rates of such organogels upon addition of a small amount of water. Alkylboronate alkylglucosides did not induce gelation of the tested solvents but all derivatives bearing a phenyl ring either on the boronate function or on the glucoside unit came out as good organogelators. However, alkylboronates were found to have higher water sensitivities than phenyl counterparts. Thus, this work has enlarged the scope of glucoside‐boronate organogelators and their water sensitivity which can represent useful materials in drug delivery systems for example. [ABSTRACT FROM AUTHOR]

In this study, privileged boronic acid ester was introduced into the right wing of etravirine (ETR) to obtain a series of novel boronate-containing derivatives. These newly synthesized derivatives were evaluated for their anti-HIV potency in MT-4 cells using the MTT method, and their inhibitory activity to HIV-1 reverse transcriptase (RT) was assayed by the ELISA method. Most of the synthesized compounds displayed promising antiviral activity against the wild-type and a wide range of HIV-1 mutant strains. In particular, 4a exhibited the most potent activity against the wild-type and a panel of single mutations (L100I, K103N, Y181C, and E138K) with EC50 values ranging from 0.005 to 0.648 μM, which were much superior to those of nevirapine (EC50 = 0.151 μM). Moreover, 4b turned out to be an effective inhibitor against the double-mutant strains F227L + V106A and RES056 with EC50 values of 3.21 and 2.30 μM, respectively. RT inhibition activity and molecular docking were also investigated. [ABSTRACT FROM AUTHOR]

A scalable and efficient process for the preparation of 3‐borylated pyrrolidines by 1,3‐dipolar cycloaddition of N‐benzyl azomethine ylide generated in situ has been developed. The optimized method included the use of LiF in DMSO at 110 °C and was suitable for α‐mono‐, α,β‐di‐, and α,β,β‐trialkyl‐, β,β‐(hetera)cycloalkylidene‐, CO2Et‐, as well as most β‐(het)aryl‐substituted alkenyl boropinacolates. The 1,3‐dipolar reaction proceeded on a multigram scale providing 3‐borylated pyrrolidines with diverse substitution patterns (including fused and spirocyclic ones) in a diastereoselective manner. The Pd(OH)2‐mediated N‐debenzylation of pyrrolidine hydrochlorides was successfully performed to give the corresponding bifunctional building blocks on an up to 130 g scale, thus providing a substantial expansion of the synthetic and medicinal chemist's toolbox. Other reactions included the preparation of trifluoroborates, Zweifel‐Aggarwal sp3‐sp2 coupling, and oxidative deborylation as an example of C‐heteroatom bond formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of C/O , C/S and C/C disaccharide analogues of alpha-Gal. • Synthesis of E-C -glycosyl crotylboronates. • TRIP catalyzed stereoselective reactions of C-glycosyl crotylboronates. The synthesis of C-disaccharides of α- d -galactopyranosyl-(1 → 3)- d -galactopyranose (α-Gal), potential tools for studying the biology of α-Gal glycans, is described. The synthetic strategy, centers on the reaction of two easily available precursors 1,2-O-isopropylidene- d -glyceraldehyde and an α-C-glactosyl- E -crotylboronate, which affords a mixture of two diastereomeric anti-crotylation products. The stereoselectivity of this reaction was controlled with (R)- and (S)-TRIP catalysts, and the appropriate diastereomer was transformed to C-linked disaccharides of α-Gal, in which the aglycone segment comprised O-, C- and S-glycoside entities that can enable glycoconjugate synthesis. [ABSTRACT FROM AUTHOR]

Herein, the copper‐catalyzed borylation of readily available acyl chlorides with bis(pinacolato)diboron, (B2pin2) or bis(neopentane glycolato)diboron (B2neop2) is reported, which provides stable potassium acyltrifluoroborates (KATs) in good yields from the acylboronate esters. A variety of functional groups are tolerated under the mild reaction conditions (room temperature) and substrates containing different carbon‐skeletons, such as aryl, heteroaryl and primary, secondary, tertiary alkyl are applicable. Acyl N‐methyliminodiacetic acid (MIDA) boronates can also been accessed by modification of the workup procedures. This process is scalable and also amenable to the late‐stage conversion of carboxylic acid‐containing drugs into their acylboron analogues, which have been challenging to prepare previously. A catalytic mechanism is proposed based on in situ monitoring of the reaction between p‐toluoyl chloride and an NHC‐copper(I) boryl complex as well as the isolation of an unusual lithium acylBpinOBpin compound as a key intermediate. [ABSTRACT FROM AUTHOR]

Abstract Two series of N-methyliminodiacetic acid (MIDA) boronates were prepared and their mesomorphic properties were investigated. MIDA-substituted benzoic acid esters were synthesized via the Mitsunobu reaction. The second series of MIDA benzyl ether derivatives was prepared via Williamson etherification and subsequent borylation. Both series exhibit smectic A (SmA) phases. In the case of MIDA boronate esters, a substitution with perfluorinated side chains led to increased transition temperatures and broadening of the SmA phases. The phase geometries of the mesophases were determined by X-ray diffraction. Quantum-chemical calculations provided further insight into the packing model.

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal‐free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2neop2), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late‐stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates. [ABSTRACT FROM AUTHOR]

Abstract Herein, we report the evaluation and synthesis of a reaction based fluorescent probe DCM‐Bpin for the detection of Peroxynitrite (ONOO−). DCM‐Bpin exhibits selective fluorescence off‐on response for ONOO− over other reactive oxygen species, including H2O2. Moreover, DCM‐Bpin is biocompatible and has been used to visualize exogenous ONOO− in HeLa cells.

[Display omitted] • An enrichment method of glycoproteins using microfluidic paper-based analytical devices (μPADs) was developed. • The μPADs consist of two separate parts: the enrichment part (Chip I) and the detection part (Chip II). • The 3-aminophenylboronic acid immobilized on Chip I can capture glycoproteins at pH 8.0 and release them at pH 3.0. • The method can effectively enrich an ovalbumin solution with concentrations as low as 1.0 × 10−11 mol/L. • Glycoproteins was enriched from 1 × 106-fold diluted real egg white samples. We introduce a facile method for glycoprotein enrichment, separation, and detection using microfluidic paper-based analytical devices (μPADs). The μPADs comprise two distinct components: the enrichment region (Chip I) and the detection section (Chip II). The reusable Chip I is fabricated by immobilizing 3-aminophenylboronic acid (APBA) onto a circular paper substrate, demonstrating exceptional glycoprotein affinity. In disposable Chip II, glycoproteins react with periodic acid, generating carbonyl compounds that produce a purple-colored product upon reacting with the Schiff reagent. Alterations in color intensity are captured using an ordinary cell phone and are subsequently analyzed using Photoshop software. Observations note a linear increase in average color intensities from 1.0 × 10−3 to 5.0 × 10−3 mol/L, with an R2 value of 0.9927. The relative standard deviations (RSDs) of inter-day (n = 5) and intra-day (n = 5) assessments stand at 1.5 % and 1.4 %, respectively. Our proposed approach can effectively enrich an ovalbumin (OVA) solution with concentrations as low as 1.0 × 10−11 mol/L, resulting in enrichment rates of 107 to 108 times. The interference deviations of five substances relative to OVA lie within the range of − 2.0 % to + 2.0 %. The methodology successfully enriches glycoproteins from egg white samples diluted by a factor of 1 × 106, demonstrating that the proposed method is remarkably suitable for enriching glycoproteins from authentic samples. [ABSTRACT FROM AUTHOR]

Pinacolato boronates (Bpin) with an empty p‐orbital on boron stabilize an adjacent carbon radical, in contrast to diethanolamino boronates [B(DEA)] where the boron is sp3‐hybridized. By alternately placing a pinacol or diethanolamine moiety on the boron atom, thus stabilizing or not stabilizing the corresponding adjacent radical, it is possible to control the behavior of α‐boronyl xanthates and construct a large variety of terminal or internal boronates in a modular fashion. The remarkable tolerance of polar groups and the ability to introduce quaternary centers are particularly noteworthy features of this process. [ABSTRACT FROM AUTHOR]

A combination of copper iodide and phenanthroline as the ligand is an efficient catalyst for Suzuki‐Miyaura cross‐coupling of highly fluorinated boronate esters (aryl−Bpin) with aryl iodides and bromides to generate fluorinated biaryls in good to excellent yields. This method represents a nice alternative to traditional cross‐coupling methods which require palladium catalysts and stoichiometric amounts of silver oxide. We note that π⋅⋅⋅π stacking interactions dominate the molecular packing in the partly fluorinated biaryl crystals investigated herein. They are present either between the arene and perfluoroarene, or solely between arenes or perfluoroarenes, respectively. [ABSTRACT FROM AUTHOR]

• An on-line enrichment method of glycoproteins using capillary electrophoresis was developed. • The capillary coated with PGMA@APBA microparticles was prepared automatically using the CE instrument. • The on-line enrichment of glycoproteins can be accomplished within 2 min. • The RSD of peak area of run-to-run and batch-to-batch is below 1.5%. The column can be consecutively used for about 60 runs. The method was applied to enrich glycoproteins from 1 × 1012-fold diluted real egg white sample. A facial and rapid method for glycoproteins enrichment by capillary electrophoresis was developed. The 3-aminophenylboronic acid-functionalized poly(glycidyl methacrylate) microparticles (PGMA@APBA) were attached to the capillary inlet (length of ∼1.5 cm) by electrostatic self-assemble action to prepare a partially coated capillary column. The process is simple and reversible, allowing for easy renewal of the PGMA@APBA coating when its enrichment efficiency decreases. By utilizing the coated column, glycoproteins can be enriched within 2 min. The column exhibits a specific enrichment for glycoproteins and can be consecutively used for approximately 60 runs. The relative standard deviations (RSDs) of peak area of run-to-run (n = 5) and batch-to-batch (n = 3) were 1.5 % and 1.0%, respectively. The method was successfully applied to enrich glycoproteins from 1 × 1012-fold diluted real egg white sample, indicating its practical applicability. [ABSTRACT FROM AUTHOR]

[Display omitted] Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and conditions, such as cancer, infections, inflammatory and neurological disorders. Notably, boron has proven to also be a valuable element for the development of inhibitors of the metalloenzymes carbonic anhydrases (CAs), a class of drug targets with significant potential in medicinal chemistry. Incorporating boron into carbonic anhydrase inhibitors (CAIs) can modulate the ligand ability to recognize the target and/or influence selectivity towards different CA isoforms, using the tail approach and boron-based tails. The electron-deficient nature of boron and its associated properties have also led to the discovery of novel zinc-binding CAIs, such as boronic acids and the benzoxaboroles, capable of inhibiting the CAs upon a Lewis acid-base mechanism of action. The present manuscript reviews the state-of-the-art of boron-based CAIs. As research in the applications of boron compounds in medicinal chemistry continues, it is anticipated that new boron-based CAIs will soon expand the current array of such compounds. However, further research is imperative to fully unlock the potential of boron-based CAIs and to advance them towards clinical applications. [ABSTRACT FROM AUTHOR]

Thiol peroxidases (TP) are ubiquitous and abundant antioxidant proteins of the peroxiredoxin and glutathione peroxidase families that can catalytically and rapidly reduce biologically relevant peroxides, such as hydrogen peroxide and peroxynitrite. However, the TP catalytic cycle is complex, depending on multiple redox reactions and partners, and is subjected to branching and competition points that may limit their peroxide reductase activity in vivo. The goals of the present study were to demonstrate peroxynitrite reductase activity of TP members in live cells in real time and to evaluate its catalytic characteristics. To these ends, we developed a simple fluorescence assay using coumarin boronic acid (CBA), exploiting that fact that TP and CBA compete for peroxynitrite, with the expectation that higher TP peroxynitrite reductase activity will lower the CBA oxidation. TP peroxynitrite reductase activity was evaluated by comparing CBA oxidation in live wild type and genetically modified Δ8 (TP-deficient strain) and Δ8+TSA1 (Δ8 strain that expresses only one TP member, the TSA1 gene) Saccharomyces cerevisiae strains. The results showed that CBA oxidation decreased with cell density and increased with increasing peroxynitrite availability. Additionally, the rate of CBA oxidation decreased in the order Δ8 > Δ8+TSA1 > WT strains both in control and glycerol-adapted (expressing higher TP levels) cells, showing that the CBA competition assay could reliably detect peroxynitrite in real time in live cells, comparing CBA oxidation in strains with reduced and increased TP expression. Finally, there were no signs of compromised TP peroxynitrite reductase activity during experimental runs, even at the highest peroxynitrite levels tested. Altogether, the results show that TP is a major component in the defense of yeast against peroxynitrite insults under basal and increasing stressful conditions.

Abstract: Hydrogels with tunable viscoelasticity hold promise as materials that can recapitulate many dynamic mechanical properties found in native tissues. Here, covalent adaptable boronate bonds are exploited to prepare hydrogels that exhibit fast relaxation, with relaxation time constants on the order of seconds or less, but are stable for long‐term cell culture and are cytocompatible for 3D cell encapsulation. Using human mesenchymal stem cells (hMSC) as a model, the fast relaxation matrix mechanics are found to promote cell–matrix interactions, leading to spreading and an increase in nuclear volume, and induce yes‐associated protein/PDZ binding domain nuclear localization at longer times. All of these effects are exclusively based on the hMSCs' ability to physically remodel their surrounding microenvironment. Given the increasingly recognized importance of viscoelasticity in controlling cell function and fate, it is expected that the synthetic strategies and material platform presented should provide a useful system to study mechanotransduction on and within viscoelastic environments and explore many questions related to matrix biology. [ABSTRACT FROM AUTHOR]

[Display omitted] • Surface of TiO 2 functionalized with amino and boronic acid moieties. • Amino stabilized boronate allows to selectively bind 1,2 diols under neutral pH. • Protection and recovery of 1,2 diols and simultaneous degradation of other pollutants. TiO 2 has been functionalized by using 3-aminopropyltrimethoxy silane (APTMS) and 4-carboxyphenylboronic acid (CPBA). Solid state NMR indicated that ca. 50% of the amino groups did not react with CPBA, and stabilized vicinal boronate groups even at circumneutral pH, i.e. outside the stability range of isolated boronate ions (pH > 8.8). The as demonstrated existence of stabilized boronate groups at circumneutral pH has been used to carry out the proof of concept for selective photocatalytic degradations. In particular, irradiating bare TiO 2 induced the expected oxidation of two model pollutants (alizarin red, AR and methylene blue, MB) dissolved in the reacting medium. Instead, the presence of boronate groups at the surface of TiO 2 prevented the photocatalytic degradation of adsorbed AR, while simultaneously allowing oxidation of MB. Results are of environmental interest, and pave the way to processes enabling recovery of valuable compounds and simultaneous photocatalytic degradation of other noxious and/or useless species present in the same stream. [ABSTRACT FROM AUTHOR]

A concise synthesis of helicascolides A, B and C was achieved in three to five steps from commercially available materials. The key transformations of the synthesis include an Evans-Metternich anti -aldol reaction of the known β-keto imide 10 and strategic base-mediated one-pot cyclization/alkylation. Based on the new chemical evidence of ring-opening reaction of β-keto ester under biocompatible basic conditions, Krohn’s proposal for the biosynthetic relationship between helicascolide A ( 1 ) and a naturally co-existing acyclic dienone 4 was suggested in a reverse manner. [ABSTRACT FROM AUTHOR]

Tri(2-furyl)phosphine is a superior ligand to triphenylphosphine in the rhodium-catalysed hydroboration of alkynes with pinacolborane to yield alkenylboronates. In general the reactions are faster and the products are cleaner. [ABSTRACT FROM AUTHOR]

A series of MIDA ( N-methylimino diacetic acid) boronates carrying 4-alkoxy, 3,4-bisalkoxy, or 3,4,5-trisalkoxyphenyl substituents were synthesized and their mesomorphic properties characterized by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X-ray diffraction (XRD) techniques such as small- and wide-angle X-ray scattering (SAXS and WAXS, respectively). Most derivatives were liquid crystalline. In the case of mono- and bisalkoxy-substituted derivatives, C6 chains already induced smectic A (SmA) mesophases despite the bulky MIDA head group. With increasing chain length, columnar hexagonal (Colh) phases replaced SmA phases in the disubstituted series. Quantum chemical calculations on a series of MIDA boronates show that the B−N bond is a dative bond with a positive charge on the boron atom and negative charges on the nitrogen and oxygen atoms. In addition, no π-interaction between the aryl moiety and B−N bond was found, thus the mesogenic unit is electronically decoupled from the MIDA head group. These theoretical findings were supported by IR and Raman spectra as well as by asingle crystal structure analysis of 4-ethoxyphenyl MIDA boronate. Calculations of the electrostatic potential of the MIDA boronate reveal a special polarity pattern that can support the formation of a two-dimensional network and is likely to explain the liquid crystalline self-assembly. The absence of any electronic cross-talk between the MIDA head group and B-aryl or B-alkyl substituents allows the efficient tailoring of the mesophase type through variation of the substituents. [ABSTRACT FROM AUTHOR]

Herein, we report the evaluation and synthesis of a reaction based fluorescent probe DCM‐Bpin for the detection of peroxynitrite (ONOO−). DCM‐Bpin exhibits selective fluorescence off‐on response for ONOO− over other reactive oxygen species, including H2O2. Moreover, DCM‐Bpin is biocompatible and has been used to visualize exogenous ONOO− in HeLa cells. [ABSTRACT FROM AUTHOR]

Chiral biphenols catalyze the asymmetric Petasis borono-Mannich allylation of aldehydes and amines through the use of a bench-stable allyldioxaborolane. The reaction proceeds via a two-step, one-pot process and requires 2-8 mole % of 3,3′-Ph2-BINOL as the optimal catalyst. Under microwave heating the reaction affords chiral homoallylic amines in excellent yields (up to 99 %) and high enantioselectivies (er up to 99:1). The catalytic reaction is a true multicomponent condensation reaction whereas both the aldehyde and the amine can possess a wide range of structural and electronic properties. Use of crotyldioxaborolane in the reaction results in stereodivergent products with anti- and syn-diastereomers both in good diastereoselectivities and enantioselectivities from the corresponding E- and Z-borolane stereoisomers. [ABSTRACT FROM AUTHOR]

The boron (Z = 5) element is unique. Boron-based (nano-)materials are equally unique. Accordingly, the present special issue is dedicated to crystalline boron-based (nano-)materials and gathers a series of nine review and research articles dealing with different boron-based compounds. Boranes, borohydrides, polyhedral boranes and carboranes, boronate anions/ligands, boron nitride (hexagonal structure), and elemental boron are considered. Importantly, large sections are dedicated to fundamentals, with a special focus on crystal structures. The application potentials are widely discussed on the basis of the materials' physical and chemical properties. It stands out that crystalline boron-based (nano-)materials have many technological opportunities in fields such as energy storage, gas sorption (depollution), medicine, and optical and electronic devices. The present special issue is further evidence of the wealth of boron science, especially in terms of crystalline (nano-)materials. [ABSTRACT FROM AUTHOR]

A demethylative direct borylation is reported, which was applied to the synthesis of benzo[ fg]tetracenes containing boronate ester, amide, and thioester substructures. Depending on the heteroatom adjacent to boron, the molecules showed characteristic photophysical properties, molecular arrangements, and chemical stabilities. The key to the successful synthesis is the appropriate choice of the boron source and Brønsted base. The versatility of the direct borylation was demonstrated by the synthesis of a boronate-based benzo[ hi]hexacene. [ABSTRACT FROM AUTHOR]

A new boron-dipyrromethene (BODIPY) derivative bearing a boronate group ( 1 ) had been designed and synthesized as a colorimetric and fluorescent chemosensor for F − and CN − with no interference from each other. The addition of F − and CN − to 1 in THF solution induced a rapid color change from rose pink to indigo and faint pink, respectively. At the same time, the emission color of the 1 changed from red to indigo and green in presence of F − and CN − , respectively. 19 F and 1 H NMR spectra indicated that the preferential binding of cyanide occurred at the boron center of BODIPY core. On the other hand, fluoride binding occurred at the boron center of BODIPY core and boronate moiety. [ABSTRACT FROM AUTHOR]

Despite the extensive range of investigations on boronic acids (R-B(OH)2), some aspects of their reactivity still need to be explored. This is the case for the coordination chemistry of boronate anions (R-B(OH)3-), which has only recently been started to be studied. The purpose of this review is to summarize some of the key features of boronate ligands (and of their cyclic derivatives, benzoxaborolates) in materials: (i) coordination properties; (ii) spectroscopic signatures; and (iii) emerging applications. [ABSTRACT FROM AUTHOR]

A new click bioorthogonal reaction system was devised to enable the fast ligation ( kON≈340 m−1 s−1) of conjugatable derivatives of a rigid cyclic diol (nopoldiol) and a carefully optimized boronic acid partner, 2-methyl-5-carboxymethylphenylboronic acid. Using NMR and fluorescence spectroscopy studies, the corresponding boronates were found to form reversibly within minutes at low micromolar concentration in water, providing submicromolar equilibrium constant ( Keq≈105-106 m−1). Efficient protein conjugation under physiological conditions was demonstrated with model proteins thioredoxin and albumin, and characterized by mass spectrometry and gel electrophoresis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Variation of Iminodiacetic acid (IDA) boronates and core structures to investigate the influence on molecular self-assembly. • Synthesis of four novel families of IDA boronates. • Structural modification of aryl or heteroaryl units and N -substituents of IDA boronates. • Characterization of liquid crystalline properties by POM, DSC and X-ray diffraction (SAXS & WAXS). • Broad mesophases of smectic and columnar geometries. The highly polar N -methyl iminodiacetic acid (MIDA) unit induces liquid crystalline self-assembly when the MIDA boronate is attached to conventional mono-, bis- or trisalkoxyphenyl mesogens. In order to understand the influence of the rigid mesogenic unit and the N -substituent on the mesomorphic properties six series of IDA boronates carrying N -ethyl in combination with classic mesogenic aryl units (Ph(n) k EIDA , n = 10 – 16, k = 1 – 3), or N -methyl in combination with bend meta -alkoxyphenyl (Ph(n) meta MIDA), linear alkoxy-pyridyl (Pyr(n) 1 MIDA) and -pyrimidinyl (Pym(n) 1 MIDA) respectively, were prepared. Analysis by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (WAXS, SAXS) revealed that N -ethyl and bend-shaped aryl units mostly lowered the clearing transition temperatures, decreasing the tendency for thermal decomposition and affected the preference of SmA phases, while heterocyclic units were beneficial for stable SmA phases. [ABSTRACT FROM AUTHOR]

Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both in vitro and in vivo . Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications.

A novel complex of 4-picoline (4-Pic) with 4-trifluoromethylphenyl catechol boronate (TFCB) has been prepared and characterized by H NMR, C NMR, and X-ray diffraction analysis. When crystallized by evaporation from toluene a remarkable co-crystal was formed: 5(4-Pic·TFCB)·4-Pic (monoclinic P2, a = 13.4536(2) Å, b = 24.4320(3) Å, c = 14.0960(2) Å, β = 96.4340(10)°, vol. = 4604.15(11) Å, Z = 2). The likely cause of the co-crystallization is π-stacking between complexed and free 4-Pic. Graphical Abstract: A novel picoline-boronate complex has been prepared and characterized by H NMR, C NMR, and X-ray diffraction analysis. The solid-state structure of this simple complex reveals a remarkable co-crystal of 5(4-Pic·TFCB)·4-Pic. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

An on-line high-performance liquid chromatography (HPLC) method for the rapid and selective detection of boronic acids in complex mixtures was developed. After optimization experiments at an HPLC flow rate of 0.40 mL/min, the HPLC-separated analytes were mixed post-column with a solution of 75 μM alizarin and 0.1% triethylamine in acetonitrile, which was delivered at a flow rate of 0.60 mL/min. The reaction between alizarin and boronic acids occurred in a reaction coil of dimensions of 3.5 m × 0.25 mm at a temperature of 50 °C, resulting in fluorescent complexes that were detected as positive peaks by a fluorescence detector ( λ exc 469 nm and λ em 610 nm). The method enabled the selective detection of various boronic acids and derivatives, with a limit of detection of phenylboronic acid of 1.2 ng or 1 μM. It could successfully monitor the progress of two organic reactions involving boronic acid-containing compounds, and provided useful insights into the course of the reactions. [ABSTRACT FROM AUTHOR]

Macrophage-derived nitric oxide ( • NO) participates in cytotoxic mechanisms against diverse microorganisms and tumor cells. These effects can be mediated by • NO itself or • NO-derived species such as peroxynitrite formed by its diffusion-controlled reaction with NADPH oxidase-derived superoxide radical anion (O 2 • − ). In vivo , the facile extracellular diffusion of • NO as well as different competing consumption routes limit its bioavailability for the reaction with O 2 • − and, hence, peroxynitrite formation. In this work, we evaluated the extent by which • NO diffusion to red blood cells (RBC) can compete with activated macrophages-derived O 2 • − and affect peroxynitrite formation yields. Macrophage-dependent peroxynitrite production was determined by boron-based probes that react directly with peroxynitrite, namely, coumarin-7-boronic acid (CBA) and fluorescein-boronate (Fl-B). The influence of • NO diffusion to RBC on peroxynitrite formation was experimentally analyzed in co-incubations of • NO and O 2 • − -forming macrophages with erythrocytes. Additionally, we evaluated the permeation of • NO to RBC by measuring the intracellular oxidation of oxyhemoglobin to methemoglobin. Our results indicate that diluted RBC suspensions dose-dependently inhibit peroxynitrite formation, outcompeting the O 2 • − reaction. Computer-assisted kinetic studies evaluating peroxynitrite formation by its precursor radicals in the presence of RBC are in accordance with experimental results. Moreover, the presence of erythrocytes in the proximity of • NO and O 2 • - -forming macrophages prevented intracellular Fl-B oxidation pre-loaded in L1210 cells co-cultured with activated macrophages. On the other hand, Fl-B-coated latex beads incorporated in the macrophage phagocytic vacuole indicated that intraphagosomal probe oxidation by peroxynitrite was not affected by nearby RBC. Our data support that in the proximity of a blood vessel, • NO consumption by RBC will limit the extracellular formation (and subsequent cytotoxic effects) of peroxynitrite by activated macrophages, while the intraphagosomal yield of peroxynitrite will remain unaffected. [ABSTRACT FROM AUTHOR]

It is generally accepted that the structural characteristics of a molecule determine its physical and electrochemical properties. In this study, the conformations and some electrochemical properties of various boronates were investigated through computational study using density functional theory (DFT) with the Becke's three-parameter hybrid method utilizing the Lee-Young-Parr correlation functional (B3LYP). After initial energy optimization using Møller-Plesset perturbation theory (MP2), the conformational preferences and energetics were investigated using DFT calculations and the 6-31G(d,p) basis set in vacuo. The calculations and first results show that the ethyleneoxyboronates can be expected to perform well as redox shuttles, and boron-based redox shuttles can contribute to overcharge protection and safer batteries. HOMO-LUMO energy differences also indicate higher reactivities of the boronates, contributing to better solid electrolyte interphase formation. [ABSTRACT FROM AUTHOR]

Automation steht wieder auf der Tagesordnung! Der erste automatisierte, iterative C ‐ C ‐ Kupplungsprozess nutzt die beiden Gesichter von MIDA ‐ Boronaten. Es werden die Möglichkeiten und Herausforderungen offenbart, wie iterative Synthesen mit komplexen, bifunktionalisierten Bausteinen unter Nutzung von „Liquid ‐ Handling”︁ ‐ Systemen sogar Naturstoffsynhesen möglich machen. [ABSTRACT FROM AUTHOR]

New tetrasubstituted pentiptycenequinone derivatives 1 and 2 having two sets of diol moieties in a syn orientation were synthesized from the corresponding 2,3-disubstituted anthracene derivatives. The semicircular scaffold of these molecules is expected to be useful to create a belt-like structure having an aromatic π-wall. Indeed, the reaction of 1 with 1,4-phenylenediboronic acid or 4,4′-biphenyldiboronic acid quantitatively gave a 2:2 macrocyclic product via boronate ester formation. The efficient formation of these cyclic structures can be explained by favorable intramolecular cyclization at the final step. [ABSTRACT FROM AUTHOR]

A two-step synthesis of structurally diverse pyrrole-containing bicyclic systems is reported. ortho-Nitro-haloarenes coupled with vinylic N-methyliminodiacetic acid (MIDA) boronates generate ortho-vinyl-nitroarenes, which undergo a 'metal-free' nitrene insertion, resulting in a new pyrrole ring. This novel synthetic approach has a wide substrate tolerance and it is applicable in the preparation of more complex 'drug-like' molecules. Interestingly, an ortho-nitro-allylarene derivative furnished a cyclic β-aminophosphonate motif. [ABSTRACT FROM AUTHOR]

Boronate-based fluorescent probes are widely used for the imaging of hydrogen peroxide (H 2 O 2). However, their selectivity might be subjected to the interference of other reactive oxygen species, especially peroxynitrite (ONOO-), due to the reaction of boronates with ONOO- being several orders of magnitude faster than with H 2 O 2. This work highlights a doubly activated electrophilicity-increasing strategy to develop a boronate-based fluorescent probe THMP for selective imaging of H 2 O 2 over ONOO-, where a boronate-modified pyridiniumylacrylonitrile is grafted on the 2-(2′-hydroxy-3′-methoxyphenyl) benzothiazole scaffold. Specifically, the boronate oxidation of THMP by H 2 O 2 leads to the release of the free fluorophore THMP-N, triggering a ratiometric fluorescence response from red to green. The presence of a doubly activated electrophilic site on the carbon-carbon double bond of THMP, by both the strong electron-withdrawing cyano group and the pyridinium moiety, allows selective oxidative cleavage of the double bond by ONOO- to an aldehyde HMBT-CHO, thereby excluding the interference of ONOO- in monitoring H 2 O 2. With the aid of the probe, we successfully visualized increased levels of H 2 O 2 during ferroptosis of HepG2 cells, and burst of H 2 O 2 in brains of live mice during cerebral ischemia reperfusion injury. [Display omitted] • Highlighting a doubly activated electrophilicity-increasing strategy. • Developing a boronate-based fluorescent probe THMP based on the strategy. • Selective imaging of H 2 O 2 over ONOO- by THMP. • Detailed mechanistic investigation. • Visualizing H 2 O 2 in brains of live mice during cerebral ischemia reperfusion. [ABSTRACT FROM AUTHOR]

Boronate, boronic acid, cycloadditions, C-C coupling, pyrrolidine Keywords: boronate; boronic acid; cycloadditions; C-C coupling; pyrrolidine EN boronate boronic acid cycloadditions C-C coupling pyrrolidine 1 1 1 09/30/22 20220927 NES 220927 B 1,3-Dipolar cycloadditions b of azomethine ylide (three atoms highlighted in yellow) and a broad scope of alkenyl boronates (the former C=C bond is highlighted in green) provide bi- and trifunctional 3-borylated pyrrolidines with diverse substitution patterns (including fused and spirocyclic ones) valuable for synthetic and medicinal chemistry. Cover Feature: Synthesis of 3-Borylated Pyrrolidines by 1,3-Dipolar Cycloaddition of Alkenyl Boronates and Azomethine Ylide (Chem. Eur. J. 54/2022). [Extracted from the article]

The boron (Z = 5) element is unique. Boron-based (nano-)materials are equally unique. Accordingly, the present special issue is dedicated to crystalline boron-based (nano-)materials and gathers a series of nine review and research articles dealing with different boron-based compounds. Boranes, borohydrides, polyhedral boranes and carboranes, boronate anions/ligands, boron nitride (hexagonal structure), and elemental boron are considered. Importantly, large sections are dedicated to fundamentals, with a special focus on crystal structures. The application potentials are widely discussed on the basis of the materials’ physical and chemical properties. It stands out that crystalline boron-based (nano-)materials have many technological opportunities in fields such as energy storage, gas sorption (depollution), medicine, and optical and electronic devices. The present special issue is further evidence of the wealth of boron science, especially in terms of crystalline (nano-)materials.

Despite the extensive range of investigations on boronic acids (R-B(OH)2), some aspects of their reactivity still need to be explored. This is the case for the coordination chemistry of boronate anions (R-B(OH)3−), which has only recently been started to be studied. The purpose of this review is to summarize some of the key features of boronate ligands (and of their cyclic derivatives, benzoxaborolates) in materials: (i) coordination properties; (ii) spectroscopic signatures; and (iii) emerging applications.