Synthesis, biological evaluation (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic) and molecular docking study of hydroxy methoxy benzoin/benzil analogous.

In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.

Microbial Synthesis of (S)- and (R)-Benzoin in Enantioselective Desymmetrization and Deracemization Catalyzed by Aureobasidium pullulans Included in the Blossom Protect™ Agent.

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.

Reactivity-Based Screening for Citrulline-Containing Natural Products Reveals a Family of Bacterial Peptidyl Arginine Deiminases.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a family of natural products defined by a genetically encoded precursor peptide that is processed by associated biosynthetic enzymes to form the mature product. Lasso peptides are a class of RiPP defined by an isopeptide linkage between the N-terminal amine and an internal Asp/Glu residue with the C-terminal sequence threaded through the macrocycle. This unique lariat topology, which typically provides considerable stability toward heat and proteases, has stimulated interest in lasso peptides as potential therapeutics. Post-translational modifications beyond the class-defining, threaded macrolactam have been reported, including one example of Arg deimination to yield citrulline (Cit). Although a Cit-containing lasso peptide (i.e., citrulassin) was serendipitously discovered during a genome-guided campaign, the gene(s) responsible for Arg deimination has remained unknown. Herein, we describe the use of reactivity-based screening to discriminate bacterial strains that produce Arg- versus Cit-bearing citrulassins, yielding 13 new lasso peptide variants. Partial phylogenetic profiling identified a distally encoded peptidyl arginine deiminase (PAD) gene ubiquitous to the Cit-containing variants. Absence of this gene correlated strongly with lasso peptide variants only containing Arg (i.e., des-citrulassin). Heterologous expression of the PAD gene in a des-citrulassin producer resulted in the production of the deiminated analog, confirming PAD involvement in Arg deimination. The PADs were then bioinformatically surveyed to provide a deeper understanding of their taxonomic distribution and genomic contexts and to facilitate future studies that will evaluate any additional biochemical roles for the superfamily.

Synthesis, crystal structures, antiproliferative activities and reverse docking studies of eight novel Schiff bases derived from benzil.

Eight novel Schiff bases derived from benzil dihydrazone (BDH) or benzil monohydrazone (BMH) and four fused-ring carbonyl compounds (3-formylindole, FI; 3-acetylindole, AI; 3-formyl-1-methylindole, MFI; 1-formylnaphthalene, FN) were synthesized and characterized by elemental analysis, ESI-QTOF-MS, 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. They are (1Z,2Z)-1,2-bis{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFI), C32H24N6, (1Z,2Z)-1,2-bis{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethane (BDHAI), C34H28N6, (1Z,2Z)-1,2-bis{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BMHMFI) acetonitrile hemisolvate, C34H28N6·0.5CH3CN, (1Z,2Z)-1,2-bis{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFN), C36H26N4, (Z)-2-{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFI), C23H17N3O, (Z)-2-{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethanone (BMHAI), C24H19N3O, (Z)-2-{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHMFI), C24H19N3O, and (Z)-2-{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFN) C25H18N2O. Moreover, the in vitro cytotoxicity of the eight title compounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four (BDHMFI, BDHFN, BMHMFI and BMHFN) are inactive and the other four (BDHFI, BDHAI, BMHFI and BMHAI) show severe toxicities against human A549 and mouse 4T1 cells, similar to the standard cisplatin. All the compounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex-dock function in SYBYL-X 2.0 software. Three target proteins, i.e. human ether-á-go-go-related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine-protein kinase PIM1, were chosen as the targets. Finally, the ligand-based structure-activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.

Structure reactivity relationship in the accelerated formation of 2,3-diarylquinoxalines in the microdroplets of a nebuliser.

Competition experiments in which 1,2-phenylenediamine, C6H4(NH2)2, condenses with equimolar quantities of benzil, (C6H5CO)2, and a 3,3'- or 4,4'-disubstituted benzil (XC6H4CO)2 (X = F, Cl, Br, CH3 or CH3O) to form a mixture of 2,3-diphenylquinoxaline and the corresponding 2,3-diarylquinoxaline (Ar = XC6H4) in the microdroplets produced in a nebuliser allow a Hammett relationship with a ρ value of 1.85 to be developed for this accelerated condensation in the nebuliser. This structure reactivity relationship reveals that an appreciable amount of negative charge builds up on the carbon of the carbonyl group of the benzil during the rate-limiting step of the reaction, thus confirming that this process involves nucleophilic addition of the 1,2-phenylenediamine to the benzil. In general, the presence of an electron donating substituent, particularly in the 4 and 4' positions, in the benzil retards the reaction, whereas an electron attracting substituent, especially in the 3 and 3' position, accelerates it.

Site-Selective Antibody Functionalization via Orthogonally Reactive Arginine and Lysine Residues.

Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine (Lys) residue embedded in a dual variable domain (DVD)-IgG1 format can be assembled with high precision and efficiency under mild conditions. Here we show that replacing the Lys with an arginine (Arg) residue affords an orthogonal ADC assembly that is site-selective and stable. X-ray crystallography confirmed the location of the reactive Arg residue at the bottom of a deep pocket. As the Lys-to-Arg mutation is confined to a single residue in the heavy chain of the DVD-IgG1, heterodimeric assemblies that combine a buried Lys in one arm, a buried Arg in the other arm, and identical light chains, are readily assembled. Furthermore, the orthogonal conjugation chemistry enables the loading of heterodimeric DVD-IgG1s with two different cargos in a one-pot reaction and thus affords a convenient platform for dual-warhead ADCs and other multifaceted antibody conjugates.

H2O2-responsive polymeric micelles with a benzil moiety for efficient DOX delivery and AIE imaging.

Nano drug delivery is a promising domain in biomedical theranostics and has aroused more and more attention in recent years. We report here an amphiphilic polymer TPG1, bearing a H2O2-sensitive benzil and an AIE fluorophore tetraphenylethene (TPE) unit, which is able to self-assemble into spherical nanosized micelles in aqueous solution. Doxorubicin (DOX) can be encapsulated into TPG1 micelles efficiently with the loading capability of up to 59% by weight. The benzil moiety could be cleaved via the Baeyer-Villiger type reaction in the presence of H2O2, leading to the decomposition of TPG1 micelles and release of DOX. In vitro studies indicated that DOX-loaded TPG1 micelles can be internalized by cancer cells, followed by unloading encapsulated DOX under the stimulation of H2O2. The drug release process can be monitored by the AIE fluorescence from the degradation products containing a TPE moiety. MTT assays against HeLa and HepG2 cancer cells demonstrated that DOX-loaded micelles showed good anticancer efficacy. The polymer TPG1 and the corresponding decomposed products showed great biocompatibility. Our data suggest that TPG1 has the potential to be employed for the controlled drug delivery system.

New mixed amino acids complexes of iron(III) and zinc(II) with isonitrosoacetophenone: Synthesis, spectral characterization, DFT study and anticancer activity.

New mixed Fe(III) and Zn(II) complexes with isonitrosoacetophenone (HINAP) and l-amino acids (such as l-histidine, l-phenylalanine and l-proline) have been synthesized and characterized by elemental analyses, UV-Vis, IR and ESR spectroscopy and thermal analyses. The values of molar conductance of the complexes in DMSO solution at 10-3 M concentration indicate their non-electrolyte nature. IR spectroscopy has revealed the coordination of deprotonated ligands to metal through nitrogen and oxygen atoms in an N2O2 arrangement. Density functional theory (DFT) calculations were performed using the hybrid functional of Truhlar and Zhao (M06) with basis set of double zeta quality LANL2DZ to evaluate the cis and trans coordination modes and to ascertain dipole moment, HOMO-LUMO energy gap, chemical hardness, softness and electrophilicity. The magnetic moments and ESR measurements suggest that there is an admixture of S = 5/2 and S = 1/2 spins in Fe(III) complexes. UV-Visible spectra indicate a distorted octahedral geometry around the metal ions. Thermal analyses show the presence of hydrated and coordinated water. The antimicrobial activity was investigated against (G+ and G-) bacteria (Staphylococcus aureus, bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa) and fungi (Candida albicans). The iron and zinc complexes were found to be more active against Gram-positive than Gram negative bacteria. They also show considerable growth inhibition against the fungi tested. In vitro antitumor activity assayed against cancer cell lines of the HEP2 type (cancer cells of the larynx) exhibited significant toxicity of the ligands and their mixed complexes.

Development of a fluorescent probe for detection of citrulline based on photo-induced electron transfer.

Peptidyl arginine deiminases (PADs) catalyze the post-translational deimination of peptidyl arginine residues to form citrulline residues. Aberrant citrullination of histones by one of the PAD isozymes, PAD4, is associated with various diseases, including rheumatoid arthritis, so high-throughput screening systems are needed to identify PAD4 inhibitors as chemical tools to investigate the role of PAD4, and as candidate therapeutic agents. Here, we utilized the addition-cyclization reaction between phenylglyoxal and citrulline under acidic conditions to design turn-on fluorescent probes for citrulline based on the donor-excited photoinduced electron transfer (d-PeT) mechanism. Among several derivatives of phenylglyoxal bearing a fluorescent moiety, we found that FGME enabled detection of citrulline without a neutralization process, and we used it to establish a simple methodology for turn-on fluorescence detection of citrulline.

Arginine-selective bioconjugation with 4-azidophenyl glyoxal: application to the single and dual functionalisation of native antibodies.

Here, we introduce 4-azidophenyl glyoxal (APG) as an efficient plug-and-play reagent for the selective functionalisation of arginine residues in native antibodies. The selective reaction between APG and arginines' guanidine groups allowed a facile introduction of azide groups on the monoclonal antibody trastuzumab (plug stage). These pre-functionalised antibody-azide conjugates were then derivatised during the "play stage" via a biorthogonal cycloaddition reaction with different strained alkynes. This afforded antibody-fluorophore and antibody-oligonucleotide conjugates, all showing preserved antigen selectivity and high stability in human plasma. Due to a lower content of arginines compared to lysines in native antibodies, this approach is thus attractive for the preparation of more homogeneous conjugates. This method proved to be orthogonal to classical lysine-based conjugation and allowed straightforward generation of dual-payload antibody.

Synthesis of benzil-o-carboxylate derivatives and isocoumarins through neighboring ester-participating bromocyclizations of o-alkynylbenzoates.

Bromide mediated neighboring ester-participating bromocyclizations of o-alkynylbenzoates are described here for the synthesis of benzil-o-carboxylates. 4-bromoisocoumarins are also synthesized when phenyl o-alkynylbenzoate is used as the substrate. Mechanistic studies suggest that the whole process is composed of an electrophilic bromocyclization and a dibromohydration-based ring-opening, and the neighboring ester group participates in the bromocyclization. Interestingly, the two oxygen atoms of the keto carbonyls in benzil-o-carboxylates are both derived from water. The electrophilic bromo source is in situ generated from the oxidation of bromide.

One-pot synthesis of a new 2-substituted 1,2,3-triazole 1-oxide derivative from dipyridyl ketone and isonitrosoacetophenone hydrazone: Nickel(II) complex, DNA binding and cleavage properties.

An efficient and simple one-pot synthesis of a new 1,2,3-triazole-1-oxide via reaction between isonitrosoacetophenone hydrazone and dipyridyl ketone in the EtOH/AcOH at room temperature has been developed smoothly in high yield. The reaction proceeds via metal salt free, in-situ formation of asymmetric azine followed by cyclization to provide 1,2,3-triazole 1-oxide compound. It has been structurally characterized. The 1:1 ratio reaction of the 1,2,3-triazole 1-oxide ligand with nickel(II) chloride gives the mononuclear complex [Ni(L)(DMF)Cl2], hexa-coordinated within an octahedral geometry. Characterization of the 1,2,3-triazole compound and its Ni(II) complex with FTIR, 1H and 13C NMR, UV-vis and elemental analysis also confirms the proposed structures of the compounds. The interactions of the compounds with Calf thymus DNA (CT-DNA) have been investigated by UV-visible spectra and viscosity measurements. The results suggested that both ligand and Ni(II) complex bind to DNA in electrostatic interaction and/or groove binding, also with a slight partial intercalation in the case of ligand. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H2O2). Both 1,2,3-triazole 1-oxide ligand and its nickel(II) complex show nuclease activity in the presence of hydrogen peroxide. DNA binding and cleavage affinities of the 1,2,3-triazole 1-oxide ligand is stronger than that of the Ni(II) complex.

Evaluation of chemical labeling methods for identifying functional arginine residues of proteins by mass spectrometry.

Arginine residues undergo several kinds of post-translational modifications (PTMs). These PTMs are associated with several inflammatory diseases, such as rheumatoid arthritis, atherosclerosis, and diabetes. Mass spectrometric studies of arginine modified proteins and peptides are very important, not only to identify the reactive arginine residues but also to understand the tandem mass spectrometry behavior of these peptides for assigning the sequences unambiguously. Herein, we utilize tandem mass spectrometry to report the performance of two widely used arginine labeling reagents, 1,2-cyclohexanedione (CHD) and phenylglyoxal (PG) with several arginine containing peptides and proteins. Time course labeling studies were performed to demonstrate the selectivity of the reagents in proteins or protein digests. Structural studies on the proteins were also explored to better understand the reaction sites and position of arginine residues. We found CHD showed better labeling efficiencies compared to phenylglyoxal. Reactive arginine profiling on a purified albumin protein clearly pointed out the cellular glycation modification site for this protein with high confidence. We believe these detailed mass-spectrometric studies will provide significant input to profile reactive arginine residues in large-scale studies; therefore, targeted proteomics can be performed to the short listed reactive sites for cellular arginine modifications.

Arginine selective reagents for ligation to peptides and proteins.

A new class of arginine-specific bioconjugation reagents for protein labeling has been developed. This method utilizes a triazolyl-phenylglyoxal group on the probe molecule that reacts selectively with the guandinyl group of Arg residues in a protein or peptide. The reaction proceeds in neutral to basic bicarbonate buffers and is selective for arginine residues in peptides and folded proteins. Importantly, the triazolyl-phenylglyoxal group can be introduced into complex molecules containing alkyne groups using CuAAC chemistry, providing a robust approach for the generation of phenylglyoxal reactive groups into molecules to be covalently attached onto the surface of proteins. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Chemiluminescent aptasensor capable of rapidly quantifying Escherichia Coli O157:H7.

Cost-effective and easy-to-use biosensor was developed for the rapid quantification and monitoring of Escherichia (E.) Coli O157:H7 in sample using E. Coli O157:H7 aptamer, graphene oxide (GO)/iron nanocomposites, and guanine chemiluminescence detection. E. Coli O157:H7 aptamer-conjugated 6-carboxyfluorescein (6-FAM) with excellent specificity captured E. Coli O157:H7 in a sample when the mixture was incubated for 1h at 37°C. Free E. Coli O157:H7 aptamers remaining in sample after the incubation were removed with GO/iron nanocomposites based on the principle of π-π stacking interaction between free aptamer and GO/iron nanocomposites. Then, E. Coli O157:H7 bound with aptamer-conjugated 6-FAM in sample emitted strong light when guanine chemiluminescent reagents (e.g., 3,4,5-trimethoxylphenylglyoxal hydrate, Tetra-n-propylammonium hydroxide) were added in the sample. The strength of light emitted in guanine chemiluminescence reaction was proportionally enhanced with the increase of E. Coli O157:H7 concentration. The limit of detection (LOD) of biosensor capable of quantifying E. Coli O157:H7 with good accuracy, precision, and reproducibility was as low as 4.5×10(3)cfu/ml. We expect that the rapid analytical system can be applied in the field of food safety as well as public health.

Self-assembly of Metallamacrocycles Employing a New Benzil-based Organometallic Bisplatinum(II) Acceptor.

A benzil-based semi-rigid dinuclear-organometallic acceptor 4,4'-bis[trans-Pt(PEt(3))(2)(NO(3))(ethynyl)]benzil (bisPt-NO(3)) containing a Pt-ethynyl functionality was synthesized in good yield and characterized by multinuclear NMR ((1)H, (31)P, and (13)C), electrospray ionization mass spectrometry (ESI-MS), and single-crystal X-ray diffraction analysis of the iodide analogue bisPt-I. The stoichiometric (1:1) combination of the acceptor bisPt-NO(3) separately with four different ditopic donors (L(1)-L(4); L(1) = 9-ethyl-3,6-di(1H-imidazol-1-yl)-9H-carbazole, L(2) = 1,4-bis((1H-imidazol-1-yl)methyl)benzene, L(3) = 1,3-bis((1H-imidazol-1-yl)methyl)benzene and L(4) = 9,10-bis((1H-imidazol-1-yl) methyl)anthracene) yielded four [2 + 2] self-assembled metallacycles M(1)-M(4) in quantitative yields, respectively. All these newly synthesized assemblies were characterized by various spectroscopic techniques (NMR, IR, ESI-MS) and their sizes/shapes were predicted through geometry optimization employing the PM6 semi-empirical method. The benzil moiety was introduced in the backbone of the acceptor bisPt-NO(3) due to the interesting structural feature of long carbonyl C-C bond (∼1.54 Å), which enabled us to probe the role of conformational flexibility on size and shapes of the resulting coordination ensembles.

Phenylglyoxal-based visualization of citrullinated proteins on Western blots.

Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline.

Synthesis, crystal structures and spectroscopic properties of triazine-based hydrazone derivatives; a comparative experimental-theoretical study.

We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (1H and 13C) spectroscopic techniques and finally confirmed unequivocally by single crystal X-ray diffraction analysis. Experimental geometric parameters and spectroscopic properties of the triazine based hydrazones are compared with those obtained from density functional theory (DFT) studies. The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric parameters of all four compounds showed excellent correlations with the results obtained from X-ray diffraction studies. The vibrational spectra show nice correlations with the experimental IR spectra. Moreover, the simulated absorption spectra also agree well with experimental results (within 10-20 nm). The molecular electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic properties) and first hyperpolarizability (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level of theory.

New duel fluorescent "on-off" and colorimetric sensor for Copper(II): Copper(II) binds through N coordination and pi cation interaction to sensor.

Schiff base derived from naphthylamine and benzil (L) binds to two Cu(2+) ions, one by coordination through N of the Schiff base and another by pi cation interaction through benzil rings. This bonding pattern determined by DFT calculation has been proved by matching electronic spectrum obtained from TDDFT calculation to the experimental one. L acts as "on-off" fluorescent and bare eye detectable colorimetric (purple color) sensor for Cu(2+) ion over the metal ions - Na(+), K(+), Ca(2+) Mn(2+), Co(2+) Ni(2+), Zn(2+), Pb(2+), Cd(2+), Hg(2+), Ag(+), Hg(2+) and Al(3+) in 1:1 v/v CH3CN:H2O. These metal ions do not interfere the fluorescent/colorimetric sensing. As fluorescent sensor the linear range of detection is 5×10(-5) to 3×10(-4)M and detection limit 10(-5)M.

Copper-catalyzed direct synthesis of diaryl 1,2-diketones from aryl iodides and propiolic acids.

Benzil derivatives such as diaryl 1,2-diketones are synthesized via the direct decarboxylative coupling reaction of aryl propiolic acids and their oxidation. The optimized conditions are that the reaction of aryl propiolic acids and aryl iodides is conducted at 140 °C for 6 h in the presence of 10 mol % CuI/Cu(OTf)2 and Cs2CO3, after which HI (aq) is added and further reacted. The method shows good functional group tolerance toward ester, aldehyde, cyano, and nitro groups. In addition, symmetrical diaryl 1,2-diketones are obtained from aryl iodides and propiolic acid in the presence of palladium and copper catalysts.