Inhibitors of monoamine oxidases (MAOs) are of interest for the treatment of neurodegenerative disorders and other human pathologies. In this frame, the present work describes different synthetic strategies to obtain MAO inhibitors via the coupling of the aminocoumarin core with arylsulfonyl chlorides followed by copper azide-alkyne cycloaddition, leading to coumarin-sulfonamide-nitroindazolyl-triazole hybrids. The nitration position on the coumarin moiety was confirmed through nuclear magnetic resonance spectroscopy and molecular electron density theory in order to elucidate the molecular mechanism and selectivity of the electrophilic aromatic substitution reaction. The coumarin derivatives were evaluated for their inhibitory potency against monoamine oxidases and cholinesterases. Molecular docking calculations provided a rational binding mode of the best compounds in the series with MAO A and B. The work identified hybrids 14a-c as novel MAO inhibitors, with a selective action against isoform B, of potential interest to combat neurological diseases.

The Maillard reaction is a vital part of food processing, involving a vast number of complex reaction pathways, resulting in high-molecular-weight colorants. So far, studies have been focused on the conversion of carbohydrates and amino compounds, but the literature elaborating the contribution of phenolic compounds to the formation of the colored end-products is still rare. The aim of this study was to characterize early reactions, underlying the formation of phenol-containing melanoidins. For this purpose, binary model systems of the prominent phenolic compounds caffeic acid and ferulic acid combined with α-dicarbonyl compounds typically formed in the Maillard reaction such as glyoxal, methylglyoxal, and diacetyl were analyzed after heat treatment. High-resolution mass spectrometry revealed that decarboxylation, aromatic electrophilic substitution, and nucleophilic addition are important reaction steps that lead to colored heterogeneous oligomers. Polymerization was favored for phenolic compounds with a high electron density in the aromatic system and for α-dicarbonyl compounds carrying aldehyde functions.

A straightforward approach is employed to synthesize methylene-bridged poly(hetero aromatic)s based on furan, pyrrole, thiophene, and thiophene derivatives. The process involves an electrophilic aromatic substitution reaction facilitated by a visible light-initiated system consisting of manganese decacarbonyl and an iodonium salt. The approach mainly relies on the formation of halomethylium cation, the attack of this cation to heteroaromatic, regeneration of methylium cation on the heteroaromatic, and reactivity differences between halomethylium and heteroaromatic methylium cations for successful polymerizations. This innovative synthetic strategy lead to the formation of polymers with relatively high molecular weights as the stoichiometric imbalance between the comonomers increased. Accordingly, these newly obtained polymers exhibit remarkable fluorescence properties, even at excitation wavelengths as low as 330 nm. Moreover, by harnessing the halogens at chain ends of homopolymers, block copolymers are successfully synthesized, offering opportunities for tailored applications in diverse fields.

Agelastatin A is a marine alkaloid with potent biological activity. To date, at least 17 different strategies have achieved its total synthesis, along with many analogues. The present study focuses on the acidity stability of some N-methyl derivatives of agelastatin A. The study made use of chemical reactions and spectroscopic acquisitions. The chemical structure of some derivatives can undergo a profound rearrangement. The results could shed light on the mechanism of action of agelastatin A and suggest the preparation of analogues with improved pharmacological efficacy.

The reaction of N-phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound. The two last steps correspond to a Friedel-Crafts acylation reaction, the product of the second reaction being the tetrahedral intermediate of an electrophilic aromatic substitution reaction. However, the presence of the imino group adjacent to the aromatic ring strongly stabilizes the corresponding intermediate, being the reaction product when the ortho positions are occupied by t-butyl substituents. This domino reaction shows a great similitude with the Brønsted acid catalyzed Povarov reaction. Although N-phenyl iminoborane can experience a formal [2+2] cycloaddition reaction with benzaldehyde, its higher activation Gibbs free energy compared to the intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent, 6.6 kcal·mol-1, prevents the formation of the formal [2+2] cycloadduct. The present MEDT study provides a different vision of the molecular mechanism of these reactions based on the electron density.

Sulfonated-polychlorinated biphenyls (sulfonated-PCBs) are a newly discovered class of PCB metabolites. They were observed for the first time in polar bear serum and lately, in soil, together with hydroxy-sulfonated-PCBs. Their presence is ubiquitous in soils, and their estimated physical chemical properties show high mobility in water, compared to the parent compounds. However, no single pure standards exist so far and therefore their quantification in the environmental matrices is not accurate. Additionally, pure standards are needed to experimentally determine their physical chemical properties, as well as the ecotoxicological and toxicological characteristics. In the present work, the challenging goal of preparing a polychlorinated biphenyl monosulfonic acid was achieved exploring different synthetic approaches, along which the selection of the starting material resulted in a crucial point. Using PCB-153 (2,2\'-4,4\'-5,5\'-hexachloro-1,1\'-biphenyl) the synthesis afforded, as the major species, a side compound. On the contrary, the use of PCB-155 (2,2\'-4,4\'-6,6\'-hexachloro-1,1\'-biphenyl), a symmetric hexachlorobiphenyl derivative showing chlorine atoms at all the ortho positions, gave the target sulfonated-PCB compound. In this case, sulfonation was successfully carried out through a two-step procedure, involving chlorosulfonylation and the subsequent hydrolysis of the chlorosulfonyl intermediate.

This paper presents the use of O,S-acetals in a new modification of the oxo-Friedel-Crafts-Bradsher cyclization. In this reaction, under mild reaction conditions (25 °C), three- and four-ring fused RO-acenes (major) and/or HO(CH2)2S-acenes (minor) are formed, the latter products having never been observed before in this type of cyclization. In this way, two electronically different fluorophores could be obtained in a single cyclization reaction, one of them having strong electron donor properties (+M effect of alkoxy groups) and the other having donor-acceptor properties (+M and -I effects of the HO(CH2)2S-group, Hammett\'s constants). Further increasing the reaction temperature, HCl concentration or prolonging reaction time, surprisingly, yielded a 2:1 mixture of cis and trans dimeric isomers, as the only products of this cyclization. The DFT calculations confirmed a greater stability of the cis isomer compared to the trans isomer. The formation of unexpected dimeric products and HO(CH2)2S-acenes sheds light on the mechanism of oxo-Friedel-Crafts-Bradsher cyclization, involving competitive O/S atom protonation in strained O,S-acetals and in strain-free side groups of intermediate species.

The browning of plant-based food is commonly understood to result from the enzymatic polymerization of phenolic compounds to pigments, called melanin. However, during the thermal treatment of food, enzymes are deactivated, and non-enzymatic reactions predominate. The extent of the contribution of phenolic compounds to these non-enzymatic reactions has been speculated (\"melanin-like vs. melanoidin-like\"), but the literature is limited. Therefore, the aim of the present study was to investigate the heat-induced reactions of caffeic acid (CA), para-coumaric acid (CS), ferulic acid (FA), hydrocaffeic acid (HC), and 5-O-caffeoylquinic acid (CGA) under dry conditions. The model systems were characterized by color formation, reactant conversion, and antioxidant properties. Reaction products were analyzed by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Decarboxylation could be classified as the driving force for the observed color formation and was significantly impacted by the substitution of the aromatic system. Reaction products were found to contribute to an increase in the antioxidant properties of the model systems. The oligomers described in this study could be incorporated into food melanoidins, contributing to the color and antioxidant properties observed in roasted food rich in phenolic compounds, such as coffee or cocoa.

Herein, a straightforward synthesis method for highly mesoporous molybdenum oxide has been demonstrated via use of inverse micelles and molybdenum-oxo cluster formation. The synthesized catalyst is stable, crystalline, and MoO3 phase pure, as confirmed through thermogravimetric analysis, X-ray diffraction, and X-ray photoelectron spectroscopy. Further results from electron paramagnetic resonance, Raman spectroscopy, and UV-vis spectroscopy confirm the MoO3 phase purity. Chemisorption studies reveal that the synthesized material is 65 times more active than its commercial parts. The quantitative value of ammonia chemisorption for the synthesized catalyst is 1270 μmol/g, whereas the commercial catalyst only gives 22 μmol/g. These materials were tested for electrophilic substitution reactions since they are excellent solid acid. Electrophilic substitution of benzyl alcohol with toluene gives a >99% conversion with ∼80% of selectivity toward the methyl diphenylmethane product. The turnover number and turnover frequency values were calculated to be as high as 115 and 38, respectively. A substrate scope study shows that the reaction has preference toward electron-donating groups, whereas electron-withdrawing groups block the reaction. Based on the obtained results, a mechanism has been proposed.

The generation of ε-carbonyl cations and their reactions with nucleophiles is accomplished readily without transition metal cation stabilization, using the ε-bromide dienoate or dienone starting materials and GaCl3 or InCl3 catalysis. Arene nucleophiles are somewhat more straightforward than allyltrimethylsilane, but allyltrimethylsilane and propiophenone trimethysilyl enol ether each react successfully with InCl3 catalysis. The viability of these cations is supported by DFT calculations.