Heterocyclic Acids Research Articles

Desulfonation-associated direct amide bond formation between N-sulfonyl-1,2,3-triazoles with carboxylic acids

We have developed a highly N2-regioselective method for direct construction of amide bond from N-sulfonyl-1,2,3-triazoles and carboxylic acids in the presence of bases at 60 °C in air. The developed reaction provides the corresponding products with high yields (up to 90 %) and a broad substrate compatibility including aryl acids, heterocyclic acids, and alkyl acids. Mechanistic studies show that the reaction proceeds through a direct nucleophilic attack of N-sulfonyl-1,2,3-triazoles to carboxylate anions via a base- and water-involved synergistic desulfonation process. This work presents an unusual water-involved example for direct synthesis of amides utilizing readily available starting materials under mild conditions.

Enhancing bread anti-staling with glucose-derived Maillard reaction products: In-depth analysis of starches, gluten networks, and moisture status

In this study, six types of amino acids (Ala, Phe, Glu, Gly, Ser, and Lys) were combined with glucose to produce Maillard reaction products (MRPs) named G-Ala, G-Phe, G-Glu, G-Gly, G-Ser and G-Lys. The effect of MRPs on bread staling was evaluated through texture and sensory analyses during storage. Furthermore, the study comprehensively analyzed the anti-staling mechanisms of MRPs by examining moisture content, starches, and gluten network changes. The results indicated that G-Gly and G-Glu delayed bread staling, with G-Gly showing the most significant effect. Compared with control, the staling rate and starch crystallinity of G-Gly bread decreased by 24.07% and 7.70%, respectively. Moreover, G-Gly increased the moisture content (3.48%), weakly bound water mobility (0.77%), and α-helix content (1.00%) of bread. Component identification and partial least squares regression further confirmed the aldonic acid, heterocyclic acids and heterocyclic ketones in MRPs inhibit water evaporation, gluten network loosening, and starch degradation, thereby delaying bread staling.

Synthesis and anticonvulsive activity of new 1,3-diazaadamantane derivatives

The work is devoted to the synthesis and study of the neurotropic activity of some derivatives of 3,7-diazabicyclo/3.3.1/nonanes. For this, various 5,7-dialkyl, methylphenyl, diphenyl 1,3-diazaa-damantanes 1 were synthesized, which, upon interaction with acid chlorides of aliphatic, aromatic and heterocyclic acids, were converted into the corresponding 3,7-diazabicyclo/3.3.1/nonanes. The anticonvulsant activity of the synthesized compounds was studied. Among them, substances with pronounced anticorazole activity were identified.

Copper(II) and Zinc(II) Complexes with Heterocyclic Acid Anions and 3,5-Dimethylpyrazole: Synthesis, Structure, and Biological Properties

The reaction of copper(II) and zinc(II) acetates with 3-furancarboxylic (HFur) and 2-thiophenecarboxylic (HTph) acids with subsequent addition of 3,5-dimethylpyrazole (HDmpz) gave mononuclear complexes [M(L)2(HDmpz)2] (M = Cu(II), L = Fur– (I), Tph– (II); Zn(II), L = Fur– (III)). The structures of compounds I–III were determined by X-ray diffraction. According to X-ray diffraction data, I and II are isostructural: the central Cu(II) atom occurs in a square planar environment formed by two oxygen atoms of carboxylate anions and HDmpz nitrogen atoms; in III, the Zn atom is in the tetrahedral environment of two furoate anions and HDmpz molecules, thus forming the {MO2N2} groups. The complexes are additionally stabilized in the crystal by inter- (I and II) and intramolecular (III) hydrogen bonds. The biological activity of I–III was determined in relation to the non-pathogenic Mycolicibacterium smegmatis.

Copper(II) and Zinc(II) Complexes with Heterocyclic Acid Anions and 3,5-Dimethylpyrazole: Synthesis, Structure, and Biological Properties

Copper(II) and Zinc(II) Complexes with Heterocyclic Acid Anions and 3,5-Dimethylpyrazole: Synthesis, Structure, and Biological Properties

Synthesis and anti-leukemia activity of phorbol 13,20-diesters and phorbol 12,13,20-triesters

Phorbol esters and their derivatives, such as TPA, have been reported as potential natural antitumor products, with some derivatives entering clinical research for leukemia treatment. In this study, 16 phorbol derivatives were synthesized from phorbol, and their anti-leukemia activity against Jurkat, HL-60, and K562 were tested. The results showed that several derivatives had anti-leukemia activity, with 5B demonstrating the strongest cytotoxic activity against the K562 cell line (IC50 = 0.24 ± 0.04 μM). Based on the IC50 values, a structure-activity relationship was established. When the substituent contained an aromatic group, phorbol derivatives esterified with long-chain organic acids at three reactive hydroxyl groups (C12-OH, C13-OH, and C20-OH) had better activity. When aryl groups were absent from the substituent groups, phorbol derivatives esterified with short-chain organic acids at two hydroxyl groups had better activity. Derivatives esterified with heterocyclic acids, either tri-substituted or di-substituted, showed a significant decrease in cytotoxicity. The mechanism of anti-leukemia activity was explored through flow cytometry, which indicated that phorbol esters inhibited the growth of leukemia cells by inducing apoptosis, leading to cell death. Molecular docking data of compound 5B docking to PKC δC1B suggested that substituent groups should not be too large, and caution should be taken when substituting C20-OH. Overall, these findings provide valuable insights into the design of more effective phorbol esters as anti-leukemia agents, but further research is needed to confirm their safety and efficacy in clinical settings.

Synthesis and characterizations of heterocyclic esters in solvent free condition

A series of different heterocyclic esters were synthesized with a catalyst, sulfuric acid and hydrogen peroxide as a co-catalyst. Mild temperature condition was administered and no other solvent was used. The synthesized esters were recovered and analysed. This esterification successfully produces heterocyclic acids esters in appreciably good yields with high selectivity. Newly synthesized esters were characterized by 1H Nuclear Magnetic Resonance Spectra, Mass spectrometry (MS), Infrared Spectra and Elemental analysis, Carbon, Hydrogen, Nitrogen, Sulphur and Oxygen.

Ionic melting salt imidazole hydrochloride mediated the decarboxylation of (hetero)aromatic carboxylic acids

Imidazole hydrochloride, a hydrochloric acid carrier, was used to mediate the decarboxylation of ortho-para position amino-substituted aromatic acids and nitrogen-containing heterocyclic acids, which gave excellent yields within a short time. In addition, the method can be well adapted to a gram scale, and the imidazole hydrochloride additives can be appropriately recovered for secondary utilization.

Synthesis, Biological Evaluation and Mechanism Studies of C-3 Substituted Nitrogenous Heterocyclic 23-Hydroxybetulinic Acid Derivatives as Anticancer Agents

Synthesis, Biological Evaluation and Mechanism Studies of C-3 Substituted Nitrogenous Heterocyclic 23-Hydroxybetulinic Acid Derivatives as Anticancer Agents

«Soft—hard» strategy to construct a pyrazine sulfonic acid copper(II) supramolecular structure and a study of its fluorescent property

The design and synthesis of functional heterocyclic sulfonic acid polymers would provide much help in studying the coordination behavior, structural optimization, and application of the polymers. In this work, a three-dimensional (3D) supramolecular structure [Na2Cu(P—SO3)4]n (P—SO3H = pyrazine sulfonic acid) is synthesized by a hydrothermal method with the «soft—hard» strategy. The produced polymer is characterized by the elemental analysis, IR spectroscopy, and X-ray crystallography. Crystal diffraction data indicate that the polymer belongs to the P4/ncc space group. Notably, the introduction of a soft alkali metal ion can trigger the specific affinity binding with sulfonate oxygen atoms to give rise to a Na—O-μ4 bridging pattern. The flexible bridging pattern combined with the rigid structure of copper pyrazine sulfonate is likely to be responsible for the production of the final 3D supramolecular structure. Moreover, powder X-ray diffraction data indicated a good phase purity. Thermal stability, Raman features as well as solid-state fluorescent properties are also investigated in detail.

Bis(pyridyl) ancillary ligands and pyrazine sulfonic acid in the synthesis of two Ag(I) supramolecular structures and fluorescent properties of the latter

The coordination behavior of metal ions coordinated with heterocyclic sulfonic acid is of great significance for the construction of functional sulfonate polymers and the exploration of their potential application. In this study, two novel Ag(I)-based supramolecular structures, namely {[Ag2(4,4'-bipy)2][Ag2(P—SO3)4]·H2O}n (1) and {[Ag(dpp)](P—SO3)·H2O}n (2) (4,4'-bipy = 4,4'-bipyridine, dpp = 1,3-di(4-pyridyl)propane, and P—SO3H = pyrazine sulfonic acid) are synthesized using bis(pyridyl) ancillary ligands to assist the P—SO3H main ligand by the solvent evaporation method. The single crystal X-ray diffraction data indicate that the assynthesized polymers belong to P-1 and P21/n space groups, respectively. In particular, the application of bis(pyridyl) ancillary ligands specifically improves the rigidity and coordination ability of pyrazine sulfonate, and then, it combines with the generated weak interaction to further extend the structure to higher dimensions. Powder X-ray diffraction results and related data, including Raman spectra, thermal stability and solid-state fluorescence characterizations, are also discussed.

Synthesis, Characterization, and Comparative Study of Some Heterocyclic Compounds Containing Isoniazid and Nicotinic Acid Hydrazide Moieties

Some new derivatives of six-membered heterocyclic compounds containing isoniazid and nicotinic acid hydrazide fragments have been synthesized according to green procedures with excellent yields. The structures of the synthesized compounds were confirmed by 1H and13C NMR, IR, and mass spectra and elemental analyses. The compounds were screened for their in vitro antibacterial and antifungal activities. The results showed that the isoniazid derivatives are more active than their analogs containng a nicotinic hydrazide moiety.

Synthesis and Applications of β‐Aminoalkylboronic Acid Derivatives

Abstractα‐Aminoalkylboronic acids display a distinct role in medicinal chemistry, and their utility has been demonstrated by the successful commercialization of three drugs: bortezomib, ixazomib, and vaborbactam. Just as α‐aminoalkylboronic acids are a bioisostere of α‐amino acids, β‐aminoalkylboronates are a bona fide bioisostere of β‐amino acids, thus they also hold promising potential in drug discovery. Moreover, β‐aminoalkylboronates are versatile synthetic intermediates that are amenable to many of the established C−B bond derivatization reactions of chiral optically enriched alkylboronates, leading to the stereocontrolled preparation of valued classes of products such as β‐amino alcohols, 1,2‐diamines, and hemiboronic acid heterocycles. In addition, β‐aminoalkylboronates were shown to act as catalysts in certain organic reactions. This review presents an overview of the strengths and limitations of current preparative methods to access β‐aminoalkylboronic acid derivatives stereoselectively with various substitution patterns. Strategically, several disconnections can be exploited to establish both functional groups. Some of the key methods include the classical Matteson asymmetric homologation chemistry, transition metal‐catalyzed aminoboration of alkenes and formal hydroboration of enamine derivatives, nucleophilic additions of boryl‐substituted carbanions onto N‐functionalized imines, borylative ring openings of aziridines, and functionalization of alpha‐boryl aldehydes.magnified image

Alkyl 3-Nitroacrylates in the Reactions with Heterocyclic CH Acids

The reactions of alkyl 3-nitroacrylates with certain heterocyclic CH acids such as 1,3-dimethylpyrimidine-2,4,6(1Н,3Н,5Н)-trione, 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, 4-hydroxy-6-methyl-2H-pyran-2-one, and 4-hydroxy-2H-chromen-2-one occur in the presence of the Rodionov catalyst to form the Michael adducts. The products structure has been confirmed by 1H, 13C{1H}, and 1Н-15N HMBC NMR as well as IR spectroscopy methods.

3-Pyridinylboronic acid normalizes the effects of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in zebrafish embryos

1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson’s disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 μM); MPTP + Low Dose 3-Pyridinylboronic acid (50 μM) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 μM) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.

НЕКОТОРЫЕ СПОСОБЫ СИНТЕЗА АЦЕТИЛЕНОВЫХ КИСЛОТ

The article presents some methods for the synthesis of acetylene mono, dicarbonoaliphatic, aromatic, heterocyclic acids. Among them, some possess antifungal and biological properties. By the interaction of acids or acid chlorides with the corresponding alcohols, esters can be obtained. Their biological properties, as well as some chemical transformations, were studied. Many synthetic acetylenic acids and their derivatives were synthesized mainly by the Grignard reaction and other methods in order to study their physiological activity. Some of them have gained application as a stabilizer of corrosion methods and others.

Photoluminescent report on red light emitting europium(III) complexes with heterocyclic acid

Five luminescent europium (III) carboxylate complexes have been synthesized by using ligand 3-isopropylpyrazole-5-carboxylic acid as primary ligand and 4,4’-dimethyl-2,2’-bipyridyl, 2,2’-bipyridyl, 5,6-dimethyl-1,10-phenanthroline and 1,10-phenanthroline as secondary ligands and characterized through various techniques. These complexes exhibit excellent thermal stability and characteristic europium centered photoemission spectra under the excitation of ultraviolet light. Luminescence decay curves, Judd–Ofelt analysis, internal quantum efficiency and energy transfer mechanism have also been discussed. The color coordinates and color purity are calculated to investigate red emission of the complexes. The study results reveal that these complexes can be potentially used as red light emitting materials in various optoelectronic devices.

Electrochemical Difunctionalization of Alkenes by a Four-Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides.

An electrochemical four-component reaction cascade Mumm rearrangement was developed. It is a rare example of in situ generation of O-acyl isoamides for 1,3-(O→N) acyl transfer. Inexpensive, commercially available arylethylenes, aryl or heterocyclic acids, acetonitrile, and alcohols were used as substrates. A wide range of aryl acids and alcohols were tolerated and provided imides in satisfactory yields. Subsequent hydrolysis of imides could be utilized to synthesize valuable amides and β-amino alcohol derivatives.

Electrochemical Difunctionalization of Alkenes by a Four‐Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides

AbstractAn electrochemical four‐component reaction cascade Mumm rearrangement was developed. It is a rare example of in situ generation of O‐acyl isoamides for 1,3‐(O→N) acyl transfer. Inexpensive, commercially available arylethylenes, aryl or heterocyclic acids, acetonitrile, and alcohols were used as substrates. A wide range of aryl acids and alcohols were tolerated and provided imides in satisfactory yields. Subsequent hydrolysis of imides could be utilized to synthesize valuable amides and β‐amino alcohol derivatives.

Synthesis of some new N3 substituted 5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridin-2-ones as potential biologically active compounds

Condensed bicyclic systems with thiazolidine core being annulated to pyridine one occupy prominent place in medicinal chemistry because of their broad spectrum of pharmacological activities. So, the synthesis of new N3 substitutes thiazolo[4,5-b]pyridines is relevant with prospect of studying biological activity of the obtained substances.Aim. Expanding the synthetic potential of thiazolo[4,5-b]pyridines, the study of reactivity and synthesis of new N3 substituted 5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridin-2-one derivatives.Materials and methods. Methods of organic synthesis; Physical and physical-chemical methods of analysis of organic compounds (1H NMR spectroscopy, elemental analysis). Results. Changes were made in the main heterocycle at position N3 in order to obtain new thiazolo[4,5-b]pyridines. It turned out that the combination of the reaction of cyanethylation and acid hydrolysis is an effective method of the synthesis of inaccessible 3-(5-hydroxy-7-methyl-2-oxo-thiazolo[4,5-b]pyridin-3-yl)-propionic acid. It helped to obtain a group of amides of this heterocyclic acid as perspective biologically active compounds. The structure of all synthesized compounds was confirmed by the 1H NMR spectroscopy and the data of elemental analysis.Conclusions. As a result of the structural modification of 5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridine-2-one at position N3, a series of new thiazolo[4,5-b]pyridine-2-ones were synthesized. Pharmacological screening of the obtained thiazolo[4,5-b]pyridines was carried out. We continue to research different activities and chemical transformation of these substances with the prospect of studying biological activities.