Search Results (16)

We investigated the reactivity of a new sulfur-containing compound derived from Meldrum’s acid and phenyl isothiocyanate, triethylammonium 1-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(phenylamino)methanethiolate. Under aminomethylation conditions (using aqueous formaldehyde and primary amines), this compound undergoes a double aminomethylation to form novel 1,3,5-thiadiazine derivatives. These new compounds, 2,2-dimethyl-5-(3-phenyl-1,3,5-thiadiazinan-2-ylidene)-1,3-dioxane-4,6-diones, were previously unknown. This study also explores some properties of the synthesized 1,3,5-thiadiazines. Full article

The synthesis and application of new chiral amino acids (AAs) and peptides derived thereof is a research topic of major importance. The introduction of γ-AA as building blocks are useful for the development of original chiral small molecules and heterocycles, enabling the exploration of 3D chemical space in search of selectivity in biological properties. 4.5-Dihydro-2H-pyridazin-3-ones (DHPDOs) are 6-membered aza-heterocycles considered as masked γ-AA analogues. We herein report on the synthesis of various a-monosubstituted DHPDOs as platform-molecules using Meldrum’s acid chemistry and the a-functionalization approach upon the asymmetric Michael addition using the Phase-Transfer Catalysis (PTC). Full article

Free radicals and oxidants may cause various damages both to the lifeworld and different products. A typical solution for the prophylaxis of oxidation-caused conditions is the usage of various antioxidants. Among them, various classes are found—polyphenols, conjugated polyalkenes, and some sulfur and nitrogen derivatives. Regarding the active site in the molecules, a widely discussed group of compounds are 1,3-dicarbonyl compounds. Among them are natural (e.g., curcumin and pulvinic acids) and synthetic (e.g., 4-hydroxy coumarins, substituted Meldrum’s acids) compounds. Herein, information about various compounds containing the 1,3-dicarbonyl moiety is covered, and their antiradical and antioxidant activity, depending on the structure, is discussed. Full article

The structural, photophysical, and vibrational properties of a new hydroxyphenylamino Meldrum’s acid derivative, 3-((2-hydroxyphenylamino)methylene)-1,5-dioxaspiro[5.5]undecane-2,4-dione (HMD), were studied. The comparison of experimental and theoretical vibrational spectra can help understand basic vibration patterns and provides a better interpretation of IR spectra. The UV–Vis spectrum of HMD was computed using density functional theory (DFT)/B3LYP/6-311 G(d,p) basis set in the gas state, and the maximum wavelength was in accord with the experimental data. The molecular electrostatic potential (MEP) and Hirshfeld surface analysis confirmed O(1)–H(1A)···O(2) intermolecular hydrogen bonds in the HMD molecule. The natural bond orbital (NBO) analysis provided delocalizing interactions between π→π* orbitals and n→σ*/π* charge transfer transitions. Finally, the thermal gravimetric (TG)/differential scanning calorimeter (DSC) and the non-linear optical (NLO) properties of HMD were also reported. Full article

In the presented study, eight novel Meldrum’s acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum’s acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 μM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 μM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best E_b was noted for the topoisomerase II beta-LYS482-3i cluster. Full article

The Michael addition reaction between dithiomalondianilide (N,N′-diphenyldithiomalondiamide) and arylmethylidene Meldrum’s acids, accompanied by subsequent heterocyclization, was investigated along with factors affecting the mixture composition of the obtained products. The plausible mechanism includes the formation of stable Michael adducts which, under the studied conditions, undergo further transformations to yield corresponding N-methylmorpholinium 4-aryl-6-oxo-3-(N-phenylthio-carbamoyl)-1,4,5,6-tetrahydropyridin-2-thiolates and their oxidation derivatives, 4,5-dihydro-3H-[1,2]dithiolo[3,4-b]pyridin-6(7H)-ones. The structure of one such product, N-methylmorpholinium 2,2-dimethyl-5-(1-(2-nitrophenyl)-3-(phenylamino)-2-(N-phenylthiocarbamoyl)-3-thioxopropyl)-4-oxo-4H-1,3-dioxin-6-olate, was confirmed via X-ray crystallography. Full article

A simple and efficient protocol for the synthesis of the previously unknown 2-(2-(4-methoxyphenyl)furo[3,2-h]quinolin-3-yl)acetic acid was elaborated. The suggested method is based on the telescoped multicomponent reaction of 8-hydroxyquinoline, 4-methylglyoxal, and Meldrum’s acid. The studied process includes the initial interaction of the starting compounds in MeCN followed by intramolecular cyclization to the target product in refluxing acetic acid. The advantage of this approach is the application of readily available starting materials, atom economy, and a simple work-up procedure. The structure of the synthesized furylacetic acid derivative was proven by ¹H, ¹³C, 2D-NMR, IR spectroscopy, and high-resolution mass spectrometry. Full article

Activated 2-furfural gives intense color formation when reacted with amines, due to a ring opening reaction cascade that furnishes a conjugated molecular system. Unique colorimetric characteristic of this reaction makes it an interesting candidate for developing chemosensors operating in visible range. Among many activated 2-furfural derivatives, Meldrum’s acid furfural conjugate (MAFC) recently gained significant interest as colorimetric chemosensor. MAFC has been explored as selective chemosensor for detecting amines in solution, secondary amines on polymer surfaces and even nitrogen rich amino acids (AA) in aqueous solution. In this work, the pH dependency of MAFC-AA reaction is explored. It was found that proline gives an exceptionally fast colored reaction at pH 11, whereas at other pHs, no naked eye color product formation was observed. The reaction sequence including ring opening reaction upon nucleophilic addition of cyclic amine of proline resulting in a conjugated triene was confirmed by NMR titrations. The highly pH dependent reaction can e.g., potentially be used to detect proline presence in biological samples. An even more intense color formation takes place in the reaction of natural proline derivative 4-hydroxyproline. The detection limit of proline and 4-hydroxyproline with MAFC solution was found to be 11 µM and 6 µM respectively. Full article

In continuation with our research in the use of enols in multicomponent reactions with isocyanides (IMCR), for the first time we have used amide-stabilized enols as the acid component in enol-Ugi reactions. Thus, the reaction of 2-(hydroxy(phenylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione with aldehydes, amines and isocyanides provides the expected enamine adducts. On the other hand, the use of analogous Meldrum’s acid-derived enols permits the synthesis of triamides by a five-component process with the participation of a molecule of solvent. These results confirm the great potential of the enol-Ugi reaction for the preparation of a wide variety of structures containing a peptidomimetic scaffolds. Full article

A simple one-pot approach was developed for the synthesis of furan-2(5H)-one derivative containing indole fragments. This method includes the telescoped multicomponent reaction of indole, 4-methoxyphenylglyoxal, and Meldrum’s acid. The synthetic utility of the prepared furan-2(5H)-one was demonstrated by condensation with 4-methoxybenzaldehyde. The advantages of this method include the employment of readily accessible starting materials, atom economy, process simplicity, and the easy isolation of the target products. The structure of the synthesized furanones was confirmed by ¹H and ¹³C-NMR spectroscopy and high-resolution mass spectrometry with electrospray ionization (ESI-HRMS). Full article

Faced with the ban of some organic UV filters such as octinoxate or avobenzone, especially in Hawaii, it became essential to offer new alternatives that are both renewable and safe for humans and the environment. In this context, a class of bio-based molecules displaying interesting UV filter properties and great (photo)stability has been developed from Meldrum’s acid and bio-based and synthetic p-hydroxycinnamic acids, furans and pyrroles. Moreover, p-hydroxycinnamic acid-based Meldrum’s derivatives possess valuable secondary activities sought by the cosmetic industry such as antioxidant and anti-tyrosinase properties. The evaluation of the properties of mixture of judiciously chosen Meldrum’s acid derivatives highlighted the possibility to modulate secondary activity while maintaining excellent UV protection. Meldrum’s acid derivatives are not only competitive when benchmarked against organic filters currently on the market (i.e., avobenzone), but they also do not exhibit any endocrine disruption activity. Full article

Photoluminescent divinylbipyrroles were synthesized from 3,3′,4,4′-tetraetyl-2,2′-bipyrrole-5,5′-dicarboxaldehyde and activated methylene compounds via aldol condensation. For mechanistic clarity, molecular structures of Meldrum’s acid- and 1,3-dimethylbarbituric acid-derived divinylbipyrroles were determined by single-crystal X-ray diffraction. Photoluminescent properties of the synthesized divinylbipyrroles in dichloromethane were found to be dependent on the presence of electron withdrawing groups at the vinylic terminal. The divinylbipyrroles derived from malononitrile, Meldrum’s acid, and 1,3-dimethylbarbituric acid showed fluorescent peaks at 553, 576, and 602 nm respectively. Computational studies indicated that the alkyl substituents on the bipyrrole 3 and 3′ positions increased energy level of the highest occupied molecular orbital (HOMO) compared to the unsubstituted derivatives and provided rationale for the bathochromic shift of the ultraviolet-visible (UV-Vis) spectra compared to the previously reported analogs. Full article

Alzheimer’s disease (AD) lies in the category of those diseases which are still posing challenges to medicinal chemists, and the search for super-effective drugs for the treatment of AD is a work in progress. The inhibition of cholinesterase is considered a viable strategy to enhance the level of acetylcholine in the brain. The C-5 substituted derivative of Meldrum’s acid was synthesized and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activity. The simple and unique structure of synthesized derivative 3 was found to be good for the dual inhibition of both enzymes (AChE and BChE). 2,2-Dimethyl-5-(([2-(trifluoromethyl) phenyl]amino)methylidene)-1,3-dioxane-4,6-dione (3) showed significant inhibition against AChE, with an IC₅₀ value of 1.13 ± 0.03 µ M (Standard Neostigmine 22.2 ± 3.2 µM), and moderate inhibition against BChE, with an IC₅₀ value of 2.12 ± 1.22 µM (Standard Neostigmine 49.6 ± 6.11 µM). The structural insights reveal that compound 3 possesses intriguing reactive groups, which can potentially evoke the non-covalent interactions and possibly assist by binding in the active site of the target protein. Docking simulations revealed that the compound 3 showed binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained, as the best docked poses showed important binding features mostly based on interactions due to oxygen atoms and the aromatic moieties of the compound. The docking computations coupled with the experimental findings ascertained that the compound 3 can serve as a scaffold for the dual inhibitors of the human acetylcholine esterases. Full article

A mild and efficient synthesis of pyrazolo[3,4-b]pyridine-6(7H)-one derivatives via a three-component reaction of an aldehyde, Meldrum’s acid and 3-methyl-1H-pyrazol-5-amine using recyclable polyethylene glycol (PEG)-400 as a reaction medium is described. This method has the advantages of accessible starting materials, good yields, mild reaction conditions and begin environmentally friendly. Full article