Current Organic Chemistry - Volume 27, Issue 19, 2023

Functionalized 3-amino-2-azetidinones are important heterocyclic systems which can easily be transformed into functionally decorated heterocycles using β-lactam synthon protocol. The different synthetic methods have been explored for the transformation of functionalized 3-amino-2-azetidiones to various heterocyclic molecules, such as imidazolidin-2-ones, piperazines, hydantoins, 4-oxo-1H-pyrroles, 1,4-benzodiazepin-2-ones, amino pyrrolidine-2- carboxylates etc., and β-lactam- based conjugates having diverse biological activities, such as anti-malarial activity, anti-tuberculosis, anti-trichomonas activity etc. The present review article summarizes the various reports on the synthetic transformation of functionalized 3-amino-2- azetidinones for the synthesis of a variety of heterocyclic systems.

Nowadays, fossil fuels represent the main energy source. According to the BP Statistical Review of World Energy report, in 2021, global energy consumption amounted to 595.15 EJ of which 82% was generated from natural gas, oil and coal. The energy consumption growth, rapid depletion of fossil fuels and increasing pressure on the environment threaten the continued sustainability of the global energy system. In this context, renewable energy sources (RES), which now account for 6.7% are attracting increasing attention. The key obstacles to the introduction of RES (solar, wind geothermal, etc.) are their nonstationarity due to seasonality, meteorology and differences in geoclimatic conditions. In this regard, an important role is played by the development of technologies for efficient storage and transportation of renewable energy to consumers. One of the most promising storage technologies is the processing of renewable energy into hydrogen, which, due to the high mass energy intensity (120 MJkg-1) and environmental friendliness, can be considered a promising energy carrier. Nevertheless, the widespread use of hydrogen as a fuel is limited due to the low volumetric energy density and high explosiveness. Thus, along with the development of technologies for processing renewable energy sources into hydrogen (e.g., electrolysis), a large number of studies are focused on the development of technologies for storage and transportation. This study provides a brief overview of the state of the art of these technologies, with a focus on technology based on the use of liquid organic hydrogen carriers (LOHCs).

The Purine moiety is regarded as the ubiquitous nitrogen-containing heterocycle in nature and is recognized as a privileged scaffold in medicinal chemistry. Moreover, the purine derivatives are heterocyclic aromatic compounds consisting of conjoined pyrimidine and imidazole moieties. Purine derivatives are involved in various metabolic processes as cofactors associated with a wide variety of enzymes and receptors. Therefore, many synthetic ways to obtain purine derivatives were developed using different reagents such as pyrimidine, imidazole, and some acyclic precursors. This article review focuses on the synthetic methodologies of purine derivatives from its first synthesis in the 19th century to this last decade and also reports a variety of proven pharmacological applications for the purine derivatives. This review offers a panoply of synthetic routes that medicinal and organic chemistry researchers can use in the preparation and design of new purine derivatives.

Cytochrome P450 3A4, the most abundant form of isoenzyme, in combination with several other isoforms, metabolizes lignocaine into mono-ethylglycine xylidide (MEGX) and glycylxylidide (GX), through N-dealkylation, ring hydroxylation, amide cleavage, and conjugation process which contribute the toxic effects. Inspiring by the rationality, functional approaches, and predictable facts lay by the emerging research groups, we were unquestionably fascinated by the rational development of novel lignocaine and etidocaine compounds, which are highly metabolically stable by applying non-classical bioisosteric principles. Distinctively, we have investigated the efficacy of 1,4- disubstituted-1,2,3-triazoles as metabolically stable trans-amide bond mimics. The 1,2,3- triazoles have been described in the literature as amide bond bioisosteres, which are analogous in stipulations of size, planarity, hydrogen bonding properties, and dipole moment. The systematic replacement of the single amide bonds by the 1,2,3-triazole heterocycle in the backbone of the peptide, often termed a “triazole scan,” provided several stabilized analogs with marked improved in-vivo local anesthetic properties. The analogs were synthesized using azide-alkyne cycloaddition. The 2a-b was coupled with aromatic and aliphatic alkynes using click chemistry in the presence of copper sulfate pentahydrate and L-sodium ascorbate in a Fritsch ball mill under solvent-free conditions at 300 rpm, furnishing the conjugates 4a-n in 80- 85% yields. The study perceptively opened new avenues of systematic replacement of the single amide bonds by the 1,2,3-triazole heterocycle in the backbone of the peptide, thereby providing several stabilized analogs with marked improved in-vivo local anesthetic properties. The best active candidates 4a, 4b and 4g produced analogous local anesthetic activity with that of the lignocaine.

5-aminolevulinic acid (5-ALA) applications in medicine and agriculture face the challenge of stability. In aqueous solutions, concentration, pH, and temperature have an effect on the loss of activity. Computational chemistry helps to determine tautomerization, formation of derivatives and the stability, in different conditions, in a short time and reducing the cost of analysis. This work aimed to model the 5-ALA molecule and its tautomers in aqueous solution, determine its pKa and molar fractions at different pH, determine its thermodynamic and kinetic parameters, and predict the degree of dimerization under different conditions. Gaussian 16 program, Density Functional Theory, and the M05-2X functional were used to obtain the stationary state frequencies. From the difference in Gibbs free energy (ΔGs) between each acid/base conjugate, pKa values and molar fractions at different pH's were determined. Equilibrium constants were calculated from the ΔGr at different temperatures. Using data from the literature, the activation energy was optimized and the rate constants were obtained. A model was obtained to approximate the half-life, t0.5, and shelf-life, t0.9, values for 5-ALA solutions. pKa values obtained, 4.40 and 7.87, coincide with the potentiometric determinations reported in the literature. The thermodynamic and kinetics parameters calculated in this study correctly predict the percentage of 5-ALA dimerization at concentrations ≤ 0.075M (1.25%) and 15°C-50°C. This work integrates quantum chemistry and literature data to generate a model for the degree of decomposition of 5-ALA at different pH, temperature and concentration. It will be useful in applications in medicine, agriculture and other fields.

Rhodium catalysts for hydroformylation of aryl alkenes generally promote the formation of branched aldehydes. Here, we have demonstrated that by using a single rhodium catalyst containing a diphosphoramidite ligand derived from BINOL, it is possible to achieve the inversion of regioselectivity in the hydroformylation of aryl alkenes simply by reducing the syngas pressure or, alternatively, increasing the reaction temperature. Indeed, the hydroformylation of styrene carried out at 20 bar and 50°C resulted in 72% of 2- phenylpropanal, while at atmospheric pressure, 71% of 3-phenylpropanal was obtained. A similar linear selectivity (72-74%) was observed when the hydroformylation of styrene, pmethylstyrene, and p-methoxystyrene was performed at 10 bar and higher temperature (80°C). The regioselectivity of the hydroformylation of trans-β-methylstyrene under mild conditions (80°C, 10-20 bar) was also strongly influenced by the syngas pressure. The results of this study show that it is possible to reverse the selectivity of aryl alkenes hydroformylation with a single catalyst by simply exploring the reaction conditions. In this paper, we have shown that the inversion of the regioselectivity in the hydroformylation of aryl alkenes can be achieved using a single rhodium catalyst containing a BINOL-derived diphosphoramidite ligand by reducing the syngas pressure or, alternatively, increasing the reaction temperature.

In ethanolic piperidine solution, the interaction of 6-bromonaphthalen-2-ol (1) with α- cyano-p-chlorocinnamonitrile (2a) or ethyl α-cyano-p-chlorocinnamate (2b) yielded 4Hnaphtho[ 2,1-b]pyran-3-carbonitrile (3a) and 4H-naphtho[2,1-b]pyran-3-carboxylate (3b). The naphthopyran derivatives (3a, b) reacted with electrophilic reagents afforded naphthopyranopyrimidines and naphthopyrano-triazolopyrimidine derivatives. The structures of the newly synthesized compounds are confirmed through spectral analysis using NMR, IR, and MS spectroscopy. The anticancer efficacy of all compounds was investigated against three cancer cell lines: MCF- 7, HeLa, and PC-3, along with a molecular docking study.

The oxidation of polycyclic aromatic hydrocarbons (PAH) with mono-oxygen donors such as iodosylbenzene, hydrogen peroxide and tert-butyl hydroperoxide in the presence of selected 5,10,15-triarylmanganese( III) corroles as catalysts were examined under different reaction conditions. The effect of reaction conditions on triaryl-manganese(III) corroles catalysts and oxidants is discussed. It was observed that in a solvent system consisting of a mixture of dichloromethane and acetonitrile, the oxidation of anthracene with tertbutyl hydroperoxide catalysed by tri(aryl)manganese(III)corroles worked better than with hydrogen peroxide or iodosylbenzene as the oxidants. The oxidation of anthracene with hydroxo-manganese(IV)corroles was also examined in organic solvents under mild conditions. UV-Vis and other spectroscopic data were used to determine the oxidative mechanism for the oxidation of anthracene and other polycyclic aromatic hydrocarbons with mono-oxygen donors catalysed by triaryl-manganese(III)corroles.