Letters in Organic Chemistry - Volume 20, Issue 6, 2023

A base-promoted cascade reaction of α-ketoester with benzylidene-malononitrile was developed under mild reaction conditions, which enabled the synthesis of polyfunctionalized 2-amino- 3-cyano-4H-pyrans containing ester motifs at 6-position with good to excellent yields. These transformations not only construct various polyfunctionalized 4H-pyrans, which add a new member to the family of 4H-pyrans, but also provide an efficient approach for the synthesis of fully substituted 4Hpyran derivatives.

Influenza A viruses have caused worldwide epidemics and pandemics by reassortment and generation of drug-resistant mutants, which leads to an urgent need to develop novel antivirals. In this study, a series of sulfonyl piperazine nucleozin derivatives were designed and synthesized, and their in vitro anti-influenza activity was evaluated. Many of these compounds exhibited moderate to good anti-influenza activity against influenza A. Among these, 6d, 6g, 6h, 6i, and 6j exhibited better activity than ribavirin. 2,3-dichlorobenzene substituted analogue 6i displayed the most remarkable in vitro activity against Influenza A. All the derivatives show no obvious cellular growth inhibition against MDCK cells. This study reported a new series of nucleoprotein inhibitors with a good selectivity window and potential for further development as novel anti-influenza agents.

Hydroxy-substituted anthraquinones are among the most important derivatives in organic synthesis. The attractive biological properties of these compounds are relevant to many therapeutic areas that are of use in clinical applications. In this study synthesized several amino-substituted anthraquinones were synthesized from 1,4-dihydroxyanthraquinone using a modified Marschalk reaction. Moreover, 1,4,5-trihydroxyanthraquinone was synthesized from anacardic acid, an agro-waste from the cashew industry. The in vitro screening of the compounds against Trypanosoma brucei parasites revealed noteworthy activity with reasonable selectivity against human cell lines. A molecular docking study was performed to analyze the synthesized compounds' modes of interaction to the trypanothione reductase's active site. Visual inspections examined the docked poses, and test compounds displayed a good binding affinity with the receptor protein. This in vitro/ molecular docking evaluation suggests that substituted 1,4-dihydroxyanthraquinone derivative can be promising starting structures in the search for active drugs against trypanosomiasis.

Background: In order to synthesize benzoxazin-4 (3H) -one derivatives, a new inorganic- organic super-magnetic nano-hybrid (γ-Fe2O3@ CPTMS-DETA @SO3H) nanocatalyst of the modified sulfuric acid represents a green and efficient catalyst to perform a three-component condensation reaction between various acyl chlorides, anthranilic acid and acetic anhydride (as cyclization agent), in one-pot and solvent-free conditions under microwave irradiation (4a-q). Introduction: In recent years, one of the most important subjects in synthetic organic chemistry has been green synthesis, which has applied environmentally friendly and efficient methods to synthesize biological derivatives. The use of catalysts has significant advantages, including simple separation and preparation, chemical and thermal stability, and eco-friendly nature and their features such as reusability, low cost, high efficiency and easy operation. Therefore, the mechanism is performed by a non-toxic organic catalyst that uses the chemical reactants and the least energy in accordance based on the least waste and green chemistry. Methods: Sequential addition and one-pot methods were applied to produce benzoxazinone derivatives. In the sequential addition approach, the reaction was begun by adding anthranilic acid and acetic anhydride to the reaction vessel under microwave irradiation and continued by adding γ-Fe2O3@ CPTMS-DETA @SO3H as super-magnetic nano-hybrid recyclable green catalysts and the desired acyl chlorides. Results: The main objective of this project was to synthesize benzoxazin-4 (3H) -one derivatives in the presence of super-paramagnetic organic-inorganic nanohybrid particles based on improved sulfonic acid (γ-Fe2O3 @ SiO2 - DETA @ SO3H) as an efficient recyclable heterogeneous catalyst. Conclusion: This paramagnetic nano-organocatalyst was characterized by EDX, VSM, TGA, FESEM, FT-IR, and XRD. Advantages of this catalyst include easy preparation, clear and easy operation, short reaction time (15–30 min), as well as without the use of toxic catalysts. In addition, the catalyst can be separated from the reaction solution using an external magnet by magnetic decantation; it can be recycled up to six times without reducing its activity.

An effective organocatalyzed ipso-hydroxylation of arylboronic acids for the preparation of phenol derivatives has been demonstrated. The elucidated phenomenon relies on the catalytic performance of 3-nitropyridine under the influence of sub-stoichiometric quantities of KO^tBu employing aerobic conditions in DMSO solvent. This method excludes the excess usage of oxidizing agents and bases by providing a user-friendly synthetic tool for the preparation of phenols. It was acclaimed that the 3-nitropyridine acts as an oxygen transferring agent from in situ generated hydrogen peroxide to boronic acid derivatives to furnish the desired molecules. The required hydrogen peroxide was in situ generated from aerial oxygen by the KO^tBu-mediated single electron transfer process. The described process is applicable to a variety of arylboronic acids for the preparation of phenols in good yields with considerable resistance of functional moiety.

Herein, we have reported an efficient synthesis of 2-aryl benzimidazoles by reacting ophenylenediamines and substituting aromatic aldehydes using SO4²⁻/ZrO2-TiO2 as a heterogeneous catalyst. This methodology is straightforward to obtain 2-aryl benzimidazoles with good to excellent yields. It has been performed in ethanol as a green solvent. The reported protocol has some advantages such as a safe and reusable heterogeneous catalyst, without any need for column chromatography to obtain desired products. The catalyst can be recovered for up to five catalytic cycles without significant loss in the catalytic activity.

Valorization of agricultural waste to produce value-added products such as nanocellulose is important in bringing sustainable development and reduce our dependence on petroleumbased products which are harmful to our environment. The present work is carried out to investigate the potential of the pseudostems from the wild Musa spp. as a novel sustainable source of cellulose nanocrystal (CNCs). TEMPO-mediated oxidation and ultrasonication was followed in isolation of CNCs. The CNCs were characterized by various physicochemical parameters such as FTIR, TEM, Zeta potential, degree of oxidation, swelling and water retention value. TGA studies was performed to evaluate the thermal stability and percent crystallinity was determined by XRD spectroscopy. The final carboxylated CNC (cCNC) gel contains 5.56% w/w solid CNC exhibiting degree of oxidation of 34.91%. The CNC also showed high water retention value exhibiting ionic sensitivity to NaCl. The zeta potential value was determined to be -50.3 mV indicating its stability and particle size of the cCNC was less than 200 nm. The percent crystallinity was found to be 66.18% and TGA analysis showed the reduced thermal stability of the cCNCs. Carboxylated CNC was successfully isolated from the wild banana pseudostem following TEMPOoxidation method. Ultrasonication of the cCNC resulted in the formation of cCNCs with mostly spherical in shapes and the results from analysis indicate that the wild banana pseudostem could be a potential sustainable source of cellulose nanocrystals.

Visible light has come to the fore in organic chemistry as a cheap and readily available energy source. Energy transfer reactions represent the future directions for the development of practical and scalable industrial reactions with several environmental benefits. A facile, economic, and visible light (CFL) induced synthesis of perimidines has been established through a cyclo-condensation reaction of 1,8-diaminonaphthalene and aryl aldehydes with excellent yields (87-100%) in a short span of time. The present method has several merits a highly efficient, greener, high atom economy, no need of external heating and other instrumental setups, no need for a catalyst, and no tedious purification process.

Karanjin (1) is a natural furanoflavonol derivative isolated from seeds of Pongamia pinnata (L.) Pierre. In this paper, we have accomplished a concise total synthesis of karanjin (1) as well as its natural analogues pongapinnol D (2), 3-hydroxy-6-methoxy-2-phenyl-4H-furo[2,3-h]-1-benzopyran- 4-one (3) and 3,6-dimethoxy-2-phenyl-4H-furo[2,3-h]chromen-4-one (4). One-pot aerobic oxidation was the key step to afford the flavonol framework under mild conditions. The anti-inflammatory properties of synthesized 1–4 were determined against NO production in the LPS-stimulated RAW264.7 cells.

In the present study, we have introduced an efficient solvent-free protocol for the synthesis of glycosyl annulated phosphorylated/thiophosphorylated 1,2,3-triazole derivatives using reusable CuFe2O4 magnetic nanoparticles as a heterogeneous catalyst with the protocols of popular click chemistry approach. Quantum chemical calculations of all the reactants and products have been calculated using density functional theory with Spartan-18 software. In addition, the molecular docking studies of all the glycosyl annulated phosphorylated/thiophosphorylated 1,2,3- triazole derivatives have been studied as effective fungicides against CaCYP51 (PDB ID 5EQB), protein of P. infestans effector target site (PDB ID: 2NAR), and SsCYP51(PDB code: 6CR2) using Autodock Vina and Discovery Studio software. Among the three different proteins, the binding energies of the compounds (5a-d) with CaCYP51 (PDB ID 5EQB) have shown better results in the range of 7.0 to 7.4 kcal/mol. Hence, these compounds may be used as strong fungicides for the inhibition of CaCYP51 (PDB ID 5EQB). In conclusion, the synthesized compounds may be better useful in agrochemical applications as vital fungicides.

The aim of this study is to isolate and identify new chemical constituents from Cordyline fruticosa (L.) A. Chev. growing in Vietnam. Cordyline fruticosa (L.) A. Chev. (Synonym: Cordyline terminalis L. Kunth), belongs to the Asparagaceae family, is one of the popular plants in folk medicine. This plant has been used to treat various diseases, such as sore throat, neck pain, bloody urine, kidney diseases, headache, infections of mammary glands, and inflammation in the digestive tract. Previous study on the leaves of C. fruticosa (L.) A. Chev. reported the presence of cholestane glycosides with cytotoxic activity. The leaves of Cordyline fruticosa (L.) A. Chev. were provided by a flower shop in Thai Nguyen city, Vietnam in 2021 (21°35'53" N, 105°50'17" E). The extraction was performed by the ultrasound-assisted method using the solvent EtOH/H2O. The crude extract was chromatographed on silica gel to yield one compound. The structure elucidation of isolated compound was determined by spectroscopic analysis 1D and 2D NMR, and mass spectroscopy (HR-ESI-MS in positive mode). A new steroidal saponin was isolated from the leaves of Cordyline fruticosa (L.) A. Chev. The structure of compound was determined as 26-O-β-D-glucopyranosyl-furosta-5,(25)27- diene-1β,3β,22α,26-tetrol-1-O-β-D-glucopyranoside. Phytochemical study on the leaves of Cordyline fruticosa (L.) A. Chev. lead to the isolation and elucidation of one new steroidal saponin. Previous investigation on species of Cordyline genus revealed the presence of steroidal saponins, so this study has a significant benefit to complete the chemotaxonomic data about saponins from genus Cordyline and thus Asparagaceae family. The biological test of this compound should be further carried out in the next study.