Oxazine Derivatives Research Articles

Lead(II) Schiff Base Complexes: Design, Synthesis, Theoretical, Antibacterial and Docking Studies

This study presented the bioactive lead(II) compounds of oxazine and thiazine Schiff-bases using NMR (1H, 13C), FT-infrared spectroscopy, UV-visible, molar conductance, elemental analysis and molecular weight. The molecular parameters e.g. bond length, bond angle, HOMO/LUMO energy gap and softness/hardness was calculated by DFT-B3LYP/Lanl2dz basis set. According to the spectral data, the Schiff-base coordinated to the lead atom in bidentate mode. A theoretical DFT computational investigation was conducted to supplement the experimental data. The antibacterial activity of lead complexes against E. coli (–) and S. aureus (+) bacteria was determined by disc-diffusion method. Lead complexes of thiazine derivatives are more active than oxazine derivatives. In order to better understand the molecular interaction and binding mode of the drugs, a molecular docking study has been carried out on the protein 3q8u (NDK) from S. aureus. A docking investigation with the NDK protein (S. aureus) revealed that compound 1h has the highest binding affinity (-8.18 Kcal/mol) among the eight ligands (1a-h).

Molecular Docking and DFT Study of Synthesized Oxazine Derivatives

Molecular Docking and DFT Study of Synthesized Oxazine Derivatives

FNAOSiPPEA[]/Zn(II) as a Bifunctional Lewis Acid/ Bronsted Base Heterogeneous Magnetic Nanocatalyst Based on Nano‐Almond Shell for Synthesis of Naphtho[1,3]oxazine Derivatives**

AbstractFe3O4@nano‐almondshell@OSi(CH2)3/2‐(1‐piperazinyl)ethylamine/Zn(II) abbreviated (FNAOSiPPEA/Zn(II)) as a Lewis acid/ Bronsted base double‐layer magnetic nano‐catalyst was prepared by immobilization of Zn‐diamine complex on functionalized nano‐almondshell coated Fe3O4 NPs. The properties of the FNAOSiPPEA/Zn(II) nano‐catalyst were identified by the of FT‐IR, FESEM, TGA, EDS‐MAP, XRD, VSM, and BET techniques. The catalytic performance of FNAOSiPPEA/Zn(II) as a strong and effective Lewis acid for the synthesis of 2‐aryl(alkyl)‐2,3‐dihydro‐1H‐naphtho[1,2‐e][1,3]oxazine derivatives, abbreviated ADNO, was evaluated. A three‐component reaction between formaldehyde, primary amines, and phenolic compounds such as β‐naphthol, α‐naphthol, phenol, and hydroquinone was occurred in this protocol. FNAOSiPPEA/Zn(II) can be reused four times with a slight loss of catalytic activity.

Synthesis of new coumarin[1,3]oxazine derivatives of 7-hydroxy-6-isobornyl-4-methylcoumarin and their antioxidant activity.

In this work, we synthesized a series of new 9,10-dihydro-2H,8H-chromeno[8,7e][1,3]oxazine-2-on derivatives which incorporate isobornylcoumarin and 1,3-oxazine moieties. A structure-antioxidant activity relationship was analyzed. A comparative evaluation of their radical scavenging activity, antioxidant and membrane-protective properties was carried out in test with DPPH, as well as on the models of Fe2+ /ascorbate-initiated lipid peroxidation and oxidative hemolysis of mammalian red blood cells. The results suggest that all the obtained coumarin[1,3]oxazine derivatives of 7-hydroxy-6-isobornyl-4-methylcoumarin are capable of exhibiting antioxidant activity in various model systems. Compound 7 with a phenyl fragment, combining high radical scavenging activity and the ability to inhibit Fe2+ /ascorbate-initiated peroxidation of animal lipids in a heterogeneous environment, also proved to be the most effective membrane protector and antioxidant in the model of H2 O2 -induced erythrocyte hemolysis.

IN SILICO STUDIES OF N-(PHENYL SUBSTITUTED) 2-([PHENYL SUBSTITUTED) METHYLIDENE] AMINO)-N,4- DIPHENYL-6H-1,3-OXAZIN-6-AMINE DERIVATIVES AS POTENTIAL ANTIBACTERIAL AGENTS

Resistance to bacteria is a growing threat to human health worldwide. The rate of discovery of new antibacterial is far outshined by the rate at which resistance is spreading. Therefore, there remains a pressing need for the development of new antibacterial drugs. Recent alarm estimates that deaths due to antimicrobial resistance may increase from 700,000 million lives annually by 2050. Glucosamine-6-phosphate (GlcN-6-P) synthase represents an interesting protein target because it plays an essential role in the protection of cell wall. The primary aim and objective of this study is to identify lead molecules as promising antibacterial agents by inhibiting Glucosamine-6-phosphate (GlcN-6-P) synthase enzyme. Autodock 4. 2, the effective tool for exploring the binding affinity of small molecule to enzyme target was used to study the interactions between the oxazine derivatives and the GlcN-6-P synthase binding site. The ligands were optimized for improving their efficacy and safety. Lead optimization was performed using Molinspiration server and the ligands were optimized for evaluating their oral bioavailability. With Glucosamine 6 phosphate synthase receptor, the binding energy was found to be best for 5 compounds SZ-3 (-5.27 kcal/mol), SZ-4 (-6.02 kcal/mol), SZ-5 (-5.35 kcal/mol), SZ-8 (-5.62kcal/mol), SZ-10 (-5.29 kcal/mol) when compared to the standard ligand, Ciprofloxacin (-5.09 kcal/mol) and were interacting well with the key residues TYR 304, GLU 438, LEU 484. Docking study strongly enhanced the activity of oxazine derivatives as new discovered hits.

Synthesis of new bimetallic phosphate (Al/Ag3PO4) and study for its Catalytic performance in the synthesis of 1,2-dihydro-l-phenyl-3H-naphth [1,2-e]-[1,3] oxazin-3-one derivatives

<p>This work aims to prepare a new bimetallic phosphate catalyst using a new simple and effective method. This new catalyst was ready for the first time by a modification of Triple Super Phosphate (TSP) fertilizer with silver sulfate (AgSO<sub>4</sub>), followed by the impregnation of the aluminum atoms using aluminum nitrate (Al(NO<sub>3</sub>)<sub>3</sub>). The use of Al/Ag<sub>3</sub>PO<sub>4</sub>, for the first time as a heterogeneous catalyst in organic chemistry, offers a new, efficient, and green pathway for synthesizing 1,2-dihydro-l-phenyl-3H-naphth[1,2-e]-[1,3]oxazin-3-one derivatives by one-pot three-component cyclocondensation of b-naphthol, aryl aldehyde, and urea. The structure and the morphology of the prepared catalyst were characterized by spectroscopic methods such as X-Ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FT-IR), and dispersive X-ray spectrometry coupled with a scanning electron microscope (EDX-SEM). In addition, the optimization of the reaction parameters was carried out considering the effect of catalyst amount, the temperature, and the solvent. The procedure described herein allowed a comfortable preparation of oxazine derivatives with excellent yields, short reaction times, and in the absence of organic solvent.</p>

Synthesis of new pyrido[2,3-d]pyrimidin-5-one, pyrido[2,3-d]pyrimidin-7-one, and pyrimidino[4,5-d][1,3]oxazine derivatives from 5-acetyl-4-aminopyrimidines

Synthesis of new pyrido[2,3-d]pyrimidin-5-one, pyrido[2,3-d]pyrimidin-7-one, and pyrimidino[4,5-d][1,3]oxazine derivatives from 5-acetyl-4-aminopyrimidines

Tricyclic Triazoles as σ1 Receptor Antagonists for Treating Pain.

The synthesis and pharmacological activity of a new series of 5a,7,8,8a-tetrahydro-4H,6H-pyrrolo[3,4-b][1,2,3]triazolo[1,5-d][1,4]oxazine derivatives as potent sigma-1 receptor (σ1R) ligands are reported. A lead optimization program aimed at improving the aqueous solubility of parent racemic nonpolar derivatives led to the identification of several σ1R antagonists with a good absorption, distribution, metabolism, and excretion in vitro profile, no off-target affinities, and characterized by a low basic pKa (around 5) that correlates with high exposure levels in rodents. Two compounds displaying a differential brain-to-plasma ratio distribution profile, 12lR and 12qS, exhibited a good analgesic profile and were selected as preclinical candidates for the treatment of pain.

Nano-Fe3O4/TiCl2/cellulose as an Efficient and Ggreen Magnetic Nanocatalyst for the Synthesis of 2,3-Dihydro-2-substituted-1H-naphtho[1,2-e][1,3]oxazine Derivatives

Nano-Fe3O4/TiCl2/cellulose as a green and recyclable nanocatalyst was synthesized and characterized by FT-IR, FESEM, TEM, XRF, BET, VSM, EDX and XRD. The prepared magnetic nanocatalyst was applied for the synthesis of 2,3-dihydro-2-substituted-1H-naphtho[1,2-e][1,3]oxazine under room temperature grinding condition. Short reaction time, high yield, green media, easy work-up, simple magnetic recovery and reusability of the catalyst are the important features of the present protocol.

Syntheses, Biological and Material Significance of Dihydro[1,3]oxazine Derivatives: An Overview

Dihydro[1,3]oxazines are an important class of heterocyclic compounds having a wide range of biological and material properties. Medicinally, they possess diverse pharmacological activities, such as bactericidal, fungicidal, microbiocidal, antitumor, anti-HIV, and anti-inflammatory agents. Apart from being biologically active, they are materially useful for making polybenzoxazines. Polybenzoxazines are a novel class of non-conjugated thermosetting materials that belong to the family of addition-curable phenolic resins. They have lucrative properties such as small shrinkage in curing, low water absorption, good thermal stability, and there is no release of volatile materials during cure, and no need for catalyst and inexpensive raw materials. Further, the flexibility in designing a monomer gives polybenzoxazines an additional edge over ordinary phenolic resins. This review briefly describes the syntheses, including eco-friendly strategies, and biological and material significance of various dihydro[1,3]oxazine derivatives.

Preparation and Characterization of New Heterocyclic Derivatives, Six and Five Ring from Acetanilide

The aim of the study synthesis of new heterocyclic derivatives (six and five ring) from acetanilide. Firstly the chalcones have been synthesized from the reaction acetanilide with aromatic aldehyde [ 2-nitrobenzaldyhade, 4- dimethylaminobenzaldehyde, 2-naphthaldehyde ] in dilute solution of ethanolic sodium hydroxide at room temperature. This reaction occurs depending on Claisen Schmidt condensation, then a new oxazine and thiazine derivatives (six ring) have been synthesized by the reaction chalcones with urea and thiourea. Finally the synthesized chalcones were reacted with hydrazine hydrate to produce new pyrazol derivatives (five ring). All derivatives were characterized by physical properties, FTIR, 1H-NMR and 13C-NMR spectra.

Gold‐catalyzed Cyclization of Non‐conjugated Ynone‐oxime Derivatives: Incorporation of Solvent Molecule

AbstractAuııı‐promoted cyclization reaction of ynone‐oxime derivatives furnished 4H‐1,2‐oxazine ring under mild reaction conditions. When an alcohol is present in the reaction media, it was attached to the oxazine ring by the second activation of cyclic intermediate with a gold catalyst. Cholesterol, propargyl alcohol, phenol, and some of the different alcohol derivatives with alkyl chain were bonded to the oxazine ring in good yields. While amine derivatives did not attach to the ring under optimized reaction conditions, the molecule with the thiol group deactivated the gold catalyst under the same reaction conditions and did not give any cyclic products. With the obtained cyclization protocol, 11 unknown oxazine derivatives were synthesized and characterized. The proposed cyclization mechanism was drawn according to the two independent control experiments, DFT optimization, and NBO charges.

Withdrawal Notice: Green Chemistry Synthesis Methods of Oxazine and Thiazine Derivatives as Promising Scaffolds in Medicinal Chemistry: A Mini-Review

The article has been withdrawn at the request of the authors and editor of the journal <b>Mini-Reviews in Organic Chemistry</b> due to incoherent content. <p> The Bentham Editorial Policy on Article Withdrawal can be found at <a href=https://benthamscience.com/editorial-policies-main.php>https://benthamscience.com/editorial-policies-main.php</a></p> <p> <b>Bentham Science Disclaimer:</b> <p> It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

One-Pot Green Method for the Synthesis of Oxazine Derivatives Under Aqueous Medium

A simple, convenient, and environmentally friendly method for the synthesis of 1,3-oxazine derivatives has been developed under aqueous conditions. The reaction proceeds via one pot multicomponent condensation of ? or ?- naphthol, aromatic aniline and formaldehyde using polyphosphoric acid as green catalyst. The current protocols are simple, requires less reaction time and provides high yields. Non-polluting synthetic procedures are used to avoid harmful effects of organic solvents on the environment.

An efficient protocol for the synthesis of oxazine derivatives using a carbocatalyst in aqueous medium

Reduced graphene oxide (rGO) is a suitable alternative to toxic metal-based catalysts, due to its large surface area, sp2 carbon backbone and oxygen functionalities that can interact with organic moieties and disperse in water. We have reported herein the synthesis of 1,3-oxazines via multicomponent reaction of various amines, formaldehyde and sesamol/2-hydroxy-1,4-naphthaquinone/6-hydroxyquinoline in aqueous medium for the first time using rGO as the catalyst at 80 °C. The reactions were complete in 5–15 min and afforded the products in excellent yields. Short reaction time, easy separation of recyclable catalyst and green methodology are advantages of this protocol.

Accessing Dihydro-1,2-oxazine via Cloke-Wilson-Type Annulation of Cyclopropyl Carbonyls: Application toward the Diastereoselective Synthesis of Pyrrolo[1,2-b][1,2]oxazine.

A convenient additive-free synthesis of dihydro-4H-1,2-oxazines via a Cloke-Wilson-type ring expansion of the aryl-substituted cyclopropane carbaldehydes with the hydroxylamine salt is introduced. Comparatively less active cyclopropyl ketones also follow a similar protocol if supplemented by catalytic p-toluene sulfonic acid monohydrate. The transformation is performed in an open-to-air flask as it shows negligible sensitivity toward air/moisture. Dihydro-4H-1,2-oxazines when subjected to cycloaddition with the cyclopropane diester afford a trouble-free formulation of the valued hexahydro-2H-pyrrolo[1,2-b][1,2]oxazine derivatives. A cascade one-pot variant of this two-step strategy offers a comparable overall yield of the final product.

L-proline catalyzed unprecedented synthesis of novel naphtho-bis[1,3]oxazines under solvent-free conditions

An unprecedented l-proline-mediated one-pot sequential synthesis of novel 3,10-diphenyl-2,3,4,9,10,11-hexahydronaphtho[1,2-e:4,3-e′]bis[1,3]oxazine derivatives from 2,3-dihydroxynaphthalene, formaldehyde, and anilines under solvent-free conditions has been reported. Under the optimized reaction conditions, a broad range of substituted anilines and 2,3-dihydroxynaphthalene were found to participate in this transformation, thus affording new 3,10-diphenyl-2,3,4,9,10,11-hexahydronaphtho[1,2-e:4,3-e′]bis[1,3]oxaz-ines in good to excellent yields. This green procedure offers several advantages such as high atom economy, mild reaction conditions, short reaction time, easy workup and column chromatography-free method with a wide range of functional group tolerance.

Overview of Recent Advances in 3-Hydroxycoumarin Chemistry as a Bioactive Heterocyclic Compound

Coumarins or benzo-2-pyrone derivatives are one of the most significant families of natural compounds and are also important in synthetic organic chemistry. They have been widely used as starting materials or precursor molecules in the pharmaceutical, perfumery and agrochemical industries, etc. Hydroxycoumarins are an important class of coumarin compounds that possess several physical, chemical and biological properties. Among the hydroxycoumarins, 3-hydroxycoumarin seems to be the most important because of its numerous chemical, photochemical and biological properties. However, this compound remains less well known compared to others of the same class such as 7-hydroxycoumarin and 4-hydroxycoumarin. This study is therefore devoted to 3-hydroxycoumarin and its applications. The main purpose of this review is to summarize and document the recent advances on 3-hydroxycoumarin, concerning the main routes of its synthesis, its reactivity, its applications in different fields of biology. Several methods for the synthesis of 3-hydroxycoumarin have been described in the literature, most of which use salicylic aldehyde and 1-(2-hydroxyphenyl)ethanone as starting compounds. Other synthesis pathways exist, but they are based on intermediate synthesis compounds. Concerning the reactivity of 3-hydroxycoumarin, many heterocyclic compounds obtained from 3-hydroxycoumarin have been reported in the literature. Among these heterocycles are pyrido[2,3-c]coumarin derivatives, chromeno[4,3-e][1,3]oxazine derivatives, dihydropyrano[2,3-c] chromenes and 3-coumarinyl carboxylates. Various researches have also concerned the biological properties of this compound. It appears from these numerous studies that 3-hdroxycoumarin is used in fields such as genetics, pharmacology, microbiology, etc.

Synthesis, anti-inflammatory evaluation and in silico studies of naphtho[1,2-e][1,3]oxazine derivatives as potential non-steroidal anti-inflammatory agents

A small molecule library of trans-1,3-diaryl-1H-naphtho[1,2-e][1,3]oxazines 4 is synthesised through multicomponent reactions involving aliphatic amines, aromatic aldehydes and β-naphthol using a heterogeneous catalyst, SiO2.HClO4, and ethanol as the solvent. The anti-inflammatory activities of the synthesised compounds are evaluated together with in silico studies. 1,3-Bis(4-chlorophenyl)-2-ethyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine (4h) shows the best activity with IC50 = 4.807 µg/mL in the heat-induced haemolysis, while 1,3-Bis(5-bromothiophen-2-yl)-2-ethyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine (4c) shows significantly high anti-inflammatory activity (IC50 = 5.5 µg/mL) in comparison with standard drugs, such as sodium diclofenac. In addition, molecular docking simulation study confirms the in-depth molecular interaction of the two lead compounds, 4c and 4h with better binding affinities and docking scores at the active site of the COX-2 enzyme compared with diclofenac.

Ring Expansion and 1,2-Migration Cascade of Benzisoxazoles with Ynamides: Experimental and Theoretical Studies.

Demonstrated herein is an AuI -catalyzed annulation of sulfonyl-protected ynamides with substituted 1,2-benzisoxazoles for the synthesis of E-benzo[e][1,3]oxazine derivatives. The transformation involves the addition of benzisoxazole to the gold-activated ynamide, ring expansion of the benzisoxazole fragment to provide an α-imino vinylic gold intermediate, and 1,2-migration of the sulfonamide motif to the masked carbene center to deliver the respective ring-expanded benzo[e][1,3]oxazine of predominant E configuration. A trapping experiment justifies the participation of the α-imino masked gold carbene. DFT computations also support the hypothesized mechanism and rationalize the product stereoselectivity.