D. Srinivasulu

Microwave Assisted Synthesis of Biologically Active α-Aminophosphonates Catalyzed by Nano-BF3·SiO2 under Solvent-Free Conditions

Abstract An efficient and high-yield synthesis of a class of new α-aminophosphonate derivatives as diethyl α-aryl/2-thienyl-α-[2-(phenylthio)phenylamino]methylphosphonates 6a–j in short reaction times from three component coupling reactions (Kabachnik-Fields reaction) of 2-aminodiphenylsulfide 3, substituted phenyl/heterocyclic aldehydes 4a–j, and diethyl phosphite 5 is reported. The reaction proceeds smoothly in the presence of the catalyst, nano-silica-supported boron trifluoride (BF3·SiO2) without using solvent under microwave irradiation. The title compounds were tested for in vitro antibacterial and antifungal activities at concentrations of 100 and 200 μg/disc. Minimum inhibitory concentrations (MICs) were also examined. Supplementary materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures and tables. GRAPHICAL ABSTRACT

EcoFriendly Synthesis of Tetrahydropyrimidine Derivatives in Aqueous Medium Under Ultrasonic Irradiation

Abstract A simple, efficient, and ecofriendly procedure was developed for the synthesis of 2-substituted 1,4,5,6-tetrahydropyrimidine derivatives catalyzed by N-bromosuccinimide using ultrasonic irradiation in aqueous medium. Prominent advantages of this new method are good yields, aqueous medium, short reaction times, and easy workup procedure. The compounds were characterized by infrared, NMR, liquid chromatography–mass spectrometry, and elemental analyses. GRAPHICAL ABSTRACT

Tween-20: An Efficient Catalyst for One-Pot Synthesis of α-Aminophosphonates in Aqueous Media

Abstract A green one-pot three-component synthesis has been developed for α-aminophosphonates by condensation of aldehydes, amines, and diethylphosphite by using nonionic surfactant Tween-20 as catalyst in aqueous media. The results showed that this synthetic route for α-aminophosphonates takes just 25–60 min for completion at 60 °C and affords 64%–91% yields depending on the nature of the amine substrates. The major advantages of this novel method are green reaction conditions with water as solvent, simple workup, less reaction times, and high to moderate yields. GRAPHICAL ABSTRACT

CeCl3·7H2O Catalyzed, Microwave-Assisted High-Yield Synthesis of α-Aminophosphonates and their Biological Studies

Abstract A new class of diethyl(3,5-dibromo-4-hydroxyphenylamino) (substituted phenyl/heterocyclic) methylphosphonates 4(a–j) has been synthesized by one-pot three component simultaneous reaction (Kabachnik–Fields) of 4-amino-2,6-dibromophenol 1, substituted heterocyclic/phenyl aldehydes 2(a–j), and diethylphosphite 3 using a Lewis acid catalyst, CeCl3·7H2O (5 mol%) under microwave irradiation as well as conventional conditions. It was observed that microwave irradiation method is more facile, efficient, and advantageous with respect to reaction time and yields. The structures of all the synthesized compounds were supported by analyzing IR, 1H/13C/31P NMR, and mass spectral data. The synthesized compounds were screened for their in vitro antimicrobial and antioxidant activities. GRAPHICAL ABSTRACT

Synthesis and antimicrobialactivity of 2‐alkylcarbamato‐2,3‐dihydro‐5‐propylthio‐1H‐1,3,2‐benzodiazaphosphole 2‐oxides

Novel 2-alkylcarbamato/thiocarbama-to-2,3-dihydro-5-propylthio-1H-1,3,2-benzodiazaphos-phole 2-oxides (4a–J) were synthesized by cyclization of 4-propylthio-1,2-phenylenediamine (3) with the corresponding dichlorophosphoryl carbamates/thiocarbamates (2a–J) that were obtained by the addition of alcohols/thiols to isocyanatophosphoryl dichloride (1). The structures of the title compounds were confirmed by the 1H, 13C, 31P NMR, and mass spectral studies. Some of these products were found to possess significant antimicrobial activity.

Synthesis, Characterization, and Antibacterial Activity of New Linezolid-Based Phosphoramidate Derivatives

GRAPHICAL ABSTRACT Abstract A series of new linezolid-based phosphoramidate derivatives 5(a-j) were synthesized in high yields from a linezolid intermediate, [3-(3-fluoro-4-morpholinophenyl)-5-(hydroxymethyl) oxazolidin-2-one] to develop new antibacterial agents. The structures of the newly synthesized compounds were elucidated by mass, 1H, 13C & 31P NMR, IR and Elemental analysis spectral characterization data. All the synthesized compounds were screened for their antibacterial activity against recipient (Streptomycin resistant), donor (Rifampin resistant), and mutant (Streptomycin resistant) Gram –Ve E. coli strains using Amoxiclav as a standard.

Nano-BF3.SiO2 Catalyst-Promoted Michaelis-Arbuzov Reaction: Solvent-Free Synthesis and Antimicrobial Evaluation

GRAPHICAL ABSTRACT Abstract A simple, convenient synthetic route for the synthesis of novel dialkyl heteroaryl phosphonates by a reusable and green nano-BF3.SiO2 solid catalyst under solvent-free conditions through Michaelis–Arbuzov reaction with high yields is presented. All the newly synthesized compounds were characterized by spectral data and screened for their antimicrobial activity. Some of the compounds exhibited potent antibacterial activity against all the tested pathogens, and warrant further investigation.

Synthesis of novel N-aryl-4-[6-(2-fluoropyridin-3-yl)quinazolin-2-yl]-piperazine-1-carboxamide or -carbothioamide derivatives and their antimicrobial activity

A series of novel N-aryl-4-[6-(2-fluoropyridin-3-yl)quinazolin-2-yl]-piperazine-1-carboxamide or -carbothioamide derivatives was synthesized by cyclization of 5-bromo-2-fluorobenzaldehyde and guanidine carbonate in the presence of dimethylacetamide followed by treatment with isoamylnitrite and diiodomethane in the presence of copper iodide to afford 6-bromo-2-iodoquinazoline. The latter was treated with piperazine in the presence of triethylamine followed by (2-fluoropyridin-3-yl)boronic acid in the presence of Pd(PPh3)2Cl2 to afford 6-(2-fluoropyridin-3-yl)-2-(piperazin-1-yl)quinazoline which was further treated with various substituted arylisocyanates and arylisothiocyanates to obtain the title compounds. The chemical structures of the synthesized compounds were confirmed by means of LC-MS, 1H, 13C NMR, IR, and mass spectra and elemental analysis. All the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-positive and two Gram-negative bacterial species, as well as two different strains of antibiotic-resistant E. coli and for antifungal activity against two fungal strains. Some of the compounds have shown potential antimicrobial activity.

Syntheses and Antimicrobial Activity of 2-Substituted-2,3-Dihydro-3-(4′-Bromophenyl)-1H-Naphth[1,2-e][1,3,2]Oxazaphosphorin 2-Oxides/Sulfides

Abstract The syntheses of the first examples of 2-aryloxy-2,3-dihydro-3-(4′-bromophenyl)-1H-naphth [1,2-e][1,3,2]-oxazahosphorin 2-oxides (3a-g) have been achieved from the reaction of equimolar quantities of l-(4-bromoonilinomethyl)-2-naphthol (1) with various arylphosphomdichloridates in dry toluene in the presence of triethylamine at 50–55 °C. 2-Benzyloxyl/aryloxy/arylthio/bis(2-chloroethyl)amino-2,3-dihydro-3-(4′-bromophenyl)- 1 H-naphth[1,2-e][1,3,2]-oxazaphosphorin 2-sulphides(3h-o)have been synthesized through an intermediate monochloride, namely 2chloro-2,3-dihydro-3-(4′-bromophenyl)-1H-naphth[1,3,2] oxazaphosphorin 2-sulfide (2). The structures of all products were confirmed by IR, 1H, C and 31 P NMR data as well as via mass, spectral analysis. All compounds were screened for antibacterial activity against Bacillus subtilis and Klebsiella pneumoniae and for antifungal activity against Aspergillus niger and Curvularia lunata. A majority of the products exhibited significant activity in the assays.

Inhibition of LPS-induced no production in RAW264.7 cell lines: synthesis and molecular modeling of α-ketophosphonates of febuxostat

GRAPHICAL ABSTRACT ABSTRACT In an effort to develop novel anti-inflammatory agents, we synthesized phosphorylated derivatives of febuxostat using various phosphates/phosphonites by Michaelis-Arbuzov reaction. Their inhibitory activity on nitric oxide (NO) production, reactive oxygen species (ROS) production and cytotoxicity were evaluated using lipopolysaccharide (LPS) activated macrophages RAW264.7 assay, flow-cytometry analysis and MTT method respectively. Some of these compounds showed potent inhibition of NO and ROS production without obvious cytotoxicity. Furthermore, docking simulations were performed to positional compounds 3g, 3h, 3i and 3j into the COX-2 active site to determine the probable binding model. Physicochemical parameters revealed that most of the compounds possessed drug-like properties.