First synthesis of α-aminophosphonates from natural porphyrin derivatives by the Kabachnik—Fields reaction

A preparative procedure is proposed for the synthesis of α-aminophosphonates of natural porphyrins by the microwave-assisted Kabachnik—Fields reaction.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 256–259, January, 2005.     

Diastereoselective Synthesis of Enantiopure α-Aminophosphonic Acid Derivatives: Pudovik Reaction in Stereoselective Synthesis (Dedicated to A. N. Pudovik, 1916–2006)

In this report, we present the application of Pudovik reaction in the synthesis of chiral organophosphorus compounds and shown this reaction to be a promising way to enantiopure aminophosphonic acid derivatives. Cyclization reactions are a new, most efficient strategy for stereoselective synthesis of α-aminophosphonates, namely an intramolecular type of interaction of the P(III) atom and an imino group.     

Synthesis and Application of N-Tosyl Piperidinyl-Containing α-Aminophosphonates

Abstract

A series of novel (4′-tosyl) piperidin-4-yl containing α-aminophosphonates were synthesized by a one-pot reaction, efficiently catalyzed by magnesium perchlorate, under solvent-free conditions from 1-tosylpiperidin-4-one, substituted aromatic amines, and diethyl phosphite (DEP). The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, ³¹P NMR, and HRMS spectroscopy. A single-crystal X-ray structure of diethyl 4-(2-chlorophenyl) amino-1-(4’-methylbezenesulfonyl) piperidin-4-yl-phosphonate (2a) was obtained, and some of the title compounds displayed insecticidal activities against Plutella xylostella.

Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional figures and tables.     

Synthesis,Characterization, and Biological Screening of Some Novel Thiazolidin-4-One and α-Aminophosphonate Derivatives

Abstract

Synthesis of some new functionalized thiazolidin-4-ones and α-amino phosphonate derivatives has been reported. The imines were synthesized from the reaction of various substituted anilines with 1-phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde in ethanol at reflux condition. The corresponding thiazolidin-4-ones and α-aminophosphonates were prepared by reaction of imines with mercaptoacetic acid and triethyl phosphite, respectively. The structures of the newly synthesized compounds were confirmed by IR, ¹H NMR, and mass spectral data and were evaluated for their antimicrobial activities.

GRAPHICAL ABSTRACT      

Efficient and green syntheses of novel γ-aminophosphonate and phosphine oxide derivatives

Two synthetic protocols leading to novel γ-aminophosphonate and phosphine oxide derivatives, by reductive amination of γ-phosphonylketones, are reported. The first method involved a two-step procedure. Imine intermediates were first isolated from the p-toluenesulfonic acid-catalyzed reaction of primary amines with γ-ketophosphonates and phosphine oxides, then reduced with NaBH₄ in refluxing ethanol. The second method consists of a one-pot procedure which includes the condensation of γ-ketophosphonates and phosphine oxides with primary amines, in the presence of molecular sieves, followed by reduction with NaBH₄. These methods offer significant advantages over prior reports, such as efficiency, generality, and good yields. Furthermore, they are green protocols avoiding hazardous hydrides and solvents.     

Electron ionization mass spectra of organophosphorus compounds Part V: Mass fragmentation modes of some azolyl,azinyl, and azepinyl phosphonates as cyclic α-aminophosphonates

Mass fragmentation pathways of eight synthetic organophosphorus compounds, belonging to azolyl, azinyl, and azepinyl phosphonates as cyclic α-aminophosphonates 1a,b–4a,b were investigated by electron impact mass spectrometry with the aim of obtaining a better understanding of their fragmentation processes. The intensity of the recorded molecular ion peaks showed moderate values. Compounds 1a,b–3a,b have almost identical fragmentation routes via easy elimination of phosphonate groups which can be fragmented into the cation PO₂ as base peaks. On the contrary, compounds 4a,b started their fragmentation via removal of 4-chlorophenyl moieties.     

Synthesis,characterization, and application of [1-methylpyrrolidin-2-one-SO3H]Cl as an efficient catalyst for the preparation of α-aminophosphonate and docking simulation of ligand bond complexes of cyclin-dependent kinase 2

A sulfonic acid functionalized ionic liquid was designed, synthesized and successfully used as a Brønsted acid catalyst for the one-pot synthesis of α-aminophosphonates containing benzothiazole at room temperature under solvent-free conditions in excellent yields. The advantages of this method are the reusability of the catalyst, high conversion, short reaction time, and simple experimental procedure. A computer modeling and docking simulation of ligand bond complexes of cyclin-dependent kinase 2 are presented. The results indicate that diethyl ((4-(dimethylamino) phenyl) ((6-nitrobenzo[d]thiazol-2-yl) amino)methyl)phosphonate was found to be the best selective inhibitor of cyclin-dependent kinase 2.     

Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis,Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species

The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik–Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76–700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.     

Cross-dehydrogenative coupling strategy for phosphonation and cyanation of secondary N-alkyl anilines by employing 2,3-dichloro-5,6-dicyanobenzoquinone

The cross-dehydrogenative coupling strategy for metal-free phosphonation and cyanation of secondary N-alkyl anilines has been developed firstly under mild reaction conditions. Based on detailed optimization of reaction conditions, the substrate generality of N-alkyl anilines and various hydrogen phosphonates has been investigated, and a series of versatile α-aminophosphonates and α-aminonitriles were therefore furnished in good to excellent yields. A plausible collective reaction mechanism through dehydrogenation to imine formation, then to respective α-aminophosphonates and α-aminonitriles was proposed.