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A representative set of the simplest dialkyl polyfluoroalkylphosphonates was in silico profiled against their absorption, distribution, metabolism, and excretion with the use of the SwissADME tool. Promising results of the screening led us to attempt to synthesize the title compounds for further biological investigations. Detailed experimental and quantum-theoretical (DFT) investigations were performed to reveal that the studied compounds could not be obtained through the standard Michaelis–Arbuzov or Michaelis–Becker reactions. Kinetic studies showed that trimethyl phosphite undergoes a reaction with 1,1,1-trifluoro-2-iodoethane several orders of magnitude slower than a side reaction. The difficulty was overcome by developing a simple three-step synthesis path that involves only readily available substrates. The newly synthesized substances were tested against several cell lines. The in vitro research revealed that both dimethyl and diethyl (2,2,3,3,3-pentafluoropropyl)phosphonate exhibited toxicity towards glioblastoma cells (U-87 MG) at a considerably lower concentration than known chemotherapeutics.

The microreview covers three, most powerful, strategies of the synthesis of phosphinine (systematically called phosphabenzene) starting from pyrylium salts, five-membered heterocycles, and reagents with C≡P bond.

Pyrroles, an important class of heterocyclic compounds found in naturally occurring products, represent an interesting biologically active scaffold for drug design. Recently we have synthetized a series of five new fluorinated pyrrole derivatives for potential anticancer applications. All new compounds contain a trifluoromethyl and N-benzyl group, but they are different from each other by bearing a phenyl, ethoxycarbonyl or carboxylic moiety, with two of them possessing an additional phosphonyl function. The aim of this study was to evaluate anticancer activity of the new compounds in human lung and breast cancer cells. We found that compound 3, bearing a phosphonyl and phenyl group, was the most effective in attenuating growth of A549 and MCF-7 cells in a dose dependent manner with IC50 36.5 μM ± 1.80 and 27.9 μM ± 1.68, respectively. Compound 3 inhibited cancer cell proliferation by cell cycle arrest at G1 phase as detected by flow cytometry analysis. Furthermore, compound 3 induced apoptosis of A549 cells by activation of caspase-3. Cancer cell migration rate was significantly inhibited when A549 and MCF-7 cells were cultured in the presence of the compound. These results demonstrate that a novel trifluoromethyl-functionalized phosphonopyrrole with a phenyl group might be a promising pyrrole analogue with anticancer potential.

The hitherto unknown addition of the lithium salt of dimethyl methylphosphonate 6 to the N-substituted phthalimides 7 is described. This reaction allows the synthesis of new systems in which the phosphono group is connected to the heterocyclic skeleton of an isoindolinone at the 3-position by one methylene group.

In the title compound, C22H23F3NO3P, the dihedral angles between the pyrrole ring and the benzyl and phenyl rings are 81.38 (7) and 46.21 (8)°, respectively. The ethyl phosphate groups present with P—O—C—C torsion angles of −178.47 (10) and 106.72 (16)°, and an intramolecular C—H...O hydrogen bond occurs. In the extended structure, molecules are linked by C—H...O and C—H...F hydrogen bonds to generate [001] chains.

New trifluoromethyl-functionalized 2-phosphonopyrroles were obtained by 5-exotrig cyclization of trifluoromethyl and phosphonyl functionalized enaminoketones. GRAPHICAL ABSTRACT

The synthesis of diethyl [2-(2-alkyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)ethyl]phosphonates and diethyl [3-(2-alkyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)propyl]phosphonates, via metallation (sec-BuLi) of N-substituted isoindolin-1-ones and then the reaction of the generated lithiated species 4 with diethyl vinylphosphonate or diethyl 3-bromopropylphosphonate, respectively, is described.

Syntheses of a series of compounds bearing a 1-(fluorophenyl)piperazin-4-ylmethyl moiety, namely dialkyl 1-(fluorophenyl)piperazin-4-ylmethyl phosphonates 3a–f, diethyl 2-[1-(fluorophenyl)piperazin-4-yl]-ethyl phosphonates 4a,b, diethyl 3-[1-(4-fluorophenyl)-piperazin-4-yl]-propyl phosphonate 5, and di[1-(fluorophenyl)piperazin-4-yl]methanes 6a,b were performed, and some of them were screened for their affinity for serotonin 5-HT1A, 5-HT6, and 5-HT7 receptors. Moderate interactions with these receptors were demonstrated.