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Bioorganic & Medicinal Chemistry Dec 2023Clinically manifested resistance of bacteria to antibiotics has emerged as a global threat to society and there is an urgent need for the development of novel classes of... (Review)
Review
Clinically manifested resistance of bacteria to antibiotics has emerged as a global threat to society and there is an urgent need for the development of novel classes of antibacterial agents. Recently, the use of phosphorus in antibacterial agents has been explored in quite an unprecedent manner. In this comprehensive review, we summarize the use of phosphorus-containing moieties (phosphonates, phosphonamidates, phosphonopeptides, phosphates, phosphoramidates, phosphinates, phosphine oxides, and phosphoniums) in compounds with antibacterial effect, including their use as β-lactamase inhibitors and antibacterial disinfectants. We show that phosphorus-containing moieties can serve as novel pharmacophores, bioisosteres, and prodrugs to modify pharmacodynamic and pharmacokinetic properties. We further discuss the mechanisms of action, biological activities, clinical use and highlight possible future prospects.
Topics: Phosphorus; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Bacteria; Organophosphonates
PubMed: 37939493
DOI: 10.1016/j.bmc.2023.117512 -
Nature Communications Jul 2023Despite the growing importance of fluorinated organic compounds in pharmaceuticals, agrochemicals, and materials science, the introduction of fluorine into organic...
Despite the growing importance of fluorinated organic compounds in pharmaceuticals, agrochemicals, and materials science, the introduction of fluorine into organic molecules is still a challenge, and no catalytic fluorocarbonylation of aryl/alkyl boron compounds has been reported to date. Herein, we present the development of palladium and phosphine synergistic redox catalysis of fluorocarbonylation of potassium aryl/alkyl trifluoroborate. Trifluoromethyl arylsulfonate (TFMS), which was used as a trifluoromethoxylation reagent, an easily handled and bench-scale reagent, has been employed as an efficient source of COF. The reaction operates under mild conditions with good to excellent yields and tolerates diverse complex scaffolds, which allows efficient late-stage fluorocarbonylation of marked small-molecule drugs. Mechanistically, the key intermediates of labile Brettphos-Pd(II)-OCF complex and difluoro-Brettphos were synthesized and spectroscopically characterized, including X-ray crystallography. A detailed reaction mechanism involving the synergistic redox catalytic cycles Pd(II)/(0) and P(III)/(V) was proposed, and multifunction of phosphine ligand was identified based on F NMR, isotope tracing, synthetic, and computational studies.
PubMed: 37524725
DOI: 10.1038/s41467-023-40180-6 -
Beilstein Journal of Organic Chemistry 2023Photoredox catalysis plays a crucial role in contemporary synthetic organic chemistry. Since the groundbreaking work of Shang and Fu on photocatalytic decarboxylative... (Review)
Review
Photoredox catalysis plays a crucial role in contemporary synthetic organic chemistry. Since the groundbreaking work of Shang and Fu on photocatalytic decarboxylative alkylations in 2019, a wide range of organic transformations, such as alkylation, alkenylation, cyclization, amination, iodination, and monofluoromethylation, have been progressively achieved using a combination of iodide and PPh. In this review, we primarily focus on summarizing the recent advancements in inexpensive and readily available iodide/phosphine-mediated photoredox radical transformations.
PubMed: 38033449
DOI: 10.3762/bjoc.19.131 -
Inorganic Chemistry Oct 2023A series of -substituted acenaphthene-based phosphine selenoether bidentate ligands Acenap(PrP)(SeAr) (-, Acenap = acenaphthene-5,6-diyl, Ar = Ph, mesityl,...
A series of -substituted acenaphthene-based phosphine selenoether bidentate ligands Acenap(PrP)(SeAr) (-, Acenap = acenaphthene-5,6-diyl, Ar = Ph, mesityl, 2,4,6-trisopropylphenyl and supermesityl) were prepared. The rigid acenaphthene framework induces a forced overlap of the phosphine and selenoether lone pairs, resulting in a large magnitude of through-space coupling, ranging from 452 to 545 Hz. These rigid ligands - were used to prepare a series of selected late d-block metals, mercury, and borane complexes, which were characterized, including by multinuclear NMR and single-crystal X-ray diffraction. The Lewis acidic motifs (BH, Mo(CO), Ag, PdCl, PtCl, and HgCl) bridge the two donor atoms (P and Se) in all but one case in the solid-state structures. Where the bridging motif contained NMR-active nuclei (B, Ag, Ag, Pt, and Hg), and couplings are observed directly, in addition to the altered in the respective NMR spectra. The solution NMR data are correlated with single-crystal diffraction data, and in the case of mercury(II) complexes, they are also correlated with the solid-state NMR data and coupling deformation density calculations. The latter indicate that the through-space interaction dominates in free , while in the complex, the main coupling pathway is via the metal atom and not through the carbon framework of the acenaphthene ring system.
PubMed: 37722079
DOI: 10.1021/acs.inorgchem.3c02255 -
Frontiers in Chemistry 2024Asymmetric catalysis stands at the forefront of modern chemistry, serving as a cornerstone for the efficient creation of enantiopure chiral molecules characterized by... (Review)
Review
Asymmetric catalysis stands at the forefront of modern chemistry, serving as a cornerstone for the efficient creation of enantiopure chiral molecules characterized by their high selectivity. In this review, we delve into the realm of asymmetric catalytic reactions, which spans various methodologies, each contributing to the broader landscape of the enantioselective synthesis of chiral molecules. Transition metals play a central role as catalysts for a wide range of transformations with chiral ligands such as phosphines, -heterocyclic carbenes (NHCs), etc., facilitating the formation of chiral C-C and C-X bonds, enabling precise control over stereochemistry. Enantioselective photocatalytic reactions leverage the power of light as a driving force for the synthesis of chiral molecules. Asymmetric electrocatalysis has emerged as a sustainable approach, being both atom-efficient and environmentally friendly, while offering a versatile toolkit for enantioselective reductions and oxidations. Biocatalysis relies on nature's most efficient catalysts, i.e., enzymes, to provide exquisite selectivity, as well as a high tolerance for diverse functional groups under mild conditions. Thus, enzymatic optical resolution, kinetic resolution and dynamic kinetic resolution have revolutionized the production of enantiopure compounds. Enantioselective organocatalysis uses metal-free organocatalysts, consisting of modular chiral phosphorus, sulfur and nitrogen components, facilitating remarkably efficient and diverse enantioselective transformations. Additionally, unlocking traditionally unreactive C-H bonds through selective functionalization has expanded the arsenal of catalytic asymmetric synthesis, enabling the efficient and atom-economical construction of enantiopure chiral molecules. Incorporating flow chemistry into asymmetric catalysis has been transformative, as continuous flow systems provide precise control over reaction conditions, enhancing the efficiency and facilitating optimization. Researchers are increasingly adopting hybrid approaches that combine multiple strategies synergistically to tackle complex synthetic challenges. This convergence holds great promise, propelling the field of asymmetric catalysis forward and facilitating the efficient construction of complex molecules in enantiopure form. As these methodologies evolve and complement one another, they push the boundaries of what can be accomplished in catalytic asymmetric synthesis, leading to the discovery of novel, highly selective transformations which may lead to groundbreaking applications across various industries.
PubMed: 38783896
DOI: 10.3389/fchem.2024.1398397 -
Nature Jul 2023The chemical activation of water would allow this earth-abundant resource to be transferred into value-added compounds, and is a topic of keen interest in energy...
The chemical activation of water would allow this earth-abundant resource to be transferred into value-added compounds, and is a topic of keen interest in energy research. Here, we demonstrate water activation with a photocatalytic phosphine-mediated radical process under mild conditions. This reaction generates a metal-free PR-HO radical cation intermediate, in which both hydrogen atoms are used in the subsequent chemical transformation through sequential heterolytic (H) and homolytic (H) cleavage of the two O-H bonds. The PR-OH radical intermediate provides an ideal platform that mimics the reactivity of a 'free' hydrogen atom, and which can be directly transferred to closed-shell π systems, such as activated alkenes, unactivated alkenes, naphthalenes and quinoline derivatives. The resulting H adduct C radicals are eventually reduced by a thiol co-catalyst, leading to overall transfer hydrogenation of the π system, with the two H atoms of water ending up in the product. The thermodynamic driving force is the strong P=O bond formed in the phosphine oxide by-product. Experimental mechanistic studies and density functional theory calculations support the hydrogen atom transfer of the PR-OH intermediate as a key step in the radical hydrogenation process.
PubMed: 37380779
DOI: 10.1038/s41586-023-06141-1 -
Molecules (Basel, Switzerland) Jul 2023Here, we report the synthesis of disulfide-reducing agents 2-(dibenzylamino) propane-1,3-dithiol (DPDT) and 2-(dibenzylamino)-2-methylpropane-1,3-dithiol (DMPDT) from...
Here, we report the synthesis of disulfide-reducing agents 2-(dibenzylamino) propane-1,3-dithiol (DPDT) and 2-(dibenzylamino)-2-methylpropane-1,3-dithiol (DMPDT) from serinol and methyl serinol, respectively. DPDT was found to show greater stability than DMPDT. Hence, the effectiveness of DPDT as a reducing agent was evaluated in both liquid and solid phases. The reducing capacity of this agent was comparable to that of DTT.
PubMed: 37513361
DOI: 10.3390/molecules28145489 -
Inorganic Chemistry Oct 2023The reactions of [{(NacNac)Mg}] (nacnac = HC(iPrCNDip)) with PhP═O at 100 °C afforded the phosphinate complex [(NacNac)Mg(OPPh)(OPPh)] . Reactions of with PhP═E...
The reactions of [{(NacNac)Mg}] (nacnac = HC(iPrCNDip)) with PhP═O at 100 °C afforded the phosphinate complex [(NacNac)Mg(OPPh)(OPPh)] . Reactions of with PhP═E (E = S, Se) proceeded rapidly at room temperature to low-coordinate chalcogenide complexes [{(NacNac)Mg}(μ-S)] and [{(NacNac)Mg}(μ-Se)] , respectively. Similarly, reactions of NHC═S ((MeCNR)C═S with R = Me, Et, or Pr) with afforded NHC adducts of magnesium sulfide complexes, [{(NacNac)Mg(NHC)}(μ-S){Mg(NacNac)}] , that could alternatively be obtained by adding the appropriate NHC to sulfide complex . Complex reacted with 1-adamantylazide (AdN) to give [{(NacNac)Mg}(μ-SNAd)] and can form various simple donor adducts in solution, of which [(NacNac)Mg(OAd)}(μ-S)] (OAd = 2-adamantanone) was structurally characterized. The nature of the ionic Mg-E-Mg unit is described by solution and solid-state studies of the complexes and by DFT computational investigations.
PubMed: 37747417
DOI: 10.1021/acs.inorgchem.3c02132 -
Molecules (Basel, Switzerland) Oct 2023A series of phosphorus and selenium -substituted acenaphthene species with the phosphino group oxidized by O, S, and Se has been isolated and fully characterized,...
A series of phosphorus and selenium -substituted acenaphthene species with the phosphino group oxidized by O, S, and Se has been isolated and fully characterized, including by single-crystal X-ray diffraction. The P(V) and Se(II) systems showed fluxional behavior in solution due to the presence of two major rotamers, as evidenced with solution NMR spectroscopy. Using Variable-Temperature NMR (VT NMR) and supported by DFT (Density Functional Theory) calculations and solid-state NMR, the major rotamers in the solid and in solution were identified. All compounds showed a loss of the through-space coupling observed in the unoxidized P(III) and Se(II) systems due to the sequestration of the lone pair of the phosphine, which has been previously identified as the major contributor to the coupling pathway.
PubMed: 37959719
DOI: 10.3390/molecules28217297 -
Chemical & Pharmaceutical Bulletin Sep 2023As an extension of our research on providing a chemical library of side-chain fluorinated vitamin D analogues, we newly designed and synthesized...
As an extension of our research on providing a chemical library of side-chain fluorinated vitamin D analogues, we newly designed and synthesized 26,27-difluoro-25-hydroxyvitamin D (1) and 26,26,27,27-tetrafluoro-25-hydroxyvitamin D (2) using a convergent method applying the Wittig-Horner coupling reaction between CD-ring ketones (13, 14) and A-ring phosphine oxide (5). The basic biological activities of analogues, 1, 2, and 26,26,26,27,27,27-hexafluoro-25-hydroxyvitamin D [HF-25(OH)D] were examined. Although the tetrafluorinated new compound 2 exhibited higher binding affinity for vitamin D receptor (VDR) and resistance to CYP24A1-dependent metabolism compared with the difluorinated 1 and its non-fluorinated counterpart 25-hydroxyvitamin D [25(OH)D], HF-25(OH)D showed the highest activity among these compounds. Osteocalcin promoter transactivation activity of these fluorinated analogues was tested, and it decreased in the order of HF-25(OH)D, 2, 1, and 25(OH)D in which HF-25(OH)D showed 19-times greater activity than the natural 25(OH)D.
Topics: Calcifediol; Calcitriol; Fluorine; Half-Life; Receptors, Calcitriol; Vitamin D3 24-Hydroxylase
PubMed: 37423740
DOI: 10.1248/cpb.c23-00395