Phosphine Derivatives Research Articles

Bonding properties and bond activation of ylides: recent findings and outlook

The interaction of phosphorus and nitrogen ylides with metallic precursors has been examined from different points of view. The first one is related to the bonding properties of the ylides. Ylides with a unique stabilizing group bond through different atoms (the Calpha or the heteroatoms); while ylides with two stabilizing groups never coordinate through the Calpha atom. In the second section we examine the cause of the stereoselective coordination of bisylides of phosphorus, nitrogen and arsenic, and of mixed bisylides. We describe here the very interesting conformational preferences found in these systems, which have been determined and characterized. The DFT study of these bisylides has allowed for the characterization of strong intramolecular PO and AsO interactions, as well as moderate CHO[double bond, length as m-dash]C hydrogen bonds as the source of these conformational preferences. The third topic is related to the amazing reactivity of phosphorus ylides in bond activation processes. Depending on the nature of the metallic precursors, ylides can behave as sources of carbenes, of phosphine derivatives, of other ylides or of orthometallated complexes through P[double bond, length as m-dash]C, P-C or C-H bond activation reactions.

The Chemistry of Phosphinic and Phosphinous Acid Derivatives Containing the t‐Butyl Group as a Single Bulky Substituent: Synthetic, Mechanistic and Stereochemical Aspects

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Electrochemical phosphorylation of unsaturated hydrocarbons

It is shown that phosphine derivatives, first of all, primary phosphines, can be produced on the basis of reaction of cathodic reduction of white phosphorus in the aqueous media under mild conditions.

The M18 Aspartyl Aminopeptidase of the Human Malaria Parasite Plasmodium falciparum

A member of the M18 family of aspartyl aminopeptidases is expressed by all intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum (PfM18AAP), with highest expression levels in rings. Functionally active recombinant enzyme, rPfM18AAP, and native enzyme in cytosolic extracts of malaria parasites are 560-kDa octomers that exhibit optimal activity at neutral pH and require the presence of metal ions to maintain enzymatic activity and stability. Like the human aspartyl aminopeptidase, the exopeptidase activity of PfM18AAP is exclusive to N-terminal acidic amino acids, glutamate and aspartate, making this enzyme of particular interest and suggesting that it may function alongside the malaria cytosolic neutral aminopeptidases in the release of amino acids from host hemoglobin-derived peptides. Whereas immunocytochemical studies using transgenic P. falciparum parasites show that PfM18AAP is expressed in the cytosol, immunoblotting experiments revealed that the enzyme is also trafficked out of the parasite into the surrounding parasitophorous vacuole. Antisense-mediated knockdown of PfM18AAP results in a lethal phenotype as a result of significant intracellular damage and validates this enzyme as a target at which novel antimalarial drugs could be directed. Novel phosphinic derivatives of aspartate and glutamate showed modest inhibition of rPfM18AAP but did not inhibit malaria growth in culture. However, we were able to draw valuable observations concerning the structure-activity relationship of these inhibitors that can be employed in future inhibitor optimization studies.

Enantioselective Organocatalytic Hydrophosphination of α,β‐Unsaturated Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Heterogeneous Pd/C-catalyzed ligand-free Suzuki–Miyaura coupling reaction using aryl boronic esters

Heterogeneous Pd/C-catalyzed Suzuki–Miyaura cross-coupling reaction of aryl boronic esters with aryl bromides was successfully carried out in aqueous media at room temperature without the use of a ligand such as phosphine derivatives.

Synthesis of p-Aminophenyl Aryl H-Phosphinic Acids and Esters via Cross-Coupling Reactions: Elaboration to Phosphinic Acid Pseudopeptide Analogues of Pteroyl Glutamic Acid and Related Antifolates

The synthesis of suitably protected p-aminophenyl H-phosphinic acids and esters from the corresponding para-substituted aryl halides has been accomplished via the Pd-catalyzed cross-coupling reaction of anilinium hypophosphite, either in the absence or presence of a tetraalkyl orthosilicate, to provide the free H-phosphinic acid or the corresponding ester, respectively. Subsequent conjugate addition of either a PIII species or phosphorus anion, generated in situ from either the free H-phosphinic acid or ester, to a 2-methylene glutaric acid ester provided the aryl phosphinic acid analogue of p-aminobenzoyl glutamic acid. Alkylation of these suitably protected p-aminophenyl phosphinic acid esters with a 6-(bromomethyl)pteridine or the corresponding (bromomethyl)pyridopyrmidine, followed by hydrolytic removal of protecting groups, provided the target aryl phosphinic acid analogues of folic acid and related antifolates. Alternatively, for the synthesis of the folate or 5-deazafolate analogues on a slightly larger scale, reductive amination with either N2-acetyl or N2-pivaloyl-6-formylpterin or the corresponding formylpyridopyrmidine and the same suitably protected p-aminophenyl phosphinic acid esters, followed by removal of protecting groups, is preferred. In the course of this research, it was observed that the nucleophilicity of both the aniline nitrogen and various PIII species derived from p-aminophenyl phosphinic acid derivatives is significantly reduced compared to that of the unsubstituted counterpart.

Enantioselective Organocatalytic Hydrophosphination of α,β‐Unsaturated Aldehydes

Keeping it simple: Optically active phosphine derivatives can be obtained in high yields and in up to 99% ee by using simple chiral amines to catalyze the hydrophosphination of α,β-unsaturated alde ...

Palladium-Catalyzed C−P Coupling Reactions between Vinyl Triflates and Phosphine−Boranes: Efficient Access to Vinylphosphine−Boranes

Vinylphosphine-borane complexes are easily synthesized by palladium-catalyzed C-P cross-coupling of vinyl triflates with secondary phosphine-boranes. This method allows the synthesis of phosphine derivatives not always easily accessible by other approaches. The vinylphosphine derivatives are purified by chromatography on silica gel. The versatility of the method is proved by using various triflates and diaryl-, dialkyl- and alkylarylphosphine-borane precursors. Chiral enantiopure phosphine-boranes are synthesized from chiral triflates.

Complexation of Phosphine Ligands with Peracetylated β-Cyclodextrin in Supercritical Carbon Dioxide: Spectroscopic Determination of Equilibrium Constants

The interaction between peracetylated beta-cyclodextrin and several triphenyl phosphine derivatives was studied in supercritical carbon dioxide (scCO2) by UV-visible spectroscopy. The equilibrium constant for a 1:1 complexation reaction was obtained from titration spectra and calculated using two established mathematical models. The values of the equilibrium constants are 1-3 orders of magnitude smaller than those obtained in aqueous solution with analogous phosphines. This is likely due to the absence in scCO2 of the hydrophobic effect, which is replaced by a corresponding, but weaker, CO2-phobic effect. The largest value of Kf was found for complexes of diphenyl(4-adamantylphenyl)phosphine, which is rationalized on the basis of the excellent fit of the phosphine in the cyclodextrin cavity, leading to enhanced host-guest van der Waals interactions. This study can be considered the first step toward the comprehension of the complexation thermodynamics of modified cyclodextrins soluble in scCO2.

Ditertiary phosphine derivatives of the heteronuclear cluster RuOs 3(μ-H) 2(CO) 13

The heteronuclear cluster RuOs 3(μ-H) 2(CO) 13 ( 1) reacted readily with a number of ditertiary phosphines under chemical activation with trimethylamine- N-oxide. The solid-state and solution structures of these derivatives have been examined. Six structural types have been characterized crystallographically, including one in which a phenyl group migrates from the ditertiary phosphine ligand to the metal framework. There are many more isomers present in solution, most of which are rapidly inter-converting via hydride migrations.

Two Isolable Conformers of Dihydropentahelicenediol Derivatives: Stereochemical Property and Its Utility for Asymmetric Reactions

Abstract Conformation of dihydropentahelicenediol 2 and the related compounds was studied. Two isolable conformers, i.e. the diequatorial and the diaxial forms, interconvert only at elevated temperatures, where the equilibrium ratio depends on bulkiness of the substituents attached to the hydroxy groups. The palladium-catalyzed asymmetric allylic substitution was used to test the potential utility of phosphine derivatives, 6eq and 6ax, as chiral ligands.

The Chemistry of Phosphinic and Phosphinous Acid Derivatives Containing t-Butyl Group as a Single Bulky Substituent: Synthetic, Mechanistic and Stereochemical Aspects

Basic synthetic procedures commonly applied for the preparation of racemic and optically active phosphinic and phosphinous acid derivatives containing a t-butyl group as a single bulky substituent are presented. Mechanistic and stereochemical aspects of the presented protocols are discussed. Structural studies, which include the X-ray and vibrational circular dichroism-based determinations of the absolute configuration at the stereogenic phosphorus atom and calculations of conformational equilibria for a few model compounds are also mentioned. The use of the optically active tbutylphenylthiophosphinic acid as a chiral solvating agent is illustrated. Keywords: t-Butylphenylphosphine sulfide, halogenation reaction, iodine oxidation, stereoselectivity, secondary chlorophosphines

Thermodynamic study of lanthanide(iii) complexes with bifunctional monophosphinic acid analogues of H4dota and comparative kinetic study of yttrium(iii) complexes

New bifunctional H(4)dota-like ligands with three acetic acid and one phosphinic acid pendant arms and propionate (H(5)do3ap(PrA)) or 4-aminobenzyl (H(4)do3ap(ABn)) reactive groups bound to the phosphorus atom were investigated. Potentiometric studies showed that the ligands have a similar basicity to the parent H(4)dota and the stability constants of their complexes with sodium(i) and selected lanthanide(III) ions are also similar. Formation and acid-assisted decomplexation kinetics of yttrium(III) complexes with a series of H(4)dota-like ligands (H(4)dota and its phosphinic/phosphonic acid analogues) were studied and the reactions are sensitive to a slight modification of the ligand structure. The (2-carboxyethyl)phosphinic acid derivative H(5)do3ap(PrA) and the phosphonic acid ligand H(5)do3ap form complexes faster than H(4)dota. The most kinetically inert complex is that with H(4)do3ap(ABn). Rates of complexation and decomplexation can depend on the ability to transfer proton(s) outside/inside the complex cavity and, therefore, on the hydrophobicity of the ligands. The results demonstrate that the new bifunctional ligands are suitable for labelling biomolecules with yttrium(iii) radioisotopes for utilization in nuclear medicine.

Staudinger Ligation: A Tool to Monitor Differential Sialic Acid Expression in Glycoproteins

Aberrant sialic acid expression on cell surface glycoproteins is a common occurrence in several disease states. Studies have indicated that enhanced sialyltransferase (ST) activity resulting in hypersialylation is implicated in up-regulation of metastatic potential. Sialic acid presentation can be monitored using cell-surface engineering via the Staudinger ligation. In this study, azide-modified mannose, a sialic acid precursor, was incorporated into the sialic acid salvage pathway. The cell surface sialic acid expression levels were monitored using a Staudinger ligation. A Staudinger ligation is a reaction between azides and a specific phosphine derivative, which are bio-orthogonal functional groups, to yield an amide bond. FLAG-phosphine was used due to the versatility of FLAG epitope in multiple immunochemical techniques. Sialic acid expression in HeLa cells is studied using this technique. The apparent expression levels of sialic acid can be controlled by inhibitors of sialyltransferases or by simply using enzymatic cleavage of sialic acid. The resulting changes in sialic acid presentation was then monitored by probing the FLAG-tag using immunoprecipitation and subsequent western blotting experiments.

Intramolecular Arene Epoxidation by Phosphadioxiranes

Singlet oxygen reacts with binaphthyl phosphine derivatives such as 1,1'-binaphthyl di-tert-butyl phosphine to form the corresponding binaphthyl-2-oxide phosphine oxides. This new intramolecular arene epoxidation reaction proceeds with complete retention of stereochemistry. The binaphthyl-2-oxide di-tert-butyl phosphine oxide undergoes a slow "NIH-rearrangement" to form the corresponding hydroxylated product. A transient phosphadioxirane intermediate has been directly observed by low-temperature NMR. Kinetic analyses show that all of the phosphadioxirane intermediate is converted to product. [reaction: see text]

Anterograde amnesia with hippocampal lesions following glufosinate intoxication

Glufosinate ammonium (GLA), a phosphinic acid derivative of glutamate, is the active ingredient in commercial herbicides. GLA inhibits plant glutamine synthetase, leading to the complete inhibition of ammonia metabolism and photosynthesis. As the use of GLA-containing herbicides has increased, poisoning from incidental and suicidal ingestion has also increased. The neurologic complications of GLA intoxication are characterized by loss of consciousness, convulsions, or memory impairment.1 Unlike in plants, ammonia might not be involved in the toxicity of GLA in mammals2; however, the exact mechanism of GLA toxicity is unknown. Here, we report a patient with GLA poisoning who showed anterograde amnesia with selective bilateral hippocampal lesions and recovered behaviorally after 5 months. A 24-year-old1 man with no previous medical history presented to the emergency department 2 hours after accidentally drinking GLA. He was a college graduate and worked in factory. His friend reported that he probably mistook GLA for milk when he was drunk. Initially, he had recurrent nausea and vomiting. The vital signs were stable. An arterial blood gas determination …

P-Hydrogen-Substituted 1,3,2-Diazaphospholenes: Molecular Hydrides

P-Hydrogen-substituted 1,3,2-diazaphospholenes 1 were prepared by an improved procedure from diazadienes and were characterized by spectroscopy and in one case by X-ray diffraction. A unique hydride-type reactivity of the P-H bonds was documented by extensive reactivity studies. Aldehydes and ketones were readily reduced to diazaphospholene derivatives of the corresponding alcohols, with alkyl-substituted ketones being converted at much lower rates than aldehydes or diaryl ketones. Reactions with the tetrachlorides of group 14 elements proceeded via hydride/chloride metathesis to give either partially chlorinated derivatives EH(n)Cl(4-n) (n = 0-3 for E = C, Si) or HCl and phosphenium salts 16c[ECl3] (for E = Ge, Sn) which were characterized by spectroscopic and X-ray diffraction studies. Tin dichloride was readily reduced to the element. Reactions of 1c with the P-chloro-diazaphospholene 3c and the salt 16c[OTf] allowed the first experimental detection of intermolecular exchange of a hydride, rather than a proton, between phosphine derivatives. Computational studies indicated that the hydride transfer between 1c and the cation 16c involves a transient H-bridged species with bonding properties similar to those of B2H7-. The preference for the formation of these bridged intermediates over P-P bonded phosphenium-phosphine adducts is attributed to the low electrophilicity of the diazaphospholenium cations and characterizes a novel reaction mode for phosphenium ions.

Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer: an17O and1H relaxation study of its Gd(iii) complex

A DTPA-based chelate containing one phosphinate group was conjugated to a generation 5 polyamidoamine (PAMAM) dendrimer via a benzylthiourea linkage. The Gd(III) complex of this novel conjugate has potential as a contrast agent for magnetic resonance imaging (MRI). The chelates bind Gd3+via three nitrogen atoms, four carboxylates and one phosphinate oxygen, and one water molecule completes the inner coordination sphere. The monomer Gd(III) chelates bearing nitrobenzyl and aminobenzyl groups ([Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-) as well as the dendrimeric Gd(III) complex G5-(Gd(DTTAP))63) were studied by multiple-field, variable temperature 17O and 1H NMR. The rate of water exchange is faster than that of [Gd(DTPA)(H2O)]2- and very similar on the two monomeric complexes (8.9 and 8.3 x 10(6) s-1 for [Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-, respectively), while it is decreased on the dendrimeric conjugate (5.0 x 10(6) s-1). The Gd(III) complex of the dendrimer conjugate has a relaxivity of 26.8 mM-1 s-1 at 37 degrees C and 0.47 T (corresponding to 1H Larmor frequency of 20 MHz). Given the contribution of the second sphere water molecules to the overall relaxivity, this value is slightly higher than those reported for similar size dendrimers. The experimental 17O and 1H NMR data were fitted to the Solomon-Bloembergen-Morgan equations extended with a contribution from second coordination sphere water molecules. The rotational dynamics of the dendrimeric conjugate was described in terms of global and local motions with the Lipari-Szabo approach.

Binding of Phosphinate and Phosphonate Inhibitors to Aspartic Proteases: A First-Principles Study

Phosphinate and phosphonate derivatives are potent inhibitors of aspartic proteases (APs). The affinity for the enzyme might be caused by the presence of low barrier hydrogen bonds between the ligand and the catalytic Asp dyad in the cleavage site. We have used density functional theory calculations along with hybrid quantum mechanics/molecular mechanics Car-Parrinello molecular dynamics simulations to investigate the hydrogen-bonding pattern at the binding site of the complexes of human immunodeficiency virus type-1 AP and the eukaryotic endothiapepsin and penicillopepsin. Our calculations are in fair agreement with the NMR data available for endothiapepsin (Coates et al. J. Mol. Biol. 2002, 318, 1405-1415) and show that the most stable active site configuration is the diprotonated, negatively charged form. In the viral complex both protons are located at the catalytic Asp dyad, while in the eukaryotic complexes the proton shared by the closest oxygen atoms is located at the phosphinic/phosphonic group.