Phosphonate Monoester Research Articles

ChemInform Abstract: Rhodium‐Catalyzed Oxidative C—H Activation/Cyclization for the Synthesis of Phosphaisocoumarins and Phosphorous 2‐Pyrones.

AbstractRhodium‐catalyzed cyclizations of phosphinic acids and phosphonic monoesters with alkynes are developed.

Metal–organic frameworks with improved moisture stability based on a phosphonate monoester: effect of auxiliary N-donor ligands on framework dimensionality

A series of metal–organic frameworks (MOFs) with improved moisture stability based on a phosphonate monoester, featuring 1D chains, 2D layers and 3D networks, have been obtained in the presence of auxiliary N-donor ligands.

Palladium(II)-Catalyzed Ortho-Arylation of Benzylic Phosphonic Monoesters Using Potassium Aryltrifluoroborates

The new monophosphonic acid directing group was successfully utilized in the Pd (II)-catalyzed ortho-arylation of benzylic phosphonic monoesters using potassium aryltrifluoroborates. A wide range of benzylic phosphonic monoesters underwent clean ortho-arylation in high yields, and excellent functional group tolerance was also observed.

Rhodium‐Catalyzed Oxidative C–H Activation/Cyclization for the Synthesis of Phosphaisocoumarins and Phosphorous 2‐Pyrones

Rhodium-catalyzed cyclization of phosphinic acids and phosphonic monoesters with alkynes has been developed. The oxidative annulation proceeds with complete conversion of phosphinic acid derivatives and allowed the atom-economic preparation of useful phosphaisocoumarins with high yield and selectivity. The reaction is tolerant of extensive substitution on the phosphinic acid, phosphonic monoester and alkyne, including halides, ketone, and hydroxyl groups as substituents. Furthermore, we found that alkenylphosphonic monoesters proceed to give a wide range of phosphorus 2-pyrones through oxidative annulation with alkynes. Mechanistic studies revealed that C-H bond metalation was the rate-limiting step.

Ortho-(methylsulfanyl)phenylphosphonates and derivatives: Synthesis and applications as mono- or bidentate ligands for the preparation of platinum complexes

The preparation of six phenylphosphonates (and phosphonic acid derivatives) bearing a sulfur group in ortho position was accomplished via either a [1,3]- or a [1,4]-sigmatropic rearrangement. Their complexation with different platinum sources has been studied and the new platinum complexes obtained were characterized by NMR spectroscopy (1H, 13C, 31P and 195Pt). Three runs of experiments were performed. The first was the reaction of ligands 1 and 2 bearing one sulfide and a phosphonate diester functions with potassium tetrachloroplatinate. In the obtained complexes, two molecules of ligand chelate the metal only by the sulfur atom. We were able to observe by 195Pt and 31P NMR spectroscopy the trans to cis rearrangement of a dichloro-methyl-(o-phosphorylbenzyl)sulfide platinum(II) complex upon time, leading to two new species, which are diastereomers of the cis-complex. The second set of experiments involved ligands 1, 2 and 3 bearing one sulfide or sulfoxide and a phosphonate diester moieties, cisplatin and one equivalent of silver nitrate. In the resulting complexes the platinum is coordinated by the sulfur atom of one molecule of ligand. In the third run, the reaction between ligands 4, 5, and 6 bearing one sulfide or sulfoxide and one phosphonic acid or one phosphonic monoester group and the cisplatin diaqua form led to O,S–Pt chelates.

One-pot synthesis of symmetrical P1,P2-dinucleoside-5′-diphosphates from nucleoside-5′-H-phosphonates: mechanistic insights into reaction path

Six symmetrical P 1 , P 2 -dinucleoside-5′-diphosphates (Np 2 Ns) have been synthesized from nucleoside-5′- H -phosphonate monoesters via a one-pot reaction in high yields. The key sequential hydrolysis protocol was developed based on the observation of reactive P 1 , P 2 , P 3 -trinucleoside-5′-triphosphate intermediate on 31 P NMR.

Palladium(II)-Catalyzed ortho-Olefination of Benzylic Phosphonic Monoesters

The new monophosphonic acid directing group is successfully utilized in the Pd(II)-catalyzed ortho-olefination of benzylic phosphonic monoesters and offers further development of other phosphoryl-related directing groups in the transition-metal-catalyzed C-H activations.

Harnessing Promiscuity Patterns to Map Evolution in the Alkaline Phosphatase Superfamily

In the past 30 yeas scientists have demonstrated that many enzymes are capable of promiscuous catalytic activity, in which one enzyme catalyses the turnover of chemically distinct substrates. It has been suggested that such promiscuity can play an important role in the evolution of enzyme function. This phenomenon is particularly pronounced in the alkaline phosphatase superfamily, in which the native reaction for one member of the superfamily is often a promiscuous side reaction for another. Moreover, despite the similarity of the substrates involved, the reactions catalysed (cleavage of P-O and S-O bonds) proceed with very different solvation and protonation requirements. We present here a detailed study of the promiscuous catalytic activity of three evolutionarily related but structurally different members of this superfamily: an arylsulfatase from Pseudonomas aeruginosa (PAS) and two phosphonate monoester hydrolases (PMH) from Rhizobium leguminosarum and Burkholderia caryophylli. The latter enzymes are particularly interesting due to the fact that, in addition to their broad promiscuity, they are also capable of catalysing a xenobiotic substrate for which no natural catalyst is known. We demonstrate that subtle changes in active site residues can have a significant impact on mechanism. However, despite such mechanistic variation, the promiscuity simply arises out of the ability of the non-native substrates to exploit the pre-existing electrostatic pre-organization of the active site towards the native substrate. We believe this provides an example of chemically-driven protein evolution within an enzyme superfamily.

Enhancing Water Stability of Metal–Organic Frameworks via Phosphonate Monoester Linkers

A new porous metal-organic framework (MOF), barium tetraethyl-1,3,6,8-pyrenetetraphosphonate (CALF-25), which contains a new phosphonate monoester ligand, was synthesized through a hydrothermal method. The MOF is a three-dimensional structure containing 4.6 Å × 3.9 Å rectangular one-dimensional pores lined with the ethyl ester groups from the ligand. The presence of the ethyl ester groups makes the pores hydrophobic in nature, as determined by the low heats of adsorption of CH(4), CO(2), and H(2)O (14.5, 23.9, and 45 kJ mol(-1), respectively) despite the polar and acidic barium phosphonate ester backbone. The ethyl ester groups within the pores also protect CALF-25 from decomposition by water vapor, with crystallinity and porosity being retained after exposure to harsh humid conditions (90% relative humidity at 353 K). The use of phosphonate esters as linkers for the construction of MOFs provides a method to protect hydrolytically susceptible coordination backbones through kinetic blocking.

ChemInform Abstract: One‐Pot Synthesis of Phosphate Diesters and Phosphonate Monoesters via a Combination of Microwave‐CCl3—Pyridine Coupling Conditions.

ChemInformVolume 43, Issue 17 Organoelement Compounds ChemInform Abstract: One-Pot Synthesis of Phosphate Diesters and Phosphonate Monoesters via a Combination of Microwave-CCl3—Pyridine Coupling Conditions. Hao-Wei Shih, Hao-Wei Shih Genom. Res. Cent., Acad. Sin., Taipei 11529, TaiwanSearch for more papers by this authorKuo-Ting Chen, Kuo-Ting Chen Genom. Res. Cent., Acad. Sin., Taipei 11529, TaiwanSearch for more papers by this authorWei-Chieh Cheng, Wei-Chieh Cheng Genom. Res. Cent., Acad. Sin., Taipei 11529, TaiwanSearch for more papers by this author Hao-Wei Shih, Hao-Wei Shih Genom. Res. Cent., Acad. Sin., Taipei 11529, TaiwanSearch for more papers by this authorKuo-Ting Chen, Kuo-Ting Chen Genom. Res. Cent., Acad. Sin., Taipei 11529, TaiwanSearch for more papers by this authorWei-Chieh Cheng, Wei-Chieh Cheng Genom. Res. Cent., Acad. Sin., Taipei 11529, TaiwanSearch for more papers by this author First published: 29 March 2012 https://doi.org/10.1002/chin.201217189Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume43, Issue17April 24, 2012 RelatedInformation

Phosphonate Monoesters as Carboxylate-like Linkers for Metal Organic Frameworks

Bidentate phosphonate monoesters are analogues of popular dicarboxylate linkers in MOFs, but with an alkoxy tether close to the coordinating site. Herein, we report 3-D MOF materials based upon phosphonate monoester linkers. Cu(1,4-benzenediphosphonate bis(monoalkyl ester), CuBDPR, with an ethyl tether is nonporous; however, the methyl tether generates an isomorphous framework that is porous and captures CO(2) with a high isosteric heat of adsorption of 45 kJ mol(-1). Computational modeling reveals that the CO(2) uptake is extremely sensitive both to the flexing of the structure and to the orientation of the alkyl tether.

One-pot synthesis of phosphate diesters and phosphonate monoesters via a combination of microwave-CCl3CN–pyridine coupling conditions

Simple and convenient one-pot synthesis of a phosphorus–oxygen bond in phosphate diesters and phosphonate monoesters using trichloroacetonitrile as an activating agent and pyridine as a solvent under microwave irradiation conditions was described. This method is useful for the preparation of various biologically interesting glycophospholipids and also phosphate diesters or phosphonate monoesters containing diverse moieties such as alkyl, prenyl, and benzyl substituents.

Separation and determination of 241Am in urine samples from radiation workers using PC88-A and alpha spectrometry

Bioassay technique is used for the estimation of actinides present in the body based on their excretion rate through body fluids. For occupational radiation workers urine assay is the preferred method for monitoring of chronic internal exposure. Determination of low concentrations of actinides such as plutonium, americium and uranium at low level of mBq in urine by alpha spectrometry requires pre-concentration of large volumes of urine. This article deals with standardization of analytical method for the determination of 241Am isotope in urine samples using Extraction Chromatography (EC) and 243Am tracer for radiochemical recovery. The method involves oxidation of urine followed by co-precipitation of americium along with calcium phosphate. This precipitate after treatment is further subjected to calcium oxalate co-precipitation. Separation of Am was carried out by EC column prepared by PC88-A (2-ethyl hexyl phosphonic acid 2-ethyl hexyl monoester) adsorbed on microporous resin XAD-7 (PC88A-XAD7). Am-fraction was electro-deposited and activity estimated using tracer recovery by alpha spectrometer. Ten routine urine samples of radiation workers were analyzed and consistent radiochemical recovery was obtained in the range 44–60% with a mean and standard deviation of 51 and 4.7% respectively.

An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

We report a catalytically promiscuous enzyme able to efficiently promote the hydrolysis of six different substrate classes. Originally assigned as a phosphonate monoester hydrolase (PMH) this enzyme exhibits substantial second-order rate accelerations ((k(cat)/K(M))/k(w)), ranging from 10(7) to as high as 10(19), for the hydrolyses of phosphate mono-, di-, and triesters, phosphonate monoesters, sulfate monoesters, and sulfonate monoesters. This substrate collection encompasses a range of substrate charges between 0 and -2, transition states of a different nature, and involves attack at two different reaction centers (P and S). Intrinsic reactivities (half-lives) range from 200 days to 10(5) years under near neutrality. The substantial rate accelerations for a set of relatively difficult reactions suggest that efficient catalysis is not necessarily limited to efficient stabilization of just one transition state. The crystal structure of PMH identifies it as a member of the alkaline phosphatase superfamily. PMH encompasses four of the native activities previously observed in this superfamily and extends its repertoire by two further activities, one of which, sulfonate monoesterase, has not been observed previously for a natural enzyme. PMH is thus one of the most promiscuous hydrolases described to date. The functional links between superfamily activities can be presumed to have played a role in functional evolution by gene duplication.

Efficient Synthesis of Highly Active Phospha‐Isosteres of the Influenza Neuraminidase Inhibitor Oseltamivir

With a Hunsdiecker-Barton iododecarboxylation strategy, we converted the carboxylate group of the oseltamivir precursor into exemplary phosphonate monoesters. In all cases, K(i) values towards influenza virus sialidase remained in the sub-nanomolar range. We have thus made valuable structural space available for the design of novel oseltamivir-based tools for influenza virus research.

Lanthanide(III) Complexes of Phosphorus Acid Analogues of H4DOTA as Model Compounds for the Evaluation of the Second‐Sphere Hydration

AbstractFive DOTA‐like ligands lacking a water molecule in the first coordination sphere of their GdIII complexes, namely the phosphinates H4DOTPH, H4DOTPhm and H4DOTPEt, and the phosphonate monoesters H4DOTPOEt and H4DOTPOBu, were synthesized with the aim of exploring the influence of the second hydration sphere on the relaxivity of GdIII complexes. The H4DOTPH, H4DOTPhm and H4DOTPOEt ligands and their LnIII complexes were characterized by potentiometry and time‐resolved luminescence; the GdIII complexes are thermodynamically much less stable than that of H4DOTA, and no water is coordinated in the inner sphere. The crystal structures of the free ligand H4DOTPOEt and of the GdIII complexes of H4DOTPH and H4DOTPOEt were determined by X‐ray diffraction. The complexes have the expected octadentate coordination mode with an N4O4 arrangement; no water molecule is bound to the GdIII ion. Information on the structures of the LnIII complexes of all five ligands in aqueous solution were obtained from 1H and 31P NMR spectra. The NMR spectra of the [Ln(DOTPhm)]– and [Ln(DOTPEt)]– complexes show that these compounds have a clear preference for a specific arrangement of phosphorus atoms which gives rise to the symmetrical RRRR (or SSSS) isomer. However, many diastereoisomers were observed for all other complexes. LnIII‐induced 17O NMR shift data reveal that the spatial location of the second‐sphere water molecules for the two groups of complexes differs. The parameters governing the effect of the second hydration sphere on the relaxivity of the GdIII complexes of all ligands were evaluated by EPR, variable‐temperature 17O NMR spectroscopy and 1H NMRD relaxometry. The presence of second‐sphere water molecules is clearly confirmed, depending on the character of the pendant arms. As the relaxivity does not depend significantly on the nature of the phosphorus substituents and/or on the isomerism present in solution, the second‐sphere water molecules should be located close to the phosphorus–oxygen atoms.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

ChemInform Abstract: Preparation of Halo Enol Phostones by Reaction of Acetylenic Phosphonate Monoesters with (Bis‐collidine)halo Hexafluorophosphate.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A New Member of the Alkaline Phosphatase Superfamily with a Formylglycine Nucleophile: Structural and Kinetic Characterisation of a Phosphonate Monoester Hydrolase/Phosphodiesterase from Rhizobium leguminosarum

The alkaline phosphatase superfamily comprises a large number of hydrolytic metalloenzymes such as phosphatases and sulfatases. We have characterised a new member of this superfamily, a phosphonate monoester hydrolase/phosphodiesterase from Rhizobium leguminosarum (RlPMH) both structurally and kinetically. The 1.42 Å crystal structure shows structural homology to arylsulfatases with conservation of the core α/β-fold, the mononuclear active site and most of the active-site residues. Sulfatases use a unique formylglycine nucleophile, formed by posttranslational modification of a cysteine/serine embedded in a signature sequence (C/S)XPXR. We provide mass spectrometric and mutational evidence that RlPMH is the first non-sulfatase enzyme shown to use a formylglycine as the catalytic nucleophile. RlPMH hydrolyses phosphonate monoesters and phosphate diesters with similar efficiency. Burst kinetics suggest that substrate hydrolysis proceeds via a double-displacement mechanism. Kinetic characterisation of active-site mutations establishes the catalytic contributions of individual residues. A mechanism for substrate hydrolysis is proposed on the basis of the kinetic data and structural comparisons with E. coli alkaline phosphatase and Pseudomonas aeruginosa arylsulfatase. RlPMH represents a further example of conservation of the overall structure and mechanism within the alkaline phosphatase superfamily.

Preparation of halo enol phostones by reaction of acetylenic phosphonate monoesters with (bis-collidine)halo hexafluorophosphate

Reaction of non-conjugated acetylenic phosphonate monoesters with (bis-collidine) bromo and iodo hexafluorophosphates was found to lead to the formation of halo enol phostones. Depending on the size of the heterocyclic compounds formed (6–8-membered compounds), endo or a mixture of endo and exo cyclization products were obtained.

Chemical and biological evaluation of 153Sm and 166Ho complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid monoethylester) (H4dotpOEt)

The novel methylphosphonic acid monoethylester (H4dotpOEt) has been synthesized and characterized and their complexes with Sm(III) and Ho(III) ions were studied. Dissociation constants of the ligand are lower than those of H4dota. The stability constants of the Ln(III)-H4dotpOEt complexes are surprisingly much lower that those of H4dota (H4dota=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) probably due to a lower coordination ability of the phosphonate monoester groups. Acid-assisted decomplexation studies have shown that both complexes are less kinetically inert than the H4dota complexes, but still much more inert than complexes of open-chain ligands. Nevertheless, the synthesis of 153Sm and 166Ho complexes with this ligand led to stable complexes both in vitro and in vivo. A very low binding of these complexes to hydroxyapatite (HA) and calcified tissues was observed confirming the assumption that a fully ionized phosphonate group(s) is necessary for a strong bone affinity. Both complexes show similar behaviour in vivo and, in general, follow the biodistribution trend of the H4dota complexes with the same metals.