Aminophosphinic Acids Research Articles

Diastereoselective Synthesis of Phosphinic Dipeptide Isosteres: Domino Chirality Transfer during a Stereocontrolled P-Michael Reaction.

A highly diastereoselective P-Michael addition of chiral aminophosphinic acids to achiral acrylates has been developed, leading to phosphinic dipeptide isosteres in high yields and dr of up to >50:1. The method allows for the diastereoselective preparation of target compounds without the need for chiral auxiliaries or P-chiral substrates. A possible mechanistic explanation involves a domino chirality transfer from the aminophosphinic acid to the P center, amplified by a crucial benzhydryl ester group, and then to the α-carbon.

Direct high-performance liquid chromatographic enantioseparation of free α-, β- and γ-aminophosphonic acids employing cinchona-based chiral zwitterionic ion exchangers

We report a chiral high-performance liquid chromatographic enantioseparation method for free α-aminophosphonic, β-aminophosphonic, and γ-aminophosphonic acids, aminohydroxyphosphonic acids, and aromatic aminophosphinic acids with different substitution patterns. Enantioseparation of these synthons was achieved by means of high-performance liquid chromatography on CHIRALPAK ZWIX(+) and ZWIX(-) (cinchona-based chiral zwitterionic ion exchangers) under polar organic chromatographic elution conditions. Mobile phase characteristics such as acid-to-base ratio, type of counterion, and solvent composition were systematically varied in order to investigate their effect on the separation performance and to achieve optimal separation conditions for the set of analytes. Under the optimized conditions, 32 of 37 racemic aminophosphonic acids studied reached baseline separation when we employed a single generic mass-spectrometry-compatible mobile phase, with reversal of the elution order when we used (+) and (-) versions of the chiral stationary phase.

Synthesis, Structure and Application of α, β Dehydro-α-aminophosphonic and α,β-Dehydro-α-aminophosphinic Acid Derivatives

The synthesis of α,β-dehydro-α-aminophosphonic and α,β-dehydro-α-aminophosphinic acid derivatives is discussed. The most important synthetic pathways to the above-mentioned compounds have been divided into four groups depending on the type of bond formed as the last one. The configuration at the C=C double bond can be established based on the specific coupling constants 3JHP and 3JCP for the appropriate Z- and E-stereoisomers. The application of α,β-dehydro-α-aminophosphonates and α,β-dehydro-α- aminophosphinates, particularly in the enantioselective catalytic hydrogenation, is also discussed. Keywords: α -aminophosphinic acids, α -aminophosphonic acids, asymmetric catalytic hydrogenation, α , β -dehydro-α-aminophosphinates, α, β-dehydro-α-aminophosphonates, Michaelis-Arbuzov reaction, Wadsworth-Emmons reaction.

The fluorescence spectroscopic studies on the interaction of novel aminophosphinic acids with bovine serum albumin

Six novel aminomethylphosphinic acids have been synthesized and characterized. The interaction between the aminophosphinic acids and bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The experimental results showed that the fluorescence quenching of BSA by aminophosphinic acids is a result of the formation of aminophosphinic acid–BSA complex; static quenching and non-radiative energy transferring were confirmed to result in the fluorescence quenching. The number of binding sites n, the apparent binding constant KA and the corresponding thermodynamic parameters were calculated at different temperatures. The process of binding of the aminophosphinic acid molecules to BSA was a spontaneous molecular interaction procedure in which entropy increased and Gibbs free energy decreased. Hydrophobic interaction force plays a major role in stabilizing the complex. The effect of aminophosphinic acids on the conformation of BSA was analyzed using synchronous fluorescence spectroscopy.

Synthesis and In-Vitro Antimicrobial Activity of Novel Aminophosphinic Acids Containing Cyclobutane and 1,3-Thiazole

The compounds {[4-(3-methyl-3-aryl(mesityl-phenyl-tetralino)cyclobutyl)-1,3-thiazol-2-yl]amino}(aryl)methyl-phosphinic acids 2a–l were prepared by condensation of 2-amino-4-(3-aryl(mesityl-phenyl-tetralino)-3-methylcyclobutyl) thiazoles 1a–c with various aromatic aldehydes and hypophosphorous acid through a one-pot reaction. The characterizations of these compounds were obtained by elemental analyses, infrared (IR) spectra, and 1H, 13C, and 31P NMR (nuclear magnetic resonance) techniques. The synthesized compounds were tested in vitro against one Gram-positive and two Gram-negative bacterial strains, one mycobacterial strain, and a fungus Candida albicans. Compound 2f showed significant activity against Staphylococcus aureus, whereas the others had no remarkable activity on this strain. Compound 2g was found to be more active than the others against Mycobacterium fortuitum at an MIC (minimum inhibitory concentration) value of 32 μg/mL. The antibacterial and antifungal activities of 2a–l were also compared with various standard drugs.[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Biological Activities. Table S1. Figures S1–S6.]GRAPHICAL ABSTRACT

Aminophosphinic Acids in a Pyridine Series, Part 2: Synthesis of 2-, 3-, and 4-Pyridyl Derivatives of 1-(Benzylamino)-methyl-H-phosphinic Acids

New 2-pyridyl, 3-pyridyl, and 4-pyridyl derivatives of 1-[N-(benzyl)amino]-methyl-H-phosphinic acid were prepared by the addition of bis(trimethylsilyl)phosphonite to the corresponding imines and subsequent methanolysis of the addition products. Treatment of the 2-pyridyl- and 1-(4-pyridyl)-1-(benzylamino)-methyl-H-phosphinic acids with aqueous mineral acids leads to cleavage and formation of the corresponding secondary amines and phosphorous acid (H 3 PO 3 ).

A method of synthesis of phosphinic acids on the basis of hypophosphites: VII. Synthesis of pseudo-γ-aminobutanoyl peptides and other phosphinic analogs of γ-aminobutyric acid

A method of synthesis of pseudo-γ-aminobutanoyl peptides and other phosphinic analogs of γ-aminobutyric acid from hypophosphites is suggested. Silyl phosphonites formed by in situ addition of bis-(trimethylsilyl) hypophosphite to the corresponding α-substituted acrylates, styrene, or vinyl phosphonate used as unsaturated components in the synthesis react in situ with N-(ω-bromoalkyl)phthalimides by an Arbuzov reaction scheme, affording ω-(phthalimido)alkylphosphinic acids possessing β-substituted β-(alkoxycarbonyl)ethyl, β-phenylethyl, or β-(diethoxyphosphinoyl)ethyl substituents. Acid hydrolysis of these reaction products gives the target aminophosphinic acids: phosphinic analogs of γ-aminobutyric acid.

A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics

The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochemistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structures.

Aminophosphinic Acids in a Pyridine Series: Cleavage of Pyridine-2- and Pyridine-4-methyl(amino)phosphinic Acids in Acidic Solutions

The synthesis of a series of new pyridine aminomethylphosphinic acids is described. These compounds were obtained in the reaction of the corresponding pyridine aldehydes with primary amines and with ethyl phenylphosphinate, or methylphosphinate, in the presence of bromotrimethylsilane. In aqueous, strong acid solutions, pyridine aminophosphinic acids were split, forming the phenyl-, or methylphosphonic, acid and the corresponding secondary pyridyl-alkylamines. The kinetics of some observed cleavages were measured, and a mechanism of the cleavage has been proposed.

Synthesis of thiazole aminophosphine oxides, aminophosphonic and aminophosphinic acids and Cu(II) binding abilities of thiazole aminophosphonic acids

A series of new aminophosphine oxides, aminophosphonic and aminophosphinic acids derived from thiazole was synthesized by addition of phosphine oxides or silylated phosphorus esters to the corresponding thiazole aldimines. The thiazole aldimines were obtained from 2-thiazole aldehyde and primary amines by a standard procedure. The corresponding phosphine oxides were obtained by alkylation of diethyl phosphite or ethyl phenylphosphinate with the appropriate Grignard reagents. The silylated phosphorus esters were prepared from trimethyl phosphite and from methyl- or phenylphosphinic ethyl ester by treatment with bromotrimethylsilane. The coordination ability towards Cu(II) ions are described for two obtained aminophosphonate ligands.

A Simple Synthesis of Pyridine Aminophosphinic Acids (V) and Pyridine Aminophosphine Oxides (VIII). The Unusual Cleavage of Pyridylmethyl‐(N‐benzylamino)‐phenylphosphinic Acids and Phosphine Oxides in Acidic Solutions.

A Simple Synthesis of Pyridine Aminophosphinic Acids (V) and Pyridine Aminophosphine Oxides (VIII). The Unusual Cleavage of Pyridylmethyl‐(N‐benzylamino)‐phenylphosphinic Acids and Phosphine Oxides in Acidic Solutions.

A Simple Synthesis of Pyridine Aminophosphinic Acids and Pyridine Aminophosphine Oxides. The Unusual Cleavage of Pyridylmethyl-( N -benzylamino)-phenylphosphinic Acids and Phosphine Oxides in Acidic Solutions

Pyridine aminophosphinic acids were synthesized in reaction of N-(benzyl)-pyridylmethylimines with ethyl phenylphosphinate, in the presence of bromotrimethylsilane. Pyridine aminophosphine oxides were obtained in excellent yields by treatment of the corresponding imines with diphenylphosphine oxide. Among these compounds, the 2-pyridyl and 4-pyridyl derivatives were subject to a simple cleavage in aqueous mineral acid solutions. Products of the cleavages were N-(pyridylmethyl)benzylamines and phenylphosphonic (or diphenylphosphinic) acid, respectively.

Enantiodifferentiation of aminophosphonic and aminophosphinic acids with α- and β-cyclodextrins

Cyclodextrins were used as chiral selectors for the 31P NMR determination of the enantiomeric excess of aminoalkanephosphonic and aminoalkanephosphinic acids. Most of these acids form inclusion complexes with α- and/or β-cyclodextrin and upon increasing the cyclodextrin to aminophosphonic acid molar ratio 31P NMR signals for ( R)- and ( S)-enantiomers separate. ROESY spectra allowed the determination of structures of the inclusion complexes.

Synthesis of New Imidazole Aminophosphonic and Aminophosphinic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective synthesis of phosphinyl peptidomimetics via an asymmetric Michael reaction of phosphinic acids with acrylate derivatives

Asymmetric Michael reaction of phosphinic or aminophosphinic acids with acrylate derivatives afforded phosphinyl dipeptidomimetics in excellent yields (>90%). Chiral induction of substituents at the α-position of acrylate derivatives of Evans oxazolidinone type auxiliaries was obtained in moderate to excellent diastereomeric and enantiomeric excesses (50–98%). Pure diastereomers and enantiomers of phosphinyl dipeptidomimetics 16– 19 were also successfully separated by HPLC.

ChemInform Abstract: Naturally Occurring Aminophosphonic and Aminophosphinic Acids

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Structures of Metal Complexes with Anions of Di(hydroxymethyl)phosphinic and Di(chloromethyl)phosphinic Acids

This paper considers the structural features of complexes containing Ag(I), 3dmetals (Cu and Ni), and rare-earth elements (REE) such as La, Nd, Er, and Lu, alkaline-earth (Sr) or alkaline (Li, Na) metals with anions of di(hydroxymethyl)phosphinic (L1) or di(chloromethyl)phosphinic (L2) acids with a general formula RR"PO–2, where R = R" = OH and Cl for L1and L2, respectively. Different patterns of coordination between organophosphorus acids and different metals (four for each L1and L2) are described. Structures of copper(II) complexes with L1and L2were compared with those of Cu(II) with dialkyl- and diaryl-substituted monophosphonic and aminophosphinic acids.

ChemInform Abstract: Asymmetric Synthesis of Aminophosphonic and Aminophosphinic Acids

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

NMR‐controlled titrations: characterizing aminophosphonates and related structures

Aminophosphonic acids, aminophosphinic acids, and aminophosphonous acids give rise to interesting protonation and metal complex formation equilibria, which can be monitored by potentiometric and NMR spectroscopic methods. A hyphenated technique referred to as NMR-controlled titrations or titration-dependent NMR spectroscopy has been introduced. Vicinal and geminal bisphosphonic acids have also been characterized by this method. Gradients (titration shifts) in chemical shifts and coupling constants were used to elucidate the structures of the protolytic species. Microscopic dissociation equilibria have also been studied by NMR-controlled titrations for glufosinate and 4-aminophenylphosphonic acid. Some comments are made on the UV-vis-controlled titration of the latter compound. Novel, advanced algorithms were used to estimate the error of analytical and NMR parameters, such as pK values, molar fractions, and ion-specific chemical shifts, describing the aminophosphonate ligands in each protonation form. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:562–582, 2000

NMR-controlled titrations: characterizing aminophosphonates and related structures

Aminophosphonic acids, aminophosphinic acids, and aminophosphonous acids give rise to interesting protonation and metal complex formation equilibria, which can be monitored by potentiometric and NMR spectroscopic methods. A hyphenated technique referred to as NMR-controlled titrations or titration-dependent NMR spectroscopy has been introduced. Vicinal and geminal bisphosphonic acids have also been characterized by this method. Gradients (titration shifts) in chemical shifts and coupling constants were used to elucidate the structures of the protolytic species. Microscopic dissociation equilibria have also been studied by NMR-controlled titrations for glufosinate and 4-aminophenylphosphonic acid. Some comments are made on the UV-vis-controlled titration of the latter compound. Novel, advanced algorithms were used to estimate the error of analytical and NMR parameters, such as pK values, molar fractions, and ion-specific chemical shifts, describing the aminophosphonate ligands in each protonation form. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:562–582, 2000