Herstellung von 1-Aminoalkan-1,1-diphosphonsäuren

1-Aminoalkane-1,1-diphosphonic acids 1 , 2 or 3 are formed in the reaction of carboxylic acid amide dihalides or carboxylic acid amide hydrohalogenides with phosphorous acid. Phosphorus trihalides plus water may be used in lieu of phosphorous acid in the reaction with carboxylic acid amides. With formamide either aminomethanediphosphonic acid ( 1a ) or 2-oxo-2-hydroxy-5-amino-1,4,2-oxazaphospholidine-3-phosphonic acid ( 5 ) are obtained depending on the reaction conditions.     

Functionally substituted allene phosphonates and their conversion products 1. Reaction of secondary amines with dialkyl esters of 1-methoxy-2,3-alkadiene-2-phosphonic acids

Dialkyl esters of 3-dialkylamino-1,3-alkadiene-2-phosphonic acid have been prepared by the reaction of secondary amines with dialkyl esters of 1-methoxy-2,3-alkadiene-2-phosphonic acid. The presence of a bulky alkyl substituent in the amine or in the initial allenephosphonate hinders the progress of the allene-1,3-diene isomerization.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2736–2740, December, 1989.     

1,3-Dipolar addition of diethyl diazomethylphosphonate onto a CN double bond. Synthesis of triazolinyl and aziridinyl phosphonates

Cycloaddition of diethyl 1-diazomethylphosphonate onto a CN double bond is described. It was found that the reaction of this phosphorus diazomethane with benzylidene-alkyl-amines resulted in the formation of (1-alkyl-5-phenyl-4,5-dihydro-1H-[1,2,3]triazol-4-yl)-phosphonic acid diethyl esters, whereas its reaction with methylene-aryl-amines, generated from the corresponding hexahydro-1,3,5-triazines, led to diethyl esters of (aziridin-2-yl)-phosphonic acid.     

Aziridine-2-phosphonic acid,the valuable synthon for synthesis of 1-amino-2-functionalized ethanephosphonic acids

The ring-opening of aziridine-2-phosphonic acid with a series of nucleophiles was studied. This reaction was found to proceed regioselectively and to provide a good preparative method for the synthesis of phosphonic analogs of various 2-substituted 1-aminoethanecarboxylic acids.     

Synthesis of self-doped conducting polyaniline bearing phosphonic acid

As a self-doped conducting polyaniline bearing phosphonic acid, poly(2-methoxyaniline-5-phosphonic acid) (PMAP) was synthesized via oxidative polymerization of 2-methoxyaniline-5-phosphonic acid. The pyridinium salt of thus-obtained PMAP was water-soluble and its film exhibited conductivity.     

Some transformations in a number of (2-pyridyl)phosphonates

The reaction of sodium diethylphosphite with N-methoxypyridinium methosulfate in a solvent at low temperature makes it possible to obtain diethyl (2-pyridyl)phosphonate in yields up to 75%. The latter was converted to (2-pyridyl)-phosphonic acid dichloride, from which amides, esters, amidochlorides, and (pyridyl)thiophosphonic acid derivatives were obtained.     

Derivatives of 3-thienylphosphonic acid and 1,2-oxaphosphol-3-ene

Alkylsulfenyl chlorides react with 5-methyl-1,3,4-hexatrienyl-3-phosphonic esters giving derivatives of 3-thienylphosphonic acid and 1,2-oxaphosphol-3-ene.     

The synthesis of phosphonic acid and phosphate analogues of glycerol-3-phosphate and related metabolites

A convenient route is described for the preparation of the isosteric phosphonic acid analogue of glycerol-3-phosphate, 3,4-dihydroxybutyl-1-phosphonic acid, in both enantiomeric forms and the racemic modification, starting with readily available materials. The (S)-enantiomer, that of absolute configuration corresponding to that of sn-glycerol-3-phosphate, has been found to be a growth inhibitor of several bacteria at low concentration. The synthetic route described is of particular value as it facilitates the preparation of a series of phosphonic adds and phosphates of related structure, in their enantiomeric forms, which are also of interest for metabolic regulation. These include the 3,4-epoxybutyl-1-phosphonate and a phosphate analogue of glycerol-3-phosphate with the related homodiglyceride. Investigations are continuing in the evaluation of the biological activity of the materials synthesized. A method is also described for the synthesis of the carbon-14 labelled 3-carboxy-3-hydroxybutyl-1-phosphonic acid, an analogue of phosphoglyceric acid known to serve as a substitute for the natural material in several biochemical processes.     

Substituted Esters of Coumarin-3-phosphonic Acid—Linear-Polarized IR-Spectroscopic Elucidation

Correlation between the structure and IR-spectroscopic properties of two halogen and one amino substituted esters of coumarin-3-phosphonic acid has been studied by means of linear-polarized IR-spectroscopy of oriented colloid suspensions in nematic host. The influence of the ester group on the peak positions of the IR-characteristic bands of these derivatives and in particular, on phosphorus group is investigated by a comparison with the data for corresponding coumarin-3-phosphonic acids. Theoretical quantum chemical DFT calculations (B3LYP/6-311++G??) are carried out, thus supporting the experimental assignment of the IR-bands and predicting the electronic structure of all of the compounds studied.     

Synthesis of phosphinic and phosphonic analogs of homoserine

A convenient procedure for the synthesis of 1-amino-3-hydroxypropylphosphinic and -phosphonic acids (analogs of homoserine) was developed. The procedure involves the reaction of salts of phosphinic and phosphonic analogs of S-methylmethionine with AcONa/AcOH followed by hydrolysis.     

Synthese von Aryl-bis(trimethylsilyl)-phosphonsäureestern via Tris-trimethylsilylphosphit – Ein Beitrag zur nickel- katalysierten Michaelis-Arbusov-Reaktion

Synthesis of Aryl-bis(trimethylsilyl)-phosphonic Acid Esters via Tris-trimethylsilylphosphite – a Contribution of the Nickel-catalyzed Michaelis-Arbusov Reaction . The preparation of various aryl-bis(trimethylsilyl)-phosphonic acid esters via P(OSiMe₃)₃ or a mixture of HP(O)(OSiMe₃)₂/P(OSiMe₃)₃/Me₃Si? NH? SiMe₃ in presence of nickel compounds are described. The structures are proved by the ³¹P n.m.r. spectra.     

A novel and simple method for the preparation of (R)- and (S)-pyrrolidine-2-phosphonic acids: phosphonic acid analogues of proline

A simple and convenient method has been developed for the preparation of (R)- and (S)-pyrrolidine-2-phosphonic acids. The thermal reaction of proline with diethyl phosphite in the presence of benzaldehyde gave an N-benzyl derivative of diethyl pyrrolidine-2-phosphonate, which was transformed into two diastereomeric amides by sequential debenzylation and acylation with (+)-dibenzoyl-l-tartaric anhydride. The two diastereomeric amides were separated by column chromatography and the structure of one of them was determined by X-ray crystallographic analysis. Hydrolysis of the amides in the usual manner afforded (R)- and (S)-pyrrolidine-2-phosphonic acids. The advantages of the present method are that it is easy, rapid, and prepares both enantiomers of pyrrolidine-2-phosphonic acids.     

Synthesis of Racemic 1-Aminoindan-1-Phosphonic Acid

Abstract

As part of our studies on the design, synthesis and evaluation of inhibitors of phenylalanine ammonialyase [1–3], we hive investigated the preparation of (±)-1- aminoindan-1-phosphonic acid, a struaural isomer of the strongest in vivo inhibitor [2]. After out unsuccesful amidophosphonylation of l-indanone, we turned our attention to hydrophosphonylrtion of N-(l'-indanylidenc)dipbenylmethylamine obtained from l-indanone and diphenylmethylamine, according to the known procedure for aldehydes [4, 51. Diethyl ± l-(diphenylmethylamino)indan-l-phosphonate has been obtained as shown on the scheme reaction.     

Synthesis and characterization of four metal-organophosphonates with one-, two-, and three-dimensional structures

A series of metal-organic hybrid compounds were synthesized using two new phosphonic acids, pyridyl-4-phosphonic acid and p-xylylenediphosphonic acid (H(2)O(3)PCH(2)C(6)H(4)CH(2)PO(3)H(2)). The phosphonic acid ligands have been synthesized from their corresponding bromides following two different types of reactions. The reaction of pyridyl-4-phosphonic acid with three different divalent metal salts results in the formation of molecular structures of different dimensionality. The reaction of Cu(II) with the phosphonic acid under hydrothermal conditions yields a three-dimensional (3D) open framework structure having the molecular formula [Cu(4)(NC(5)H(4)-PO(3))(4)(H(2)O)(10)] (1). The reactions with Mn(II) and Zn(II) salts with the same phosphonic acid resulted in a two-dimensional layered and a dinuclear compound with molecular formulas [Mn(3)(NC(5)H(4)-PO(3))(4)(H(2)O)(6)(ClO(4))(2)] (2) and [Zn(2)(NHC(5)H(4)-PO(3)H)(2)Cl(4)] (3), respectively. Compound 1 crystallizes in the triclinic crystal system having space group P with structural parameters a = 7.4564(15) Angstrom, b = 9.1845(19) Angstrom, c = 11.582(2) Angstrom, alpha = 100.842(3) degrees, beta = 104.303(3) degrees, gamma = 94.774(3) degrees, and Z = 1. Compound 2 crystallizes in the triclinic crystal system, space group P, with structural parameters a = 7.6871(14) Angstrom, b = 10.576(2) Angstrom, c = 14.470(3)Angstrom, alpha = 81.340(3) degrees, beta = 81.561(3) degrees, gamma = 68.757(3) degrees, and Z = 2, whereas compound 3 crystallizes in a monoclinic crystal system with space group P2(1)/n. The structural parameters are as follows: a = 8.4969 (5) Angstrom, b = 9.3911 (5) Angstrom, c = 12.3779 (6) Angstrom, beta = 90.860(17) degrees, and Z = 4. The pyridylphosphonate ligand shows different ligation behavior toward the three divalent metal ions. On the other hand, p-xylylenediphosphonic acid on reaction with Co(II) formed a 3D compound [Co(2)(O(3)PCH(2)C(6)H(4)CH(2)PO(3))(2)(H(2)O)(2)] (4) with a layered and pillared structure. Compound 4 crystallizes in an orthorhombic crystal system with space group Pnma. The structural parameters are a = 21.744(4) Angstrom, b = 5.6744(10) Angstrom, c = 4.7927(9) Angstrom, and Z = 4.     

Antibacterial Activity of Peptides Related to Alafosfalin. The Effect of Varying the Aminophosphonate Fragment

Abstract

A series of 32 dipeptides containing N-terminal alanine or leu-cine and a variety of racemic 1-aminoalkanephosphonic acids vere prepared by standard procedures and tested for growth inhibition of six bacterial species (Escherichia coli, Klebsiella aerogenes, Serratia mercescens, Staphylococcus aureus, Streptococcus faeca-lis and Bacillus subtilis). The aminophosphonate residues were racemic and included Va1P, LeuP, ProP, PheP, α-methyl-AlaP, Glu-α-P, O-methyl-DOPAP, cyclohexane-1-amino-1-phosphonic acid, t-LeuP, O-acetyl-SerP, and GlyP derivatives RCH(NH₂)PO₃H₂ where R=cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adaman-tyl. N-Ala and N-Leu peptides of racemic AlaP were used as positive control. MIC and IC₅₀ values indicate that the peptides containing 4-amino-4-phosphonobutyric acid (Glu-α-P) and α-methyl-AlaP are potent antibiotics, comparable in activity with LeuAlaP and AlaAlaP (Alafosfalin). Weak activity was observed for peptides of ProP, LeuP, ValP, PheP, cyclohexane-1-amino-1-phosphonic acid and 1-aminocyclopentylmethanephosphonic acid. While the activity of the α-methyl-AlaP peptides may be explained by inhibition of alanine racemase, the mechanism of action of the Glu-α-P peptides remains unknown.     

[2+4] Cycloaddition of tetracyanoethylene with dialkyl esters of 3-dialkylamino-1, 3-alkadiene-2-phosphonic acid

Dialkyl esters of 3-dialkylamino-1,3-alkadiene-2-phosphonic acid undergo [2 + 4] cycloaddition with tetracyanoethylene to give 1-(O,O-dialkylphosphono)-2-dialkylamino-3,3-dimethyl-4,4,5,5-tetracyano-2-cyclohexenes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2843–2845, December, 1989.     

Structural study of phosphorus-containing butadienes. 3. Molecular and crystal structure of the dibromoneopentylglycol and bis-1,3,5-tribromophenyl esters of 3,4-dichloro-1,2-butadiene-2-phosphonic acid

An x-ray structural study of the dibromoneopentylglycol and bis-1,3,5-tribromophenyl esters of 3,4-dichloro-1,2-butadiene-2-phosphonic acid has shown that the nonplanar geometry of the butadiene fragments in the crystals of the compounds studied is determined by a number of shortened intramolecular contacts.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 581–585, March, 1990.The authors thank L. N. Mashlyakovskii for providing the compounds for the x-ray structural study.     

Structure and Physical Properties of Coordination Compounds of 2-Aminoindan-2-Phosphonic Acid with Some D-Electron Elements

Abstract

Many complexes of 1-aminoakylphosphonic acids have been obtained and their structures have been studied [1–3]. On the other hand, 2-aminoindan-2-phosphonic acid (2-AIP), the phosphonic conformationally restricted cyclic analogue of phenylalanine, has been recently obtained [4]. We undertook a study of interaction of cobalt(II), nickel(II), and copper(II) with 2-AIP, to learn how the rigid Iigand structure influences the complexes structure.     

DFT and quantum chemical investigation of molecular properties of substituted pyrrolidinones

The DFT, quantum-chemical calculations and thermodynamics parameters of 1-{2-[(2-hydroxyethyl)thio]ethyl}pyrrolidin-2-one (HTEP); [2-(2-oxo-pyrrolidin-1-yl)-ethyl]-phosphonic acid diethyl ester (EOEP); {[2-(2-oxopyrrolidin-1-yl)ethyl]thio}acetic acid (OETA); (2-pyridin-4-yl-ethyl]thio}acetic acid (PTA) and pyridine (PY) have been calculated with Gaussian 94 and Hybrid B3LYP functional density with 6-31G* basis set. Moreover, the electronic properties such as highest occupied molecular orbital (HOMO), lowest unoccupied orbital (LUMO) energy and molecular densities have been investigated.     

Reaction of dimethylphosphorous acid with 2,5-bis(carbomethoxy)-3,4-diphenylcyclopentadienone

Conclusions The reaction of 2,5-bis(carbomethoxy)-3,4-diphenylcyclopentadienone with dimethyl phosphite, both in the presence of Et₃N and in the absence of catalysts, goes with the formation of the dimethyl esters of 2-oxo-4,5-diphenyl-1,3-dicarbomethoxy-4-cyclopentene- and 2-oxo-4,5-diphenyl-1,3-dicarbomethoxy-3-cyclopentene-1-phosphonic acids. In contrast to alcohols and primary amines, dimethyl phosphite does not form the 1,4-addition products with this acceptor.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1119–1125, May, 1980.