Diphenyl Phosphonate Research Articles

Chemical and plasma hydrolyses of a diphenyl α-aminomethyl phosphonate prodrug inhibitor of neutral endopeptidase 24.11

The rate and product selectivity of the hydrolysis of CGS 25462 ( 1 ), an orally active diphenyl phosphonate prodrug of a potent neutral endopeptidase 24.11 inhibitor, has been studied in acidic and basic solutions and in the plasma of four species. While the chemical hydrolysis of 1 generally afforded the monophenyl phosphonate intermediate 2 , further conversion to the bioactive phosphonic acid 3 occurred in bicarbonate solution. Concerning the generation of 3 from 1 in plasma, the data are consistent with the involvement of a biological catalysis, which may also apply in the hydrolysis of the prodrug in vivo.

ChemInform Abstract: A Convenient Synthesis of N‐Protected Diphenyl Phosphonate Ester Analogues of Ornithine, Lysine, and Homolysine.

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A convenient synthesis of N-protected diphenyl phosphonate ester analogues of ornithine, lysine and homolysine.

Abstract A 3-step synthesis to the title compounds has been developed which provides them differentially protected at nitrogen. These could then be selectively deprotected using hydrazine hydrate or hydrogenolysis over Pd/C.

The Synthesis of Phosphonate Analogues of Amino Acids and Peptides

Abstract Diphenyl phosphonate ester analogues of phenylalanine and peptides derived from these have been prepared and are shown to specifically inhibit chymotrypsin. Phosphonate isosters of serine and tyrosine phosphates appropriately protected for use in peptide synthesis have been prepared.

Synthesis of polyamic acid di‐tert‐butyl esters by direct polycondensation of di‐tert‐butyl esters of tetracarboxylic acids with diamines using diphenyl (2,3‐dihydro‐2‐thioxo‐3‐benzoxazolyl)phosphonate

AbstractThe direct polycondensation using the activating agent diphenyl (2,3‐dihydro‐2‐thioxo‐3‐benzoxazolyl)phosphonate (1) was successfully applied to the synthesis of polyamic acid tert‐butyl esters, which readily undergo AAL 1 type acid‐catalyzed deesterification. Polycondensations of di‐tert‐butyl esters of tetracarboxylic acids with diamines were conducted in N‐methyl‐2‐pyrrolidone in the presence of triethylamine at room temperature, producing poly(amide‐ester)s with inherent viscosities up to 1,1 dL · g−1. The effects of various factors, such as solvent, amount of solvent, and amount of the activating agent, were studied. The poly(amide‐ester)s are readily soluble in dipolar aprotic solvents and can be cast into uniform films from their solutions. Thermogravimetry of the polymers showed that the deesterification and imidization occur around 150–200°C, giving polyimides.

Synthesis of ordered polyamides by direct polycondensation. 3

Ordered (head-to-tail) polyamides with inherent viscosities up to 0.22 dL/gwere prepared by the direct polycondensation of a symmetric monomer, succinic anhydride, with a nonsymmetric monomer, 2-(4-aininophenyl)ethylainine, or a pair of two symmetric monomers, 4,4'-oxydianiline and m-xylylenediainine, using the activating agent diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate. The microstructure of the polyamides was investigated by 13 C NMR and the model reaction was studied in detail to demonstrate the feasability of ordered polyamidation

Diphenyl (2,3-Dihydro-2-thioxo-3-benzoxazolyl)phosphonate: A New, Reactive Condensing Agent for the Synthesis of Amides, Esters, Peptides, and β-Lactams via Condensation

Abstract Diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate (1) prepared from 2-benzoxazolethiol and diphenyl phosphorochloridate was proved to be a very useful condensing agent. A variety of amides, esters, and dipeptides were obtained in excellent yields. Furthermore, this reagent was successfully applied to the synthesis of β-lactams from β-amino acids.

The preparation and reactions of protected glyphosate imidate, thioimidate, and thiono esters from N-[diphenoxyphosphinylmethyl]glycinonitrile: Comparative reactivities of activated carboxylate versus phosphonate esters

The highly efficient syntheses of novel protected glyphosate imidate, thioimidate, and thiono ester derivatives are described starting from N-[diphenoxyphosphinylmethyl]glycinonitrile 3b. The scope, utility and limitations in using each of these activated carboxylate functionalities for further transformations to new “masked” heterocyclic derivatives are defined. While the solution stability of the imidate and thioimidate series limited the synthetic application of these species, the corresponding thiono ester derivatives were valuable synthetic intermediates, providing a short, efficient route to the first glyphosate derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole ring systems in place of the carboxylate group. These thiono esters thus undergo selective nucleophilic addition at this activated carboxylate center, while retaining the reactive diphenyl phosphonate moiety.

Mixed metal vinyl stabilizer synergism. III: Reactions of mixed metals and phosphites with a model compound

AbstractIn the absence of mixed metal carboxylates, triaryl phosphites react rapidly with a model allylic compound for degrading vinyl, cinnamyl chloride, to yield phosphonium salts. On heating, these appear to yield allylidene phosphoranes by 1,1 elimination of HCl, with subsequent rearrangement to diphenyl phosphonates. With aryl alkyl phosphites, the phosphonium chloride intermediate undergoes rapid Arbusov rearrangement to the diphenyl phosphonate, eliminating alkyl chloride (or corresponding olefin). In the presence of zinc or cadmium carboxylates, Arbusov rearrangement is intercepted and chloride is transferred instead to the metal, forming the alkyl ester. The observed reaction paths appear to yield insight into the question of which phosphites are optimum for particular metal carboxylate blends and ratios in vinyl stabilizers, and into the related topic of which types of other additives are inappropriate.

Dipeptide Derivatives with a Phosphonate Instead of Carboxylate Terminus by C‐Alkylation of Protected (Decarboxy‐dipeptidyl)phosphonates

AbstractZ‐Protected diphenyl (decarboxy‐dipeptidyl)phosphonates 5a‐c with a (decarboxysarcosinyl)phosphonate moiety are prepared from Z‐L‐alanine (1a). Z‐L‐valine (1b), and Z‐L‐phenylalanine (1c) by the following series of steps: coupling with methyl sarcosinate (→2a–c), saponification (→3a–c), Hofer‐Moest oxidative decarboxyiation by electrolysis in MeOH (→4a–c), and Arbuzov reaction with P(OPh)3/TiCl4 (Scheme 3). Double deprotonation and alkylation lead to non‐stereoselective incorporation of side chains next to the phosphonate group (products of type 6–8, nine examples, see Scheme 4). In the cases of 6a–c and 8c, the diastereoisomers could be separated and the configuration of the newly formed stereogenic center deduced. We assign the L,D‐configuration to the diastereoisomers for which the 31P‐NMR signal appears at higher field.

Irreversible inhibition of serine proteases by peptide derivatives of (.alpha.-aminoalkyl)phosphonate diphenyl esters

Peptidyl derivatives of diphenyl (alpha-aminoalkyl)phosphonates have been synthesized and are effective and specific inhibitors of serine proteases at low concentrations. Z-PheP(OPh)2 irreversibly reacts with chymotrypsin (kobsd/[I] = 1200 M-1 s-1) and does not react with two elastases. The best inhibitor for most chymotrypsin-like enzymes including bovine chymotrypsin, cathepsin G, and rat mast cell protease II is the tripeptide Suc-Val-Pro-PheP(OPh)2 which corresponds to the sequence of an excellent p-nitroanilide substrate for several chymases. The valine derivative Z-ValP(OPh)2 is specific for elastases and reacts with human leukocyte elastase (HLE, 280 M-1 s-1) but not with chymotrypsin. The tripeptide Boc-Val-Pro-ValP(OPh)2, which has a sequence found in a good trifluoromethyl ketone inhibitor of HLE, is the best inhibitor for HLE (kobsd/[I] = 27,000 M-1 s-1) and porcine pancreatic elastase (PPE, kobsd/[I] = 11,000 M-1 s-1). The rates of inactivation of chymotrypsin by MeO-Suc-Ala-Ala-Pro-PheP(OPh)2 and PPE and HLE by MeO-Suc-Ala-Ala-Pro-ValP(OPh)2 were decreased 2-5-fold in the presence of the corresponding substrate, which demonstrates active site involvement. Only one of two diastereomers of Suc-Val-Pro-PheP(OPh)2 reacts with chymotrypsin (146,000 M-1 s-1), and the enzyme-inhibitor complex had one broad signal at 25.98 ppm in the 31P NMR spectrum corresponding to the Ser-195 phosphonate ester. Phosphonylated serine proteases are extremely stable since the half-time for reactivation was greater than 48 h for the inhibited elastases and 7.5-26 h for chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)

A structural study of 3- and 4-iodosylbenzoic acids, 3- and 4-iodylbenzoic acids, and their sodium salts

The 13C NMR, IR, and UV spectra of 3- and 4-iodobenzoic, 3- and 4-iodosylbenzoic, and 3- and 4-iodylbenzoic acids and their sodium salts have been measured and compared with those of the corresponding 2-isomers. Kinetic data for the catalytic microemulsion hydrolysis of 4-nitrophenyl diphenyl phosphonate in the presence of the iodosyl and iodyl compounds have been obtained. Catalytic efficiency of the 3- and 4-substituted isomers are measured to be three to six orders of magnitude less effective than the corresponding 2-substituted isomers. Possible structural configurations are suggested and discussed.

Synthesis of a non-isosteric, isopolar monophosphonate analogue of β- d-fructose 2,6-bisphosphate

A synthesis of the non-isosteric, isopolar glyculosylmonophosphonate analogue 6 of β- d-fructose 2,6-bisphosphate ( 1) is described. Treatment of 2- O-acetyl-1,3,4,6-tetra- O-benzyl-α,β- d-fructofuranose ( 8) with trialkyl or triaryl phosphite in the presence of trimethylsilyl trifluoromethanesulfonate gave the glyculosylphosphonates 9, 11, and 13, respectively, with the 2,3- cis-configuration, as the major anomers, and 10, 12, and 14, respectively, as the minor anomers. The structures of 9–14 were deduced from the 1H-, 13C-, and 31P-n.m.r. spectra, which indicated a 4 T 3 conformation for each conformer. Selective acetolysis of 13 gave diphenyl (6- O-acetyl-1,3,4-tri- O-benzyl-β- d-fructofuranosyl)phosphonate ( 15). Base-catalysed transesterification of 15 gave diphenyl (1,3,4-tri- O-benzyl-β- d-fructofuranosyl)phosphonate ( 17), which cyclised easily to give the phostone 18. Phosphorylation of 17 followed by hydrogenolysis gave the β- d-fructofuranosyl-phosphonate 6 characterised as the cyclohexylammonium salt 20.

Diphenyl phosphonate ester cleavage catalyzed by hydrophobic ammonium ions

The basic hydrolysis of diphenyl [1-(N-benzyloxy-carbonylalanyl)-3-methyl]butylphosphonate have been studied in various cationic micelles. The kinetics of the reactions in buffered solutions and dilute sodium hydroxide solutions are compared.

Transesterification of Diphenyl Phosphonates using the Potassium Fluoride/Crown Ether/Alcohol System; Part 1. Transesterification of Diphenyl 1-(Benzyloxycarbonylamino)-alkanephosphonates

Transesterification of Diphenyl Phosphonates using the Potassium Fluoride/Crown Ether/Alcohol System; Part 1. Transesterification of Diphenyl 1-(Benzyloxycarbonylamino)-alkanephosphonates

Transesterification of Diphenyl Phosphonates using the Potassium Fluoride/Crown Ether/Alcohol System; Part 2. The Use of Diphenyl 1-Aminoalkanephosphonates in Phosphonopeptide Synthesis

Transesterification of Diphenyl Phosphonates using the Potassium Fluoride/Crown Ether/Alcohol System; Part 2. The Use of Diphenyl 1-Aminoalkanephosphonates in Phosphonopeptide Synthesis

Separation of Metals on Sulfonated Diphenyl Phosphonate–Formaldehyde Resin in HCl–Organic Solvent Systems

Abstract The distribution coefficients of several metal ions have been measured on sulfonated diphenyl phosphonate–formaldehyde resin in HCl–water miscible organic solvent solutions. Differences in the distribution coefficients are large enough to develop multicomponent separations. Particularly in HCl-propanone systems the separation of a complex mixture, Cd(II)–Zn(II)–Pb(II)–Cu(II)–Co(II)–Mn(II)–Mg(II), can be carried out chromatographically by sequential elution.

Adsorption of the Chromate Ion on Cured Diphenyl Phosphonate-Aldehyde Resins

Abstract The adsorption of the chromate ion on cured diphenyl phosphonate-aldehyde resins has been investigated. Phosphorus-containing novolak type resins, obtained from the reaction of diphenyl phosphonate with aldehydes have been cured with additional hexamethylenetetramine. The adsorption of the chromate ion on the cured resins decreased in the order: propionaldehyde≈acrylaldehyde>butyraldehyde>crotonaldehyde>acetaldehyde>furfuial> formaldehyde. The optimum pH for the adsorption of the chromate ion was in the range 3.0 to 4.0. In the case of the cured diphenyl phosphonate-propionaldehyde resin, the amount of the adsorption of the chromate ion was 20.5 mg Cr/g resin. Under the same conditions, the amounts of the adsorption of molybdate and tungstate ions were 40.5 mg Mo/g resin and 80.0 mg W/g resin, respectively. The adsorbed chromate ion was recovered at approximately 80 wt% as chromium by elution with 1.0 mol/1 aqueous HCl solution. The adsorbed molybdate and tungstate ions were desorbed with 2.0 and 3.0 mol/l aqueous H2SO4 solutions, respectively. The recovery rate for Mo and W was 100 wt%. The mechanism of adsorption of the chromate ion on the cured resins having phosphinylden groups, (Remark: Graphics omitted.)P(O)H, has been discussed.

ChemInform Abstract: REACTION OF CHLOROPHOS ANALOGS WITH CARBOXYLIC ACID ANHYDRIDES

AbstractDie Phosphonate (I) bilden ohne Lösungsmittel in Gegenwart von wenig Schwefelsäure bei 30‐100°C mit Carbonsäureanhydriden (II) die 1‐Acyloxy‐Derivate (III).

Reaction of chlorophos analogs with carboxylic acid anhydrides

The corresponding acyl derivatives were obtained when dialkyl (1-hydroxy-1-methyl-2,2-dichioroethyl) phosphonates and dialkyl or diphenyl (1-hydroxy-1methyl-2,2,2-trichloroethyl)phosphonates are reacted with carboxylic acid anhydrides.