Aminated Cyclopropylmethylphosphonates as Potent Prostate Cancer Inhibitors

Inspired by the anti-pancreatic promising results of our novel aminated cyclopropylmethylphosphonate compounds, an in vitro anti-prostate cancer activity exploration of these compounds was carried out on human prostate cancer cell line PC-3, and showed potent inhibiting activity at low micromolar concentrations (with an IC50 of approximately 45 μM).

Aminated (Cyclopropylmethyl)Phosphonates: Synthesis and Anti-Pancreatic Cancer Activity

Buoyed by the extensive research on the wide-range biological activities of aminophosphonates, a novel class of aminated (cyclopropylmethyl)phosphor-nates compounds was synthesized from diethyl ((1-(3-chloropropyl)cyclopropyl)methyl)phosphonate and various amines in the presence of Hunig’s base. Upon biological activity screening these compounds demonstrated encouraging anti-pancreatic cancer properties at low micromolar concentrations.

Enantioselective synthesis of chiral phosphonylated 2,3-dihydrofurans by copper catalyzed asymmetric formal [3+2] cycloaddition of propargylic esters with β-keto phosphonates

Copper catalyzed asymmetric formal [3＋2] cycloaddition of propargylic esters toβ‐keto phospho‐nates for the synthesis of chiral phosphonylated 2,3‐dihydrofurans was developed. By using a bulky and structurally rigid tridentate ketimine P,N,N ligand, a series of optically active phosphonylated 2,3‐dihydrofurans were prepared in high yield and up to 92%ee.

Design, synthesis and in vitro evaluation of L-amino acid esters prodrugs of acyclic nucleoside phosphonates as anti-HBV agent

A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.

Synthesis of α-[2-(2, 4-Dichlorophenoxy) Propionyloxy] Alkyl Phosphonates

The synthesis of thirteen new compounds α - [2 - (2, 4 -dichlorophenoxy) propionyloxy] alkyl phosphonates was described. The structures of these compounds were characterized by IR, 1H-NMR and MS.

REACTIONS OF 1-ACETOXY ALLYLIC PHOSPHONATES UNDER PALLADIUM(0) CATALYSIS

l-Acetoxy allylic phosphonates rearrange regioselectively to γ-acetoxy α,β-unsaturated phosphonates under the catalysis of Pd(0). l-Acetoxy allylic phosphonates act as the precursors of phosphonatedπ-allylic cations in palladium(0) catalyzed reactions[1]. The reactions of l-acetoxy allylic phosphonates under palladium(0) catalysis with nucleophiles have been reported. 1-4 These reactions are highly regio- and stereoselective. We wish to report here the palladium(0) catalyzed reaction of l-acetoxy allylic phosphonates in the absence of a nucleophile.

AN EFFICIENT SYNTHESIS OF α-(BENZOTHIAZOL-2-YLOXY)PHOSPHONATES DERIVATIVES

Fifteen title compounds 3a-0 were synthesized by condensation of 2chloro-benzothiazole with a-hydroxyphosphonates in good yields us- ing potassium iodide/tetrabutyl ammonium bromide as catalyst.All new com- pounds have been identified by ~1H-NMR,IR and elemental analysis.

SYNTHESES OF HINDERED ALKYL PHOSPHONATES AND PHOSPHONIC & PHOSPHINIC ACIDS

A series of di-n-hexyl alkyl phosphonates with bulky substituent on phosphorus was synthesized by PTC P-alkylation using crown ether.Upon saponification of the resulting di-n-hexyl alkylphosphonates in the presence of crown ether or quaternary ammonium halide, corresponding mono-hexyl esters of alkyl phosphonic acids were prepared.Ultrasonic wave, as we found, can catalyze the reaction between dialkyl phosphite & metallic sodium and hydrolysis of dihexyl alkyl phosphonates.A series of di-t-alkyl phosphinic acids were synthesized by the reaction of Grignard reagent with PCl_3 followed by oxidation with 30% H_2O_2.It was found that the reaction between dibutyl phosphite and Grignard reagent of t-alkyl chloride is a new synthetic method for the preparation of mono-esters of highly hindered alkyl phosphonic acids.

Synthesis and Structural Chemistry of Two Novel Transition Metal Organic Phosphonates

Two novel transition metal phosphonate compounds, [Co（H2BDPP）（phen）]n 1 （BDPP = p-O3PCH2（C6H4）CH2PO3, phen = 1,10-phenanthroline） and [Pb3（BCP）2]n 2 （BCP = OOC（C6H4）CH2PO3）, have been synthesized and structurally determined by X-ray single-crystal diffraction. Compound 1 crystallizes in the monoclinic system, space group C2/c with a = 21.169（4）, b = 12.001（2）, c = 7.6211（15）A, β = 98.03（3）°, V= 1917.2（6）A^3, C20H18N2O6P2Co, Mr = 505.22, Z = 8, De= 1.737 g/cm^3, p = 1.107 mm^-1, F（000） = 1020, the final R= 0.0450 and wR = 0.1306 for 2072 observed reflections （I 〉 2σ（I）. Compound 2 crystallizes in the monoclinic system, space group C2/c with a = 4.7167（9）, b = 18.753（2）, c = 22.781（3）A, β = 91.07（3）°, V= 2014.7（14）A^, C8H6O5PPb1.5, Mr = 523.88, Z = 8, Dc = 3.454 g/cm^3, p = 25.222 mm^-1, F（000） = 1856, the final R = 0.0441 and wR = 0.1906 for 2259 observed reflections （I 〉 2σ（I）. In compound 1, the 1D chain running along the c axis is bridged by four ligands （trans- HO3PCH2C6H4CH2PO3H） in four different directions to extend the structure into a three- dimensional network. In compound 2, the Pb（II） displays 4- and 5-coordination modes. There is a one-dimensional P-O-Pb band along the a axis formed by PO3 groups and Pb（II） cations. These bands are joined by μ2-O of -COO to yield two-dimensional inorganic P-O-Pb layers which are pillared by the OOCC6HaCH2PO3 ligands to form a three-dimensional network. Moreover, compound 2 displays a strong emission band attributed to the ligand-centered （LC） transition.

Synthesis, Characterization and X-ray Crystal Structure of O,O~ˊ-Dipropyl α-（2,4-Dichlorolphenoxyacylamido）-α-（4-methoxyphenyl） Methylphosphonates

A new crystal of O,Oˊ-dipropyl-α-（2,4-dichlorolphenoxyacylamido）-α-（4-methoxyphenyl） methylphosphonates has been prepared at room temperature and characterized by elemental analysis and IR,MS,1H NMR spectra,13C NMR spectra and X-ray single-crystal determination.The complex crystallizes in triclinic,space group P1 with a = 7.858（2）,b = 12.621（4）,c = 12.621（4）,α = 96.17（3）,β = 90.960（3）,γ = 90.960（3）°,V = 1243.9（7）3,Dc = 1.346 Mg/m3,Z = 2,μ = 0.362 mm-1and F（000） = 528.

Iodine-catalyzed Synthesis of α-Amino Phosphonates

Iodine was found to be an efficient catalyst for the one pot synthesis of α-amino phosphonate from aldehydes, anilines and diethyl phosphite. The influences of the iodine loading, reaction solvent, the structure of aldehyde and aniline on the reaction were studied.

Structure Reactivity Studies on the Extraction of Rare Earths by Di(2-ethylhexyl)chloroalkyl Phosphonates

The extractive separation properties and the extractive regularity of the lanthanide elements by five di(2-ethylhexyl)alkyl phosphonates with various alkyl structure:di(2-ethylhexyl)chloromethyl phosphonate CH_2ClP(O) (OC_8H_(17)-i)_2(1),di(2-ethylhexyl)β-chloroethyl phosphonate ClCH_2CH_2P(O) (OC_8H_(17)-i)_2 (2),di(2-ethylhexyl)α-chloroethyl phosphonate CH_3CHClP(O)(OC_8H_(17)-i)_2 (3),and corresponding di(2-ethylhexyl)methyl phosphonate CH_3P(O)(OC_8H_(17)-i)_2 (4),di(2-ethylhexyl)ethyl phosphonate C_2H_5P(O) (OC_8H_(17)-i)_2 (5),in nitrate system have been studied.The coordination compounds were prepared. The structure of these extractants and their coordination compounds were further explored by IR and ^(31)P NMR spectra.

Design,synthesis and in vitro evaluation of mono(2,2,2-trifluoroethyl)esters,mono L-amino acid ester prodrugs of acyclic nucleoside phosphonates as anti-HBV agents

A series of novel mono（2,2,2-trifluoroethyl） esters,mono L-amino acid ester prodrugs of acyclic nucleoside phosphonates was synthesized and their in vitro anti-HBVactivity was evaluated in HepG 2 2.2.15 cells.Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil and alamifovir（MCC-478） with EC_（50） and CC_（50） values of 0.01μmol/L and 8000μmol/L respectively.

Synthesis of N-(alkoxycarbonyl or alkoxycarbonyl-methyl-alkoxyphosphonyl)-α-amino-O,O-diphenyl phosphonates and their bioactivities

<正> With phosphoric formic acid (PFA) and its analog,phosphonoacetic acid (PAA),as the lead compounds,α-amino phosphonates were introduced into PFA and PAA.The derivatives oi N-( alkoxycarbonyl-aikoxyphosphonyl)-α-arnino phosphonates (Ⅰ) and N-(alkoxycarbonyl-methyt-alkoxyphosphonyl)-α-amino phosphonates (Ⅱ) with the N-terminal of amino phosphonates bonding to phosphorus atom of PFA and PAA were synthesized via the reaction of the corresponding phosphonyl chloride with a-amino phosphonates in the presence of a base.The 31P NMK spectra of Ⅰ and Ⅱwere determined.It is found that the coupling constants 3Jpp with R3 being alkyl group were lower than those with R3 being (substituted) phenyl,and this result was discussed.The preliminary bioassay showed that some of the compounds Ⅰ and Ⅱhave better activities against tobacco mosaic virus (TMV).The inhibitory was higher than that of DHT (2,4-dioxyhexahydro-1,3,5-triazine).In addition,some of the compounds showed the activity against cancer cells.

Enhanced removal of phosphonates from aqueous solution using PMS/UV/hydrated zirconium oxide process

Traditional treatment processes cannot completely remove phosphonates in circulating cooling water by one-step method. Herein, we designed peroxymonosulfate/UV irradiation/hydrated zirconium oxide(PMS/UV/HZO) coupling process to enhance the phosphonates removal. In particular, nitrilotrismethylenephosphonic acid(NTMP) removal efficiency by PMS/UV/HZO process was much higher than that of PMS/UV process, UV/HZO process and other processes in comparison experiments. Specifically,almost 97.2% NTMP in water was degraded, and the total phosphorous(TP) reduced from 9.3 mg/L to 0.26 mg/L at pH 7 within 180 min. TP removal efficiency still reached above 90% after 5 cycles adsorptiondesorption of HZO. Moreover, Cl^(-), NO_(3)-and SO_(4)^(2-)ions all had negligible effect on NTMP removal. During the process, NTMP was first destroyed to form phosphates and other intermediates by the reactive oxygen species(ROS), then phosphates were in situ immobilized via HZO adsorption. Sulfate radical(SO_(4)^(·-))has been confirmed to be the major ROS in the reaction system by quenching experiment and electron paramagnetic resonance(EPR) characterization. And the excellent selective adsorption capacity of HZO for phosphate produced was attributed to the strong inner-sphere coordination between H_(2)PO_(4)-/HPO_(4)^(2-)and Zr-OH on the surface of HZO. These results suggest that PMS/UV/HZO process is a promising technique for enhanced phosphonates decontamination.

Lewis Acid Enables Ketone Phosphorylation:Synthesis of Alkenyl Phosphonates

Main observation and conclusion An efficient Lewis acid enabled ketones phosphonylation to synthesize vinylphosphonates has been developed.This method relays on ketone hydrophosphonylation/α-hydroxy phosphonates unimolecular elimination(E1)dehydration cascade reaction sequence.

Amberlyst-15 catalyzed synthesis of alkyl/aryl/heterocyclic phosphonates

A novel and efficient procedure for the synthesis of alkyl phosphonates through one pot condensation of alkyl halide and trialkyl /aryl phosphite in the presence of Amberlyst-15 as catalyst under solvent free conditions was applied.It demonstrated several advantages such as good yields of products,simple operation,convenient separation and inexpensive catalyst.

Facile synthesis of ( β -chlorodifluoroethyl)phosphonates via chlorination reaction of difluoroalkyl diazo derivatives with HCl

An efficient chlorination reaction of in situ generated(β-diazo-α,α-difluoroethyl)phosphonates has been achieved with hydrochloric acid as a chlorine source under mild and operationally convenient conditions.The reaction does not need any catalyst and tolerates a wide scope of substrates,which affords the(β-chlorodifluoroethyl)phosphonate products in good to excellent yields.This reaction represents the first example of the halogenation of difluoroalkyl diazo compounds,and also provides an easy way for the synthesis of difluoromethylenephosphonate-containing compounds.

Rh（Ⅰ）-Catalyzed Arylation of α-Diazo Phosphonates with Aryl Boronic Acids： Synthesis of Diarylmethylphosphonates

An efficient synthetic method for diarylmethylphosphonates is presented.A series of phosphonate derivatives with diverse functional groups can be accessed via a rhodium catalyzed cross-coupling reaction between a-diazo phosphonates and aryl boronic acids.Migratory insertion of rhodium carbene intermediates is postulated to be the critical step in this transformation.

Synthesis of Quaternary α-Hydroxy Phosphonates via Direct Hydroxylation of Phosphonate Compounds

It was found for the first time that Cs_(2)CO_(3) serves as highly efficient catalyst for the direct hydroxylation reactions of phosphonates under mild conditions.This reaction provides an efficient approach to quaternaryα-hydroxy phosphonates,which possess intriguing biological activities and are widely used in many areas.