67 results about "Aminophosphonate" patented technology

This application discloses phosphoramidate and phosphonoamidate prodrugs of alcohol-based therapeutic agents, such as nucleosides, nucleotides, acyclonucleosides, C- nucleosides, and C-nucleotides, and use of these prodrugs for treatment of diseases or disorders, including infectious diseases and cancers. This application also discloses a general method for enhancing bioavailability and/or liver-targeting property of alcohol drugs through converting the alcohol drugs to phosphoramidate or phosphonoamidate prodrugs, and methods of preparation of these prodrugs.

This invention relates to a method for preparing roinyl diterpene modified alpha-aminophosphate, and its anti-tumor application. The method comprises: reacting roinyl amine diterpenoid with substituted benzaldehyde and phosphite at a mol ratio of 1 :( 1-1.05) :( 1-1.1) by solvent synthesis, one-pot synthesis or solvent-free synthesis. The inroduction of roinyl diterpene into aminophosphate can largely improve the liposolubility and bioactivity of the compound. R1 structure comes from natural product rosin, thus has low toxicity.

The invention discloses a method for synthesizing alpha-aminophosphonate through water phase cleaning. Aromatic aldehyde, amine and phosphite ester are used as raw materials, non-ionic surface active agents are used as catalysts, water replaces organic solvents to be used as reaction media, the heating and stirring reaction is carried out at ordinary pressure, and the synthesis of the target compound is realized. Compared with the prior art, the method has the advantages that (1) Tween-20 and Tween-60 non-ionic surface active agents are adopted, raw material resources are wide, the preparation is convenient, and safety and reliability are realized; (2) the catalytic activity is high, the use consumption is little, the stability on the water is realized, the catalysts are not inactivated, and the cyclic use can be realized; and (3) a water phase reaction method is adopted, the environment pollution caused by the organic solvent use is avoided, in addition, the post treatment is convenient, the reaction is safe and stable, the industrial amplification is easy, and energy saving and emission reduction effects are obvious. The method belongs to an efficient and environment-friendly method for synthesizing alpha-aminophosphonate compounds, and the large-scale industrial production is favorably realized.

The invention discloses an alpha-amino phosphonate compound with a 2-amino-1, 3, 4-thiadiazole structure and a preparation method and application of alpha-amino phosphonate compound. The alpha-amino phosphonate compound has the sterilizing effect of alpha-amino phosphonate compounds and has a pesticide effect by introducing the 2-amino-1, 3, 4-thiadiazole group, and the alpha-amino phosphonate compound is wide in application range and good in sterilizing and pesticide effect by combining the alpha-amino phosphonate compound with the 2-amino-1, 3, 4-thiadiazole group. The preparation method is few in step, simple to operate, high in yield and productivity, capable of saving a large amount of time and cost in actual production and good in economic benefit. The 2-amino-1, 3, 4-thiadiazole has an inhibition effect on the growth and proliferation of alternaria solani and on the growth of mythimna separata and can be used as the pesticide intermediate to apply to the preparation of different agricultural fungicide.

The invention discloses a series of rhein aminophosphonate derivatives, and a synthetic method and applications thereof. The synthetic method of the rhein aminophosphonate derivatives comprises: taking rhein and an alpha-aminophosphonate as raw materials, dissolving in a polar solvent, in the presence of a catalyst HOBT and a condensing agent EDAC, reacting completely; and adding trichloromethane into the reaction liquid, washing with water, collecting the organic layer, applying to silica gel for column chromatography, eluting with a mixed solvent of ethyl acetate and petroleum ether with a volume ratio of 1:4-100 to obtain the corresponding derivative. The rhein aminophosphonate derivatives have the structural general formula (I) as shown in the description, wherein R is p-bromophenyl, o-bromophenyl, m-bromophenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, m-methoxyphenyl, o-methoxyphenyl, phenyl, naphthyl, p-methoxyphenyl, m-methylphenyl, p-methylphenyl, m-fluorophenyl or anthryl.

The invention discloses an efficient and novel method for preparing aminophosphonate through catalytic synthesis of hafnium tetrachloride. With hafnium tetrachloride as a catalytic reagent, aryl/alkyl aldehyde, aryl/alkyl amine and phosphorous acid diester/triester as raw materials, and ethyl alcohol as a solvent, a one-pot reaction is performed for 0.5-2.0 h at 60 DEG C to generate corresponding aminophosphonate, wherein the dosage of the hafnium tetrachloride catalytic reagent is 2 mol% that of aldehyde, and the concentration of aldehyde in an ethanol solution and the concentration of amine in the ethanol solution are both 1.0 mol/L. Hafnium tetrachloride used in the method is high in catalytic activity, small in dosage, capable of achieving the optimum catalytic effect at the dosage of 2 mol%, universally applicable to various aryl aldehyde/amine substrates and alkyl aldehyde/amine substrates and high in product yield. According to the method, reaction conditions are mild, heating is performed just at 60 DEG C, the ethyl alcohol solvent does not need drying, a reaction system does not need gas protection, the reaction speed is high, aftertreatment and purification are easy, and it is only needed to concentrate the reaction system and directly perform conventional silica-gel column chromatography.

The invention provides a method for synthesizing chiral aminophosphonates through organocatalytic Friedel-Crafts reactions. An organic catalyst used in the method is chiral phosphoric acid. Corresponding chiral aminophosphonates with quaternary carbon centers can be prepared by catalyzing asymmetric Friedel-Crafts reactions of a series of imidophosphonates with indole, and enantiomeric excess is up to 98%. The method provided by the invention is simple, practical and feasible; the catalyst is commercially available; and reaction conditions are mild. In addition, since the chiral aminophosphonates is synthesized through the asymmetric Friedel-Crafts reactions, high enantioselectivity and good yield are realized, and the reactions have the advantages of atomic economy, environmental friendliness and the like.

The invention discloses alizarin aminophosphonate derivatives and their synthesis method and use. The synthesis method comprises that alizarin and 2-bromopropionic acid as raw materials are dissolved in a polar solvent, the solution undergoes a reaction in the presence of potassium hydroxide as an acid binding agent to produce 2-(1-hydroxy-9, 10-dioxo-9,10-dihydroanthracene-2-yloxy)propionic acid, the 2-(1-hydroxy-9,10-dioxo-9,10-dihydroanthracene-2-yloxy)propionic acid and alpha-aminophosphonate as raw materials are dissolved in a polar solvent, the solution undergoes a full reaction in the presence of 1-hydroxybenzotriazole as a catalyst and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride as a condensing agent, trichloromethane is added into the reaction produce solution, a water washing process is carried out, and an organic layer is collected and then is subjected to chromatography purification by a silicagel column. The alizarin aminophosphonate derivatives have a general structural formula (I).

Provided is a method for synthesizing chiral gamma-aminophosphonates. Starting from azadiene and phosphite, reacting is conducted under the action of an inorganic base and an organic catalyst to obtain the chiral gamma-aminophosphonate containing various substituents. The method has simple and practical operation, high yield and high enantioselectivity.

The present invention discloses a class of chiral alpha-amino phosphonate ester compounds having anti-virus activity and containing benzothiazole heterocycle, preparation and applications thereof, wherein the structure of the compound is represented by the following general formula (I). According to the present invention, thiourea or thiourea quinidine is adopted as a chiral catalyst, a 4A molecular sieve is adopted as a cocatalyst, and dichloromethane is adopted as solvent to rapidly synthesize the high yield and high optical activity chiral alpha-amino phosphonate ester compound containing benzothiazole heterocycle at a room temperature; and especially treatment, protection and activity passivation of the compound R-4h on cucumber mosaic virus are superior to the commercial agent ningnanmycin, treatment, protection and activity passivation of the compound R-4q on tobacco mosaic virus are superior to the commercial agent ningnanmycin, and the compounds R-4h and R-4q provide good inhibition effects on tobacco mosaic virus (TMV), cucumber mosaic virus (CMV), Southern rice black-streaked dwarf virus (SRBSDV) and the like, have good universality, and can be used for anti-plant virus chiral pesticide preparation. The formula (1) is defined in the specification.

The invention provides chirality oliopeptide phosphonate thiourea derivatives and application and a preparation method thereof. A series of chirality oliopeptide phosphonate thiourea derivatives of novel structures are designed and synthesized. Each derivative comprises an amino acid skeleton, a thiourea-based functional group and an amino phosphonate component, and the molecular structure is provided with multiple chirality centers. Meanwhile, the compounds have a good inhibiting effect on plant viruses, and are suitable for preparing plant virus resistant agents and particularly suitable for new pesticide creation and research for tobacco mosaic viruses (TMV). The preparation method is good in reliability, good symmetry selectivity and high yield are achieved, and the material basis is provided for follow-up research. The material source is simple, and the material is easy to obtain, low in cost and good in use effect.

The present invention provides β-hydroxy-γ-aminophosphonates, β-amino-γ-aminophosphonates, and analogs thereof that inhibit carnitine acyltransferases. The invention also provides compositions comprising these β-hydroxy-γ-aminophosphonates, β-amino-γ-aminophosphonates, and analogs, and methods of the use of such compounds and compositions in the treatment, amelioration or prevention of pathological conditions, diseases or disorders that are linked with fatty acid metabolism, such as non-insulin dependent diabetes or obesity. The invention also provides processes for the preparation of such compounds and compositions.

The invention discloses a biphenyl alpha-aminophosphonate compound as well as a preparation method and an application thereof. The structural formula of the compound is shown in the specification. The compound has very good antiviral activity on plant viruses and can be applied to preparation of anti-plant-virus pesticides, especially anti-CMV (cucumber mosaic virus) pesticides. The preparation method of the biphenyl alpha-aminophosphonate compound has the advantages that raw materials are easy to obtain, reaction conditions are mild, a reaction process is simple to operate, a reagent is cheap and the like.

The present invention relates to novel phosphonoamidate prodrugs of acyclic nucleoside phosphonates with a 3-fluoro-2-(phosphonomethoxy)propyl side chain. The invention also relates to the use of these novel phosphonate-modified nucleosides to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, particularly infections with viruses such asthe hepatitis B virus, the human immunodeficiency virus, the human cytomegalovirus and the varicella zoster virus.

The invention discloses a method for preparing optically-active alpha-amino phosphonate derivatives by chiral spiro phosphate catalysis. Chiral spiro phosphate serves as a catalyst, imine and dialkyl phosphate are stirred in an organic solvent at room temperature, and high-purity optically-active alpha-amino phosphonate derivatives are prepared by a simple post-treatment purification process. The method is mild in reaction condition, simple in process and convenient in operation. The catalyst is high in stability and can be reused. The prepared optically-active alpha-amino phosphonate derivatives are high in potential biological activity and can be used as organic synthesis intermediates.

Belonging to ocean chemical engineering technologies, the invention specifically relates to a furyl alpha-aminophosphonate chitosan derivative and its preparation method. The general formula of the derivative is shown as formula I, wherein, R is an alkyl group and n=4-4000. The preparation method comprises: taking chitosan as a matrix, which is mixed with dialkyl phosphite and furfural, and conducting reaction at a temperature of 0-120DEG C and under microwave power of 10-1000W for 1-60min, immersing the reactant with a solvent, then conducting pumping filtration, washing the filter cake with the solvent, and carrying out drying so as to obtain the furyl alpha-amidophosphonate chitosan derivative. Specifically, the chitosan, the dialkyl phosphite and the furfural are in a molar ratio of 1:1-3:1-3. In the invention, furyl alpha-aminophosphonate is introduced into a chitosan structure, and the two generate synergistic effects, thus significantly improving the antibacterial activity of chitosan.