33 results about "Phosphoramidate" patented technology

The invention provides a modified phosphoramidate intemucleotide linkage, referred to herein as a fiuorosulfonyl phosphoramidate (fsP) internucleotide linkage, wherein the fsP intemucleotide linkage has the structure of formula (I) modified oligonucleotides comprising at least one tsP intemucleotide linkage, and methods of using the modified oligonucleotides comprising at least one fsP internucleotide linkage.

The invention provides a method for efficiently preparing various substituted chiral phosphoramides, which comprises the following steps: in the presence of an organic solvent, alkali, a chiral ligand and a catalyst, reacting a nucleoside compound or alcohol with racemic amino phosphoryl dichloride or alkoxy phosphoryl dichloride to generate chiral phosphoryl chloride; and reacting the chiral phosphoryl chloride with a nucleophilic reagent to obtain the chiral phosphamide. The synthesis method provided by the invention is simple to operate, high in yield and good in diastereoselectivity or enantioselectivity, and the obtained target compound has the characteristics of good functional group compatibility and wide substrate universality. The obtained product is diversified in structure and good in controllability, and has good application potential in the field of medicine synthesis.

The invention discloses a process for removing calcium ions and magnesium ions from nitrate-containing quaternary system brine, and relates to the technical field of brine treatment. The method comprises the following steps: filling a single column with modified composite resin, enabling the nitrate-containing quaternary system brine to pass through the column, and collecting outlet liquid to obtain the calcium ion and magnesium ion removed nitrate-containing quaternary system brine. Wherein the modified composite resin is prepared by the following steps: pretreating phosphoramidate chelate resin with dopamine, compounding the pretreated phosphoramidate chelate resin with nano-crystalline cellulose, a synergist and functionalized carbon quantum dots, cross-linking with a silane coupling agent KH560, and finally soaking with acid and alkali and purifying. The nano cellulose, the synergist, the functionalized carbon quantum dots and the like are introduced, and a specific process method is matched, so that the calcium and magnesium adsorption capacity, the permeation wear impact force resistance, the pollution resistance and the lithium loss resistance of the treatment process are effectively improved. Therefore, the treatment process disclosed by the invention has a wider application prospect.

The invention relates to a high-adhesion anti-stripping primer special for a metal substrate and a preparation method thereof, and belongs to the technical field of paints.The primer comprises silane modified phosphoramidate chelating resin, graphite oxide-Schiff base zirconium-siloxane hybrid filler, a hyperbranched polyamide-siloxane bonding accelerant, an isocyanate curing agent, functional auxiliaries and the like. The silane modified phosphoramidate chelating resin is prepared by carrying out a reaction on bisphenol F epoxy resin and diethylenetriamine, and carrying out a reaction on p-toluenesulfonic acid, diethyl phosphite, KH540 and hydroquinone. The graphite oxide-Schiff base zirconium-siloxane hybrid filler is prepared from the following components: GO-SB, ZrO2-siloxane core-shell particles, zirconium n-propoxide and the like. The hyperbranched polyamide-siloxane bonding accelerator is prepared by the following steps: reacting ethylenediamine with methyl acrylate, then reacting with ethylenediamine, and then modifying with KH540 and perfluoroalkyl phosphate. The problems that a traditional primer is weak in interface bonding force, easy to peel off and insufficient in corrosion resistance are solved.

Nucleotides with alpha-imino phosphate groups and bridging sulfurs, and methods of synthesizing and using the same, are provided herein. In some examples, a nucleotide may include a sugar, a nucleobase coupled to the sugar, an alpha-imino phosphate group, and a bridging sulfur coupling the alpha-imino phosphate group to the sugar.

This invention provides a method and equipment for producing lithium carbonate for batteries. The method includes the following steps: S1, crushing and grinding lepidolite ore into fine particles with a particle size of less than 75 μm; S2, placing the ground lepidolite particles into a flotation device to obtain lepidolite concentrate using a flotation process. The lithium carbonate production method provided by this invention incorporates phosphate and carboxylic acid groups into the collector. The phosphate groups in the aminophosphate molecule can form stable chemical bonds or complexes with lithium ions on the surface of lepidolite, enhancing the binding force between the collector and lepidolite, increasing the collection ability of lithium minerals, and improving selectivity. The interaction with the surface of lepidolite is specific, while the interaction with the surface of gangue minerals is weaker, thus better enhancing its selectivity and improving the quality of the lepidolite concentrate, laying the foundation for the subsequent production of higher quality lithium carbonate.

The application provides a phosphoramidate morpholino antisense oligonucleotide for antiviral, which comprises a base sequence shown as SEQ ID NO. 1, the antisense oligonucleotide is a phosphoramidate morpholino antisense oligonucleotide, the structural formula of the phosphoramidate morpholino nucleotide monomer in the antisense oligonucleotide is shown in the following formula, Base is a base; R is N, N-dimethylamine or piperazine. The antisense oligonucleotide can be combined with a specific region in the fifth segment of viral RNA of an influenza virus, block the transcription of the viral RNA through steric hindrance, play an antiviral role, and use a PMO structure which is good in nuclease stability, high in antisense efficiency and good in water solubility, and at the same time, by introducing a piperazine group which is positively charged under physiological conditions, the PMO compound can enter the cell across the membrane, and the biological activity of the compound can be effectively enhanced.

Embodiments for the synthesis of sensitive oligonucleotides as well as insensitive oligonucleotides are provided. Sulfur-based groups are used for the protection of exo-amino groups of nucleobases, phosphate groups and 2′-OH groups, and as cleavable linker for linking oligonucleotides to a support. Oligonucleotide syntheses are achieved under typical conditions using phosphoramidite chemistry with important modifications. To prevent replacing sulfur-based protecting groups by acyl groups via cap-exchange, special capping agents are used. To retain hydrophobic tag to assist RP HPLC purification, special phosphoramidites are used in the last synthetic cycle. With the sulfur-based groups for protection and linking, oligonucleotide deprotection and cleavage are achieved via oxidation followed by beta-elimination under mild conditions. Therefore, besides for insensitive oligonucleotide synthesis, the embodiments of the invention are capable for the synthesis of oligonucleotide analogs containing sensitive functional groups that cannot survive the harsh conditions used in prior art oligonucleotide synthesis technologies.

Provided herein are monosaccharides, e.g., compounds of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for cell labeling for diagnostic and / or therapeutic applications. [Formula 1] TIFF2025541836000133.tif18170

The application discloses low immunogenic collagen and a preparation method and application thereof, and the preparation method comprises the following steps: (1) performing enzymolysis on animal skin; (2) performing salt precipitation treatment on the enzymolysis glue liquid; (3) adding organic amino phosphoric acid or a salt thereof to replace and purify the crude collagen protein prepared through the salt precipitation treatment after redissolving the crude collagen protein, and then performing salt precipitation treatment to obtain purified collagen protein; and (4) redissolving, dialyzing and freeze-drying the purified collagen protein to obtain low immunogenic collagen. Through replacement and removal of DNA impurity molecules on collagen molecular chains by using phosphate in organic amino phosphoric acid or the salt thereof, the amino in the organic amino phosphoric acid or the salt thereof can promote the combination of the phosphate and the collagen under the action of intermolecular hydrogen bonds between the amino and residual carboxyl on the collagen, and the amino and the phosphate play a synergistic effect, so that the removal effect of the DNA impurity in the collagen can be further improved, and the immunogenicity of the collagen is reduced.

The invention provides a synthesis method of aryl phosphate, and solves the problems of harsh reaction conditions, existence of potential safety hazards, high requirements on equipment, tedious process, low yield, high cost and the like which are not beneficial to industrial production in the existing synthesis method. The preparation method comprises the following main preparation steps: S1, reacting chloro phosphate with different types of amines to obtain phosphoramidate; s2, the phosphoramidate and different kinds of benzyne precursors are subjected to an arylation reaction under the fluoride condition, and aryl phosphate is obtained.By means of the one-pot method, the experimental operation process can be simplified, generation of by-product impurities is avoided, the yield is greatly improved through condition screening, and the obvious effect is achieved.

The invention discloses a preparation method of amino phosphorylation synergistically modified nano calcium carbonate, which comprises the following steps: adding 10-20g of nano calcium carbonate into 200mL of absolute ethyl alcohol or deionized water, and treating for 30 minutes by an ultrasonic dispersion instrument to form a uniform dispersion liquid; dissolving 5-15g of a phosphorus source compound in deionized water; taking a nitrogen source compound accounting for 10-20% of the mass of the nano calcium carbonate, slowly adding the nitrogen source compound and the phosphorus source compound solution in the step S2 into the dispersion liquid in the step S1, and stirring while adding; placing the mixed solution in a magnetic stirrer for stirring reaction, and adjusting the pH value of the system to be neutral by using NaOH or HCl after the reaction is finished; washing the product with deionized water for multiple times until the pH value of the solution is close to neutral, and removing unreacted phosphorus source and nitrogen source compounds; and drying the washed product in a vacuum drying oven until the weight is constant, thereby obtaining the phosphoramidated synergistically modified nano calcium carbonate. The P-N modified nano calcium carbonate can be synergistically used with a phosphorus-nitrogen flame retardant, so that the addition amount of the phosphorus-nitrogen flame retardant is reduced, and the cost is reduced.

This invention relates to the field of polymer functional materials and water treatment technology, and discloses a preparation process of a bifunctional chelating resin of a metallo-oxime-aminophosphate group, comprising the following steps: S1. Swelling treatment: Styrene-divinylbenzene (St-DVB) copolymer white spheres are used as the matrix. Aminophosphate groups and metallo-oxime groups are simultaneously grafted onto the resin backbone to form a unique bidentate chelating structure. The aminophosphate groups are highly acid-resistant and can preferentially act on heavy metal complexes in acidic water environments, weakening the coordination bond between the complexing agent and copper ions. The metallo-oxime groups are rich in nitrogen and oxygen coordinating atoms, which can quickly capture dissociated copper ions. The two groups form a chemical synergistic effect, which is not a simple superposition of adsorption performance. X-ray photoelectron spectroscopy characterization proves that the nitrogen and oxygen atoms of both functional groups can participate in the coordination of copper ions to form a stable chelating ring, breaking the thermodynamic equilibrium of strongly complexed heavy metals and avoiding the problem of traditional resins being unable to break the complex.

The invention discloses synthesis of 3 '-amido-5-nucleotide phosphamide and application of the 3'-amido-5-nucleotide phosphamide in oligonucleotide. The phosphamide modified oligonucleotide comprises at least one of nucleotide structural units shown in a formula I, a formula II, a formula III or a formula IV,..., the formula I, the formula II, the formula III,..., the formula IV. Through specific limitation of a nucleotide phosphamide monomer structure, oligonucleotides are prepared by coupling according to a direction from 5 to 3. Compared with a traditional oligonucleotide molecule, the oligonucleotide molecule provided by the invention contains phosphamide modification and has more excellent effects on pharmaceutical parameters such as enzymatic degradation resistance, stability and the like, in addition, the phosphamide modification can improve the binding performance between the modified oligonucleotide molecule and environmental ions, and the stability of the oligonucleotide molecule is improved. A novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

Provided herein are monosaccharides, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for cell labeling for diagnostic and / or therapeutic applications.

Provided herein are oligonucleotides comprising a phosphoramidite internucleotide bond having the formula: (I) wherein R1 is isopropyl, isobutyl, sec-butyl, C1-6 haloalkyl, C2-6 hydroxyalkyl, C2-8 alkylene-N (RN) 2, C0-2 alkylene-C3-8 cycloalkyl, 4-10 membered heterocycloalkyl having 1-3 ring heteroatoms selected from O, N and S, or 5-10 membered heteroaryl having 1-3 ring heteroatoms selected from O, N and S, with the proviso that the heterocycloalkyl group or the heteroaryl group is attached to sulfur via a carbocyclic atom, and the cycloalkyl group, the heterocycloalkyl group or the heteroaryl group is substituted with 0, 1, 2 or 3 R2 groups; each R2 is independently halo, CN, N (RN) 2, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, oxo, CO2RN, or C (O) C1-3 alkyl; and each RN is independently H or a C1-3 alkyl group. Also provided are formulations comprising the oligonucleotides disclosed herein and methods of treating diseases and disorders using the oligonucleotides disclosed herein and formulations thereof.

The invention discloses a floxuridine phosphamide ester prodrug and application thereof in preparation of a medicine for treating liver cancer, and belongs to the technical field of medicine. The invention designs and synthesizes a series of 5-FdU phosphamide ester derivatives which are subjected to specific esterification modification at 3 '-site. Different aromatic acyl, fatty acyl or amino acid residues are introduced to the 3 '-site, so that the lipophilicity of molecules is further adjusted to enhance liver tissue distribution, and the enrichment and activation process of the medicine in the liver is optimized by utilizing the steric hindrance or metabolic lysis characteristic of the 3'-site. Experiments prove that the series of compounds show excellent anti-hepatoma cell proliferation activity and good pharmacokinetic characteristics, and a new choice is provided for clinical treatment of liver cancer.

The present invention relates to phosphoramidate nucleotide compound 1: The present invention provides a stereoselective method for producing TIFF2023538594000234.tif132170 or a pharmaceutically acceptable salt thereof.

This invention provides a flotation collector for high-sulfur complex lead-zinc polymetallic ores, its preparation method, and its application. The collector is N,N'-dibromophenyl dithioaminophosphate, prepared by reacting o-bromoaniline with phosphorus pentasulfide in toluene. This collector exhibits strong collecting ability, good selectivity, non-sticky flotation froth, low middlings recycling volume, and strong adaptability for lead sulfide minerals. It is convenient to use, requires a small dosage, and simplifies the flotation process, reducing flotation costs and environmental impact, thus achieving better flotation separation of high-sulfur lead-zinc ores. Furthermore, this collector can also recover various associated gold and silver minerals in high-sulfur complex lead-zinc polymetallic ores, demonstrating broad applicability and strong adaptability, especially for fine-grained associated gold and silver minerals with a particle size less than 37 μm, exhibiting strong collecting ability and good selectivity.

The invention discloses a preparation method of an aminophosphorylated nano calcium / phosphorus-nitrogen agent synergistic flame-retardant polypropylene material, which comprises the following steps: adding 10-20g of nano calcium carbonate into 200mL of absolute ethyl alcohol or deionized water, and treating for 30 minutes by using an ultrasonic dispersion instrument; the preparation method comprises the following steps: dissolving 5-15g of a phosphorus source compound in deionized water; slowly adding a phosphorus source compound and a nitrogen source compound into the nano calcium carbonate dispersion liquid; putting the mixed solution on a magnetic stirrer, and reacting for several hours; regulating the pH value of the reaction system to be neutral by using NaOH or HCl; after the reaction is finished, washing the nano calcium carbonate with deionized water for multiple times, carrying out vacuum drying at 80 DEG C after centrifugal washing, and crushing to obtain phosphorus-nitrogen flame-retardant nano calcium carbonate; the preparation method comprises the following steps: mixing phosphorus-nitrogen flame-retardant nano calcium carbonate with dried polypropylene, a phosphorus-nitrogen flame retardant and an antioxidant at a high speed, carrying out melt blending granulation by virtue of a double-screw extruder, and finally carrying out injection molding by virtue of an injection molding machine, so as to obtain the phosphoramidated nano calcium / phosphorus-nitrogen agent synergistic flame-retardant polypropylene material / phosphorus-nitrogen flame retardant compounded flame-retardant polypropylene composite material.

Nucleotides with alpha-imino phosphate groups and bridging sulfurs, and methods of synthesizing and using the same, are provided herein. In some examples, a nucleotide may include a sugar, a nucleobase coupled to the sugar, an alpha-imino phosphate group, and a bridging sulfur coupling the alpha-imino phosphate group to the sugar.

The invention provides a non-distillative process for manufacturing amphetamine and substituted amphetamines, comprising obtaining a highly pure phosphoramidate compound, converting the highly pure phosphoramidate compound to an amphetamine sulfate compound, concentrating the amphetamine sulfate compound in isopropanol, and then salting out the amphetamine compound directly to obtain an amphetamine salt, the amphetamine salt selected from amphetamine saccharate, amphetamine sulfate, amphetamine aspartate, alkyl-amphetamine saccharate, alkyl-amphetamine sulfate, alkyl-amphetamine aspartate, aryl-amphetamine saccharate, aryl-amphetamine sulfate, aryl-amphetamine aspartate, and mixtures thereof.

The present invention relates to phosphoramidate prodrugs (phosphoramidate derivatives of nucleosides), in particular phosphoramidate prodrugs for use in the treatment of cancer, the present invention relates to pharmaceutical formulations and formulation strategies for use in pharmaceutical formulations, e.g., NUC-3373 (5-fluoro-2 '-deoxyuridine-5'-O-[1-naphthyl (benzyloxy-L-alanyl)] phosphate) and NUC-7738 (3 '-deoxyadenosine-5'-O-[phenyl (benzyloxy-L-alanyl)] phosphate), for example, NUC-3373 (5-fluoro-2 '-deoxyuridine-5'-O-[1-naphthyl (benzyloxy-L-alanyl)] phosphate). In particular, the present invention relates to formulations comprising a polar aprotic solvent, such as dimethylacetamide (DMA).

New phosphoramidite Cy5 derivatives can be used in automated DNA synthesis, allowing the labeling of DNA sequences with a wider array of chromophores than are presently commercially available. In addition to varying dye hydrophobicity / hydrophilicity, the 5,5′-substituents (including hexyloxy, triethyleneglycol monomethyl ether, tert-butyl, and chloro groups) can modulate electron donating / withdrawing character while also tuning resulting absorption and emission properties. Modification of the Cy5 periphery enables the tuning of photophysical properties, such as absorption and emission maxima, fluorescence quantum yield, and fluorescence lifetime.

The application discloses a trifluoromethyl cyclohexyl benzyl ether substituted nitrogen-containing organic acid derivative, a preparation method and application thereof, and belongs to the technical field of organic compound synthesis and medicine. The synthesis method of the trifluoromethyl cyclohexyl benzyl ether substituted nitrogen-containing organic acid derivative is obtained through two-step reaction, that is, first, a light extension reaction is carried out on a benzyl alcohol compound and hydroxynaphthaldehyde (or hydroxybenzaldehyde), then a Schiff base is generated after the amino acid ester hydrochloride (or amino sulfonic acid, or amino phosphoric acid) is reacted with the benzyl alcohol compound, and sodium cyanoborohydride is used for reduction (or simple hydrolysis is carried out after reduction), so the trifluoromethyl cyclohexyl benzyl ether substituted nitrogen-containing organic acid derivative is obtained. The preparation method has the characteristics of simple steps, mild reaction conditions and fast reaction, and meets the requirements of green chemistry. The compound prepared according to the method can selectively adjust S1P1 receptors without exciting S1P3 receptors, and is expected to be developed into a new preparation for treating inflammatory and immune related diseases such as pulmonary fibrosis, ulcerative colitis and multiple sclerosis.

The present invention belongs to the field of pharmaceutical preparations, and relates to an oral preparation, which comprises (a) a compound of formula (1) or a pharmaceutically acceptable salt, isomer, solvate, hydrate or crystal thereof; and (b) an adsorbent. The invention also relates to a preparation method of the oral preparation and application of the oral preparation in medicines for preventing and / or treating hepatitis C. The oral preparation disclosed by the invention can be completely dissolved out, is well absorbed in vivo, has few impurities and is good in stability.

The invention discloses synthesis of phosphamide derived from 3-sulfydryl nucleotide and application of the phosphamide to oligonucleotide. The phosphamide modified oligonucleotide comprises nucleotide structural units shown as a formula I or a formula II,..., the formula I,..., the formula II. Through specific limitation of a nucleotide phosphamide monomer structure, the prepared oligonucleotide comprises a phosphamide structural unit derived from 3-mercaptonucleotide; compared with the traditional oligonucleotide molecule, the phosphamide modified oligonucleotide molecule of 3-mercapto nucleotide shows better enzymatic degradation resistance and pharmaceutical stability. In addition, the phosphamide modification of the 3-mercapto nucleotide can improve the binding performance between the modified oligonucleotide molecules and environmental ions, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention discloses synthesis of phosphoramide derived from 5-mercapto nucleotide and application of the phosphoramide to oligonucleotide. The phosphoramide modified oligonucleotide comprises nucleotide structural units shown as a formula I or a formula II,..., the formula I,..., the formula II. Through specific limitation of a nucleotide phosphamide monomer structure, the prepared oligonucleotide comprises a phosphamide structural unit derived from 5-mercaptonucleotide. Compared with the traditional oligonucleotide molecule, the phosphamide modified oligonucleotide molecule of 5-mercapto nucleotide shows better enzymatic degradation resistance and pharmaceutical stability. In addition, phosphoramide modification of 5-mercapto nucleotide can improve the binding performance between modified oligonucleotide molecules and environmental ions, and a novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

The invention discloses a preparation method of a gamma-phosphoramidate derivative, which comprises the following steps: in an organic solvent, taking oxime ester (I), olefin (II) and a phosphate ester substrate (III) as initial raw materials, adding a photosensitizer, and reacting for 6-8 hours under the conditions of room temperature and illumination to prepare the gamma-phosphoramidate derivative (IV). A visible light strategy is adopted, and efficient conversion of olefin with different electronic characteristics and diversified structures is achieved. The method has the advantages that raw materials are stable and easy to synthesize; reaction conditions are mild, and experimental operation is simple; the chemical selectivity and the functional group tolerance are good, and the method is a green chemical synthesis method with a relatively good application prospect.