76 results about "Total synthesis" patented technology

The invention provides a chemical synthesis method of a TIMP2 protein N-terminal structural domain. An amino acid sequence of an N-terminal structural domain of TIMP2 protein is divided into four segments, the four segments are synthesized by a solid-phase polypeptide synthesis method, full-length linear polypeptide is obtained through natural chemical connection, sulfur removal and sulfydryl removal and acetamino methyl removal, finally impurities in a system are removed, the full-length linear polypeptide is dropwise added into a refolding reaction system, oxidation and refolding reactions are carried out, and the TIMP2 protein is obtained. A target product is obtained. The N-TIMP2 of the N-terminal structural domain of the TIMP2 retains the inhibitory activity of the TIMP2 on the MMP14, the N-TIMP2 obtained through chemical total synthesis can introduce non-natural amino acid to any site in the sequence or perform specific modification or mutation in the synthesis process, an effective tool is provided for researching the specific action mechanism of the N-TIMP2 and the MMP14, and a foundation is further laid for research and development of the MMP14 inhibitor.

The invention belongs to the technical field of coal mine machinery lubrication and hydraulic transmission, and discloses an environment-friendly total-synthesis concentrated solution for a hydraulic support and a preparation method of the concentrated solution. The biological sensing microcapsule corrosion inhibitor is characterized by comprising 0.5%-3.0% of a biological sensing microcapsule, 8.0%-15.0% of a main corrosion inhibitor, 2.0%-6.0% of an auxiliary corrosion inhibitor, 4.0%-10.0% of a water-soluble lubricant, 0.05%-0.2% of an anti-foaming agent, 1.0%-3.0% of a pH buffering agent and deionized water. Wherein the biological sensing microcapsule has a core-shell-shell structure, is integrated with electroactive microorganisms, an electron mediator carrier and a corrosion inhibition precursor release layer, and can trigger targeted release of benzotriazole derivatives when the pH value of a local corrosion microarea is less than or equal to 5.5. The corrosion inhibitor has excellent corrosion protection performance and environment-friendly characteristics, effectively overcomes the problem of inactivation of microorganisms under severe hydraulic working conditions through a microcapsule encapsulation strategy, realizes accurate matching of corrosion signal in-situ sensing and corrosion inhibition response, remarkably improves the anti-rust performance under high-shear and wide-temperature-range working conditions, and has wide application prospects. And meanwhile, the requirements of environmental protection and sealing material compatibility are met.

The application discloses a full synthesis method of clethodim, and the method is characterized by reasonable selection / design of a process route, simplified process flow, reduced separation and purification operation, effectively reduced production cost and improved production efficiency, further improved yield of a key intermediate through research and screening of process conditions of the key step, reduced generation of impurities, and improved product quality and yield of the target product.

The invention discloses a preparation method of 4-chloro-2-fluoro-3-methoxyphenylboronic acid and a preparation method of the 4-chloro-2-fluoro-3-methoxyphenylboronic acid. The specific implementation process comprises the following steps: by taking 1-bromo-4-chloro-2-fluoro-3-methoxybenzene as a raw material, carrying out Grignard reaction on magnesium chips and an initiator in an organic solvent to synthesize 4-chloro-2-fluoro-3-methoxyphenyl magnesium bromide; and the 4-chloro-2-fluoro-3-methoxyphenyl magnesium bromide and boric acid ester are synthesized into the 4-chloro-2-fluoro-3-methoxyphenylboronic acid, and then the 4-chloro-2-fluoro-3-methoxyphenyl magnesium bromide and boric acid ester are synthesized into the 4-chloro-2-fluoro-3-methoxyphenylboronic acid. The novel synthesis method of 4-chloro-2-fluoro-3-methoxyphenylboronic acid is designed, the total synthesis yield of the method ranges from 88% to 95%, compared with an existing synthesis route, the problems that a traditional route relates to an ultralow temperature condition and strong alkali, is low in safety and high in cost are solved, and the method has the advantages of being simple, environmentally friendly, safe, efficient and the like and is suitable for industrial production. Meanwhile, the method has a relatively good industrialization prospect.

The invention discloses a method for preparing an ester compound and a macrolide compound, and belongs to the technical field of organic chemistry, the preparation method of the ester compound is as follows: in an organic solvent, an alpha-carbonyl alkenyl ester compound reacts with alcohol or phenol under the catalytic condition of alkali to obtain the ester compound; the preparation method of the macrolide compound comprises the following step: in an organic solvent, carrying out intramolecular hydroxyl reaction on an alpha-carbonyl alkenyl ester compound under the catalysis condition of alkali or acid, thereby obtaining the macrolide compound. The method is wide in substrate range, high in practicability and high in yield, racemization of a carboxylic acid alpha-chiral center can be inhibited in intermolecular esterification reaction and macrocyclic lactonization reaction, and the method can be applied to total synthesis of a Brevicidine natural product containing a 13-membered cyclic ester peptide core structure; the method disclosed by the invention has the advantages of mild reaction conditions, simplicity, easiness in operation, wide substrate adaptability, no racemization of the product and the like.

The present application relates to the field of drug synthesis, in particular to a novel intermediate, a method for preparing the same and application thereof. The structural formula of the novel intermediate provided by the present application is as expressed by formula I:where R is a secondary amine protection group. Based on the possible biogenic pathway of morphine derivatives, the present application realizes the efficient synthesis of morphine derivatives through the strategy of biomimetic synthesis, taking the asymmetric transfer hydrogenation reaction and the intramolecular oxidative dearomatization Heck reaction in the process of preparing the intermediate as the key reactions of total synthesis. Using the novel intermediate provided by the present application to synthesize morphine derivatives has the characteristics of significantly reducing the synthesis steps, improving the yield, reducing the discharge of three wastes and reducing the production cost.

This invention relates to "an efficient and safe method for synthesizing perfluoropentanone," belonging to the field of organic chemical synthesis. The method for synthesizing perfluoropentanone is characterized by the following steps: under the action of hexafluoropropylene CF2=CF-CF3, fluorophosgene CF2O, and trifluorobromomethane CF3Br, perfluoropentanone (C5F) is generated in the gas phase. 10 O. The raw materials of this invention are inexpensive and readily available; the product separation and purification are simple; it is easy to industrialize; and it produces less industrial waste.

The invention relates to a preparation method and application of 6-methyl-3, 5-dioxocapryloyl coenzyme A. According to the preparation method, 2-methylbutyric acid serves as a starting raw material, the 6-methyl-3, 5-dioxocapryloyl coenzyme A is chemically synthesized through the steps of activation, condensation, coenzyme A coupling and the like, and the structure and purity of the 6-methyl-3, 5-dioxocapryloyl coenzyme A are identified through the technologies of LC-MS / MS, 1HNMR and the like. The nine-carbon coenzyme A is successfully prepared and identified through a chemical synthesis method for the first time, the core problem that an intermediate is unstable and cannot be obtained in vitro is solved, and a stable substrate is provided for in-vitro acyl transfer; the QS-21 in-vitro acyl transfer reaction is realized for the first time, an in-vitro catalytic system of a chemical synthesis intermediate and an insect cell expression enzyme is established, and a foundation is laid for development of a QS-21 total synthesis process.

Provided are a method for the total synthesis of compound I, SMTP-7 (also known as JX10, BIIB131 or TMS-007) and derivatives, intermediate compounds involved in the total synthesis method of compound I, as well as uses of the intermediate compounds and the synthesis methods thereof.

This invention discloses a ginsenoside Rg5 derivative with the molecular formula: C 42 H 74 O 12 The molecular weight is 770.5180. Furthermore, this invention also discloses the synthesis method and application of this derivative. The synthesis method of this invention is simple and safe, and the synthesized ginsenoside Rg5 derivative exhibits strong stability and superior therapeutic effect on non-alcoholic steatohepatitis (NAH). This invention is the first to combine the prepared ginsenoside Rg5 derivative with the PDE4 inhibitor (R)-(-)-Rolipram, showing significantly better efficacy than either drug alone. When the molar ratio of the two drugs is 1:1, the drug exhibits even better therapeutic effect on NHA, showing promising application prospects.

The invention discloses a method for synthesizing a camptothecin chiral precursor with high enantioselectivity, and belongs to the field of organic synthesis. In the invention, the preparation of a chiral precursor amide compound of camptothecin comprises the following steps: synthesizing corresponding aryl (E)-2-ethylbutyl-2-olefine acid ester, mixing the aryl (E)-2-ethylbutyl-2-olefine acid ester with a phase transfer catalyst derived from cinchona alkaloid in an organic solvent, sequentially adding acid, potassium permanganate and a small amount of potassium fluoride solution for reaction, and after the reaction is finished, performing suction filtration to obtain the chiral precursor amide compound of camptothecin. Carrying out amine ester exchange with diethylamine; and evaporating the solvent, and quickly purifying by using a silica gel column to obtain the camptothecin precursor chiral amide compound with high enantioselectivity. The invention aims at providing a new thought and a new method for total synthesis of camptothecin based on a camptothecin chiral precursor reported in literatures, and broadens a synthesis route for synthesizing camptothecin.

The invention discloses an alpha-amino amide derivative and a synthesis method thereof. According to the synthesis method of the alpha-amino amide derivative, halogenated difluoroacetate, aromatic aldehyde or alkyl aldehyde and alkylamine or aromatic amine are used as raw materials, under the catalysis of metal copper salt, Bronsted acid is used as an additive, an organic reagent is used as a solvent, and the alpha-amino substituted amide derivative is obtained through a one-step reaction. The raw materials are cheap, easy to obtain, safe and non-toxic, the reaction conditions of the synthesis method are mild, the operation is simple and safe, and the synthesized alpha-amino substituted amide derivative can be widely applied to the fields of organic synthesis and drug research and development.

The present application belongs to the technical field of microbiology, and particularly relates to a polypeptide for inhibiting the activity of influenza virus neuraminidase 2. The polypeptide of polyporus umbellatus is extracted, the polyporus umbellatus polypeptide is fractionated by using a Bio-Rad high-pressure chromatography system, and the polypeptide sequence with a higher inhibition rate and higher abundance is picked for full synthesis under the guidance of influenza virus neuraminidase 2 inhibition activity screening, so as to obtain a polypeptide monomer as shown in the sequence table SEQ ID NO. 1. The results of the examples show that the polypeptide monomer can effectively inhibit the activity of influenza virus neuraminidase 2, and further provides a new direction for an anti-influenza virus active substance.

The invention provides wide-temperature-range alkyl naphthalene base oil as well as a synthesis method and application thereof, and the synthesis method of the wide-temperature-range alkyl naphthalene base oil comprises the following steps: mixing naphthalene and alpha-olefin, and performing Friedel-Crafts alkylation reaction under the action of a catalyst of a modified Y-type molecular sieve to obtain long-chain alkyl naphthalene. According to the present invention, the viscosity index of the prepared alkyl naphthalene is similar to the viscosity index of the commercial alkyl naphthalene of the same type, the temperature interval of the open flash point and the pour point is wide, the method has characteristics of strong adaptability and strong practicality, the use range of the alkyl naphthalene as the base oil raw material is efficiently improved, and the quality of the total synthesis lubricating oil finished product oil is improved.

The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of hancolide A. The preparation method provided by the application comprises the following steps: Michael addition reaction of a compound of formula II with a cinnamic acid derivative or a phenylpropynic acid derivative to obtain a compound of formula III or a compound of formula III-1; FC acylation reaction of the compound of formula III or the compound of formula III-1 to obtain a compound of formula IV or a compound of formula V; oxidation of the compound of formula IV to obtain the compound of formula V; methylation of the compound of formula V to obtain a compound of formula VI; and deprotection of the compound of formula VI to obtain the compound of formula I. The application is a low-cost, full-synthesis route of hancolide A suitable for industrial production.

The application provides a fuzi glycoside analogue shown in formula I with a cardiotonic effect, and provides a new choice for clinical drugs with cardiotonic and anti-heart failure effects; meanwhile, the application also provides a synthesis method of the fuzi glycoside analogue, and enriches the total synthesis route of the fuzi glycoside analogue.

This invention discloses novel cyclic tripeptide compounds from cicada molts, their preparation methods, and applications, relating to the field of pharmaceutical development technology. This invention extracts and isolates two racemic cyclic tripeptide compounds from cicada molts using methanol and ethanol-water, respectively, and then synthesizes them totally, with the following structural formulas: [structural formulas omitted]; named Pericicapeptide A (compound 1) and Pericicapeptide B (compound 2). This is the first time that novel cyclic tripeptide compounds have been isolated and identified from cicada molts, and this invention is also the first to disclose a method for extracting, isolating, and totally synthesizing the new compounds Pericicapeptide A and Pericicapeptide B from cicada molts. Structural identification confirms that these small molecule compounds are novel racemic cyclic tripeptide compounds. Experimental verification shows that they can prevent and treat neuroinflammation and depression by inhibiting the level of pro-inflammatory cytokines induced by LPS in BV2 cells.

The invention relates to a novel total synthesis method of a natural product Atriicepheol A and an analogue thereof, and belongs to the technical field of organic chemistry. Economical and easily available 2, 4-dihydroxy methyl benzoate is used as a raw material, a compound 1 is synthesized through a functional group protection strategy, and the compound 1 is subjected to methylation and hydrolysis reaction to obtain a compound 3; introducing an aldehyde group into sesamol to obtain a compound 4; the compound 3 and the compound 4 are subjected to a condensation reaction to obtain a compound 5, and the compound 5 is subjected to MOM group removal under the acidic condition to obtain the natural product Atriicepheol A (6). And then the compound 6 is respectively subjected to methylation and acetylation to synthesize analogues 7 and 8 of the compound Atriicepheol A. The synthesis method has the advantages of economical and easily available raw materials, simple operation and high yield, is suitable for large-scale production, and can provide a large amount of raw materials for biological activity research.

The invention belongs to the field of total synthesis of natural products, and relates to a method for asymmetrically synthesizing a natural product (+)-Tronanocarpine. According to the method, a known compound S1 and commercially available 4-cyclohexanone carboxylic acid are taken as synthesis starting points, and manganese-mediated oxidative cyclization is utilized to construct a key indolo-azabicyclo [3.3. 1] bridged ring system. The preparation method comprises the following steps: introducing an exocyclic aldehyde group through a recarburization reaction, and further carrying out a nucleophilic addition reaction and deprotection spontaneous cyclization to obtain seven-membered ring lactam to obtain a basic skeleton precursor of (+)-Tronanocarpine. Finally, the asymmetric total synthesis of the (+)-Tronanocarpine is realized through a series of functional group conversion such as lithium triethylborohydride selective reduction amide, Dess-Martin oxidation reaction and the like. The method lays a material foundation for subsequent research on pharmacological values of the natural products and development of anticancer innovative drugs for reversing multidrug resistance.

This document discloses a method for generating intermediates in the total synthesis of (+)-daunoglobin or its derivatives, and the total synthesis of (+)-daunoglobin or its derivatives. This document also discloses methods for forming compounds of formula XIV and XV, wherein compounds of formula XIV and XV are as defined in the specification.

The invention belongs to the technical field of biological medicines, and particularly relates to a drug-loaded nano-micelle as well as a preparation method and application thereof. According to the invention, bromoalkanes with different chain lengths are introduced to a leonurine phenolic hydroxyl group by adopting a total synthesis method to prepare a leonurine derivative, and the drug-loaded nano-micelle is prepared by applying triptolide (TP) and the leonurine derivative. The embodiment of the invention verifies that the drug-loaded nano-micelle can reduce in-vivo and in-vitro toxicity caused by triptolide and improve the treatment effect on a mouse arthritis model induced by type II collagen. The novel triptolide compatible medicine prepared by the invention is small in toxic and side effects and has a good curative effect on rheumatoid arthritis.

The invention relates to a liquid-phase synthesis method and application of 5 '-triphosphoric acid modified oligonucleotide. The liquid-phase synthesis method comprises the following steps: synthesis of 5'-terminal phosphoric acid modified oligonucleotide, ammonolysis, salting-out, activation of 5 '-terminal phosphoric acid, connection of pyrophosphoric acid and ethanol precipitation. According to the invention, a liquid phase method is creatively designed to synthesize the oligonucleotide modified by triphosphoric acid, the dependence on a solid phase carrier can be avoided, the synthesis process is safe, the synthesis efficiency is high, the application scene of the synthesis is obviously expanded, and safe, stable and cheap synthesis of the oligonucleotide modified by 5 '-triphosphoric acid is realized.

Disclosed herein are enantioselective synthetic methods of preparing known cyclic imine (CI) toxins and analogs thereof as small molecule inhibitors of NMD3 with selectivity and potent anti-cancer activity.

The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of tricyclic prostaglandin D2 metabolite methyl ester. The synthesis route of the tricyclic prostaglandin D2 metabolite methyl ester of the application adopts a catalyst which is easy to obtain, and raw materials and catalysts are cheap, low in cost, green and environmentally friendly. The synthesis route of the tricyclic prostaglandin D2 metabolite methyl ester of the application is completed in a short time at a low temperature, the reaction condition is very mild, operation is simple and safe, and is conducive to industrial production. The application realizes asymmetric total synthesis research of the tricyclic prostaglandin D2 metabolite methyl ester from commercially available starting materials through 10 steps, and realizes large-scale preparation of hundreds of milligrams.

The present disclosure provides the first asymmetric total synthesis and target identification of the curcusone natural products. The novel convergent synthesis is built upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl3-promoted global hydrolysis / adol condensation cascade to rapidly construct the critical cycloheptadienone core. By performing chemoproteomics with the alkyne probe 37, we identified the previously “undruggable” oncogenic protein BRAT1 as a key cellular target of 1d. Furthermore, 1d inhibits BRAT1 in cancer cells, thereby reducing cancer cell migration, increasing susceptibility to DNA damage, and inducing chemosensitization to the approved drug etoposide. Compound 1d is the first known small-molecule inhibitor for BRAT1, a master regulator of the DDR and DNA repair. Composition matters and methods of uses are within the scope of this disclosure.

The application provides a reaction molecule prediction method, a training method, a device and an electronic device. The method comprises: performing feature extraction on a product molecule to obtain a feature of the product molecule; based on the feature of the product molecule, using a reverse reaction prediction model to predict a conversion path between the product molecule and a plurality of reaction molecules, to obtain a target path; and synthesizing a sub-path and completing a sub-path according to the target path to obtain a plurality of reaction molecules corresponding to the product molecule. The method provided by the application can not only reduce the prediction complexity of the reaction molecules and improve the generalization performance of the reaction molecule prediction, but also improve the prediction performance of the reaction molecules. The plurality of reaction molecules corresponding to the sub-path; the basic graph comprises a plurality of atoms or edges for connecting the atoms.

This invention relates to the field of enzyme engineering technology, and in particular to a total synthetic ketone reductase and its applications. The amino acid sequence of the total synthetic ketone reductase is shown in SEQ ID NO:2 or SEQ ID NO:3. This total synthetic ketone reductase can be used to prepare (S)-3-hydroxytetrahydrofuran. Specifically, recombinant engineered bacteria are cultured, lysed, and added to a reaction system containing substrate compound II, NAD+, and isopropanol. The reaction yields compound I. The specific route is as follows: the recombinant engineered bacteria are *E. coli* BL21(DE3) as the host and pET-30a(+) as the vector, expressing the above-mentioned total synthetic ketone reductase. The ketone reductase of this invention can stably express heterologous functionality, and it exhibits highly efficient catalytic activity in the preparation of the chiral compound (S)-3-hydroxytetrahydrofuran, demonstrating significant potential for industrial application.

Disclosed are a method for biological total synthesis of paclitaxel key precursor substance baccatin III, a biological material and use thereof. The bioenzyme composition used in the method comprises a taxane 9α-hydroxylase (T9αH) and a taxane C4-C20 oxetanase (TOT). According to the disclosure, a core component of a baccatin III biosynthetic pathway is identified, a baccatin III artificial synthesis route is constructed, thereby paving the way for efficiently developing a green low-carbon production pathway of taxane products (such as paclitaxel) through synthetic biology.

The application discloses a kind of Δ 8 - Synthesis method and Δ 8 - Application of THC. Wherein, the synthesis method comprises the following steps: taking cannabidiol as raw material, adding organic solvent, converting under ultraviolet light to generate Δ 8 - THC. According to the technical scheme of the application, cannabidiol CBD is converted into Δ 8 - THC under the catalysis of ultraviolet light, so that Δ 8 - THC appears as main product, and the method for converting CBD also ingeniously avoids complex and high-cost total synthesis route.