115 results about "Total synthesis" patented technology

The invention belongs to the technical field of organic synthesis and medicinal chemistry, and discloses a total synthesis method of rhododendron heteroterpenin Rhododaurines A-C. The total synthesis method comprises the following steps: carrying out allyl stereoselective addition on a compound 3 and a compound 5 in a toluene solvent under the conditions of catalysis of n-butyllithium and low temperature of-78 DEG C, and constructing a chiral center to obtain a compound 6; removing a methoxy methyl (MOM) protecting group from the compound 6 under an acidic condition, cyclizing, and reacting to generate rhododaurine C (7); the rhododaurine C (7) is subjected to intramolecular [4 + 2] cycloaddition and oxidation reaction in the illumination and oxygen atmosphere of 300-385 nm, and rhododaurine B (8) and an epoxy epimer epinedodaurine B (9) are obtained; and carrying out protonation and rearrangement on the epidodaurine B (9) by virtue of acid catalysis cyclic ether, so as to generate the rhododaurine A (10). The method can overcome the defects that the content of rhododendron miscellaneous terpenoids Rhododaurines A-C in nature is extremely low, and large-scale extraction is difficult.

A preparation method, intermediates, and use of a cyclic peptide toxin α-Amanitin and / or Amaninamide are provided, belonging to the technical field of organic synthesis. A total synthesis method of the cyclic peptide toxin compounds α-Amanitin and Amaninamide is provided, where raw materials and reagents used are easily purchased through commercial channels, the intermediates are stable, and the preparation method shows mild reaction conditions, simple operation process, desirable operability of separation and purification, and high yield. The preparation method also shows important reference and practical value, can achieve gram-scale preparation of the α-Amanitin and Amaninamide, and has excellent industrial prospects. Therefore, the preparation method is of significant application value in the field of cyclic peptide toxin synthesis.

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 invention discloses a continuous flow synthesis method of chloracetyl-L-glutamine and glycyl-glutamine, and belongs to the technical field of organic synthesis. According to the invention, molecular-level efficient mixing and heat conduction of materials are realized, so that the reaction materials are fully mixed, the reaction is more sufficient, the conversion rate is further improved, and the process operation is safe and controllable. The micro-channel reactor has the advantages that equipment is relatively small, the reaction is continuous flow, the feed flux is large, the occupied area of the equipment is reduced, and the productivity is improved. Through a micro-channel continuous flow method, ammonia water or ammonia gas is directly adopted without adding ammonium bicarbonate, the problem that the ammonia water cannot be used mechanically is solved, the recycled ammonia water treated after reaction can be directly used mechanically, three wastes are thoroughly solved, and the production process is green and environment-friendly. The glycyl-L-glutamine is totally synthesized through micro-channel continuous flow, the product purity HPLC (High Performance Liquid Chromatography) of the glycyl-L-glutamine reaches 99.5% or above, and the single impurity content is less than 0.1%.

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 invention discloses a compound for treating methamphetamine addiction and cognitive impairment, its preparation method and application. The new compound NBU513-1 for treating methamphetamine addiction and cognitive impairment induced by the present invention can significantly improve the addictive behavior of mice for methamphetamine, has a therapeutic effect on the cognitive dysfunction caused by methamphetamine, and can be used to prepare a medicine for treating methamphetamine addiction and cognitive impairment induced by methamphetamine. The present invention provides a total synthesis route of compound NBU513-1. Compared with the preparation method of similar compounds in the prior art, the method of the present invention does not need to react with sodium azide, does not produce powerful explosives and highly toxic substances, has high stability and low reaction risk; the method has mild reaction conditions, simple scheme, safe and reliable production and can prepare target products with higher yields, and is suitable for industrial production.

The invention provides a novel method for preparing an intermediate compound of aromatic sesquiterpenes Commiphoranes C-D. The method comprises the following steps: substituting the ortho-position of a compound 1 with iodine through n-butyllithium and diiodoethane to obtain a compound 2; removing methoxyl by using boron tribromide to obtain a compound 3; performing nucleophilic substitution on 3-allyl bromide and potassium carbonate to synthesize a compound 4; carrying out Grignard reaction to obtain a compound 5; oxidizing into a compound 6 through a Dess-Martin oxidizing agent; finally, (CH3Si) 3SiH and triethyl boron are subjected to intramolecular free radical series cyclization, so that synthesis of an aromatic sesquiterpene Commiphoranes C-D intermediate compound is successfully completed, sufficient preparation is made for follow-up total synthesis of the natural product, key intramolecular free radical series cyclization has the capacity of efficiently constructing a polycyclic system, and the synthesis process is simple and convenient. According to the preparation method, the defects of expensive reagents, long 14-step linear synthesis route, low yield and the like in the existing synthesis route are overcome; the popularization potential is high.

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.

The invention belongs to the technical field of anti-cancer drugs, and particularly discloses a 1, 2-diphenylethyl propiolamide compound as well as a preparation method and application thereof. The 1, 2-diphenylethyl propyne amide compound disclosed by the invention is novel in structure and relatively good in activity, has relatively good anti-tumor activity as an inhibitor, and has relatively good inhibition activity on various tumor cells such as human non-small cell lung cancer cells, human pancreatic cancer cells and human breast cancer cells; the compound can be applied to preparation of anti-tumor drugs. The invention provides a total synthesis method and a derivative preparation method of a 1, 2-diphenylethyl propyne amide compound. The preparation method has the advantages of cheap and easily available raw materials, short reaction period, simple operation and the like.

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 discloses a total synthesis method and application of furanose ring pyrrole spiroketal alkaloid, and belongs to the technical field of chemical synthesis and biological medicine. According to the method, D-glucose is used as a raw material and reacts with dibenzylamine, 1-dibenzylamino-1-deoxy-D fructose is prepared through an Amadori rearrangement reaction, 1-amino-1-deoxy-D fructose is prepared through direct hydrogenation debenzylation, or 2-hydroxyl of 1-dibenzylamino-1-deoxy-D fructose is protected by adding methyl and then debenzylation protection is carried out, and 1-amino-1-deoxy-D fructose is obtained. The preparation method comprises the following steps: preparing 1-amino-1-deoxy-2-methoxyl-D-fructose; and respectively carrying out Maillard condensation reaction on the two obtained amino sugars and dihydropyrone, and then completing spiro reaction under an acidic condition to obtain acorine B and pinosine C. The acorine B and pinosine C synthesized by the invention can obviously reduce the weight of an aged mouse, reduce the fat index, reduce lipid droplets in the liver and fat in thymus, reduce the number of aged cells and improve the proportion of T cells in immune cells, and have the potentials of reducing fat and resisting immune aging.

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 an asymmetric total synthesis method of a natural product (-)-Lucidutone. The total synthesis of the natural product takes known compounds S1 and S2 as synthesis starting points, and a basic skeleton of (-)-Lucidutone is constructed through key reactions such as key Lewis acid catalyzed intramolecular Diels-Alder, hydroboration oxidation, Suzuki coupling, acid catalyzed deprotection / Prins reaction / cyclic etherification series connection and the like. The asymmetric total synthesis method of the (-)-Lucidumone is successfully invented at a relatively high total yield by carrying out a series of functional group conversion such as Fleming-Tamao oxidation, Grieco elimination and Wacker oxidation on the (-)-Lucidumone and then carrying out a series of functional group conversion such as the Fleming-Tamao oxidation, the Grieco elimination and the Wacker oxidation. The synthesis method is relatively simple to operate, can be widely popularized and used, and lays a solid foundation # imgabs0 # for deeper pharmacological and physiological activity research of (-)-Lucidutone

The invention discloses a cefalonium hapten, an antigen, an antibody as well as a preparation method and application thereof, and relates to the cefalonium hapten, the antigen, the antibody as well as the preparation method thereof and the application in detecting cefalonium residues. The cefalonium hapten and the artificial antigen as shown in the formula (I) are prepared by using a total synthesis method, and a specific antibody for detecting cefalonium is further prepared. The cross reaction rate of the antibody prepared from the hapten / antigen to common structural analogues is lower than 0.01%, the accuracy is high, the interference of other structural analogue drugs can be effectively eliminated, and a basic raw material is provided for subsequent further development of an immune rapid detection technology and a product aiming at cefalonium. # imgabs0 # is represented by formula (I).

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.

The present invention discloses a functionalized isoquinolone and quinolone compounds and an efficient transition-metal-free approach for the synthesis of the same. The invention provides a highly functionalized isoquinolones from the reaction of dimethyl-2-((phenylamino)methylene) malonate with aryne precursors under mild. The reaction proceeds through insertion of aryne into the C−C σ-bond, which offers a novel and practical entry to access a wide range of isoquinolones with enhanced yields. The substrate scope is broad as the process can stands a variety of functional groups and the application of the developed process has been demonstrated in the total synthesis of antimalarial agent SJ000101247. Also, the highly functionalized quinolones are also useful in the synthesis of floxacins based compounds and derivatives e.g. ciprofloxacin, norfloxacin, G003967, etc.