101 results about "Intramolecular cyclization" patented technology

Disclosed herein are methods of synthesizing compounds of the formula (I) wherein the variables are defined herein. Also provided are compounds produced using these methods. In some aspects, the methods provided herein may be used to install aryl bioisosteres.

The invention provides an application of two polycyclic polyisopentenyl acyl phloroglucinol compounds (PPAP) with different skeleton types in preparation of drugs for relieving / treating neurodegenerative diseases. Belongs to the technical field of medicines. Hypheronone A provided by the invention is a 1, 9-split-ring polycyclic polyisopentenyl phloroglucinol compound, and hypheronone L is a polycyclic polyisopentenyl phloroglucinol compound which is formed by carrying out intramolecular [4 + 2] cyclization on a monocyclic polyisopentenyl phloroglucinol compound and has a complex ring system. The compound hypherone A and the compound hypherone L both have the activity of enhancing the current of a voltage-gated T-type calcium channel, can be used for preparing medicines for treating neurodegenerative diseases, particularly can be used for preparing medicines for relieving and / or treating diseases such as spinal cerebellar ataxia, Alzheimer's disease and intellectual syndrome, and have clinical application value.

The present invention provides a method for preparing a trabectedin intermediate, specifically involving the generation of free radicals through electron transfer of a reaction substrate at the anode, and then the free radicals initiate an intramolecular cyclization reaction to prepare trabectedin intermediate A; in the method provided by the present invention, a series of reactions are carried out in the same system, without generating secondary pollution, and the reaction has high selectivity, short reaction steps, and significantly improved reaction yield.

The invention discloses a preparation method of an arfamarana key intermediate, which comprises the following steps: carrying out nucleophilic addition reaction on a compound I and 1-[3-chloro-5-(trifluoromethyl) phenyl]-2, 2, 2-trifluoroethanone under the action of an organic solvent A and alkali to obtain a compound II; dissolving the compound II in an organic solvent B, adding concentrated sulfuric acid, carrying out intramolecular dehydration and cyanogen hydrolysis, and after the reaction is finished, cooling to room temperature for crystal growing to obtain a compound III; dissolving the compound III in an organic solvent C, carrying out intramolecular cyclization and ester hydrolysis reaction on the compound III and hydroxylamine hydrochloride under the action of a certain amount of sodium hydroxide aqueous solution, and after the reaction is finished, collecting a water phase and adjusting the pH value of the water phase, so as to obtain the key intermediate of arfampanaga. The reaction in each step has a high conversion rate, the purity of the prepared arfamarin intermediate is high, and powerful support and guarantee are provided for preparation of high-purity arfamarin.

The invention discloses a method for co-catalyzing intramolecular cyclization of cis-epoxide by diarylboronic acid and tetrabutylammonium halide, and belongs to the technical field of organic synthesis. According to the method, diarylboronic acid and tetrabutyl ammonium halide are used as catalysts, and the bicyclol is synthesized through intramolecular ring closing reaction of cis-4-hydroxymethyl-1, 2-cyclopentene oxide in an organic solvent; according to the method, a cis-substrate is activated by diarylboronic acid, tetrabutylammonium halide is used as an instantaneous nucleophilic reagent to enable epoxy to be subjected to ring opening, oxygen in the substrate is subjected to intramolecular nucleophilic attack, and then halide ions are removed, so that an intramolecular ring closing product is obtained, and the reaction shows good functional group tolerance. The method has the characteristics of low catalyst dosage (one thousandth), simplicity and convenience in operation, high yield, environment friendliness and mild reaction conditions, and has potential practical application value.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a cyclobenzaprine intermediate 5H-dibenzo [a, d] cycloheptatriene-5-ketone. The preparation method comprises the following steps: preparing a magnesium Grignard reagent by taking 2-(2-chlorine or bromostyrene) benzonitrile as an initial raw material, and performing intramolecular cyclization and acidification to obtain a target compound I; the whole process is moderate in reaction temperature and mild in condition, use of expensive catalysts and special production equipment is avoided, and the production cost can be effectively reduced; meanwhile, the use of carbon tetrachloride and bromine with higher toxicity is avoided, the operation is safe, and the method is more suitable for industrial application.

The invention discloses a method for rapidly and efficiently preparing a series of novel ester group facaplysin derivatives by combining EDCI and HOBT to react with carboxyl facaplysin and directly carrying out ester exchange reaction on an active ester intermediate and alcohol without separation. The invention also discloses application of the derivatives in resisting methicillin-resistant staphylococcus aureus and escherichia coli. The preparation method comprises the following steps that EDCI and HOBT are combined to activate carboxyl facaplysin for reaction, an activated ester intermediate is generated, the activated ester intermediate and alcohol are directly subjected to esterification reaction without separation, and a series of ester-based facaplysin derivatives are obtained. According to the preparation method, ester-based Fascaplysin derivatives with different structures can be rapidly and efficiently constructed, and compared with a traditional method that ester-based carboline derivatives are firstly synthesized and then high-temperature intramolecular cyclization is performed, the time and the raw material cost are greatly saved, the synthesis efficiency is improved, the reaction process is observable and controllable, and the yield is stable. And the synthesized ester group facaplysin derivative has excellent antibacterial activity on methicillin-resistant staphylococcus aureus and escherichia coli.

The invention discloses a method for preparing an olaparib key intermediate compound as shown in a formula (1). The method comprises the following steps: (a) reacting a compound as shown in a formula (2) with a compound as shown in a formula (3) to generate a compound as shown in a formula (4); (b) carrying out intramolecular cyclization on the compound as shown in the formula (4) under the catalysis of acid to generate a compound as shown in a formula (5); (c) hydrolyzing the compound as shown in the formula (5) in an alkali solution, and acidifying to obtain a compound as shown in a formula (1); wherein in the compounds as shown in the formula (3), the formula (4) and the formula (5), R is formyl, acetyl, propionyl, butyryl, benzoyl, methoxycarbonyl, ethoxycarbonyl, t-butyloxycarbonyl, methylsulfonyl, benzenesulfonyl or p-toluenesulfonyl. The invention also discloses a compound shown in a formula (4) or a formula (5). The method is high in yield, mild in reaction condition, easy to purify and suitable for industrial large-scale production. # imgabs0 #

The invention relates to the technical field of cyclic polypeptides, in particular to a cyclic pentapeptide containing an Fmoc protecting group and a preparation method of the cyclic pentapeptide. The preparation method comprises the following steps: carrying out coupling reaction on dipeptide containing Fmoc-Cbz-lysine and tripeptide containing OBn-OtBu-glutamic acid to form straight-chain pentapeptide containing Fmoc, Cbz, OBn and OtBu; removing Cbz and OBn to form a straight-chain pentapeptide containing Fmoc and OtBu; carrying out intramolecular cyclization reaction to form cyclic pentapeptide containing Fmoc and OtBu; and removing OtBu to form the cyclic pentapeptide containing the Fmoc protecting group. The preparation method is high in cyclization yield, can adapt to various amino acid sequences, can synthesize the cyclic polypeptide containing the side chain protecting group, does not need a solid-phase carrier in the cyclization step, and can remarkably reduce the production cost.

The invention belongs to the technical field of fluorescent probes, and particularly relates to a single-molecule fluorescent probe based on a phenothiazine structure as well as a preparation method and application of the single-molecule fluorescent probe. The preparation method comprises the following steps: firstly introducing an alkyl chain to a nitrogen atom of a raw material to obtain the phenothiazine structure-based single-molecule fluorescent probe, then carrying out regioselective formylation on the raw material to obtain the phenothiazine structure-based single-molecule fluorescent probe, then treating the raw material by adopting aluminum trichloride to realize O-demethylation, and finally carrying out intramolecular cyclization reaction on the raw material and 1H-benzimidazole-2-acetonitrile to obtain the phenothiazine structure-based single-molecule fluorescent probe. The single-molecule fluorescent probe based on the phenothiazine structure prepared by the invention is compatible with orthogonal chemical reaction activity and maintains controllable electron transfer, so that different chemical events are converted into specific optical signals, and selective and mechanism specific fluorescent response to phosgene, copper ions and hypochlorite is realized.

The invention belongs to the technical field of resource recovery of scrapped chemical defense hazardous articles, and particularly relates to a resource recovery disposal method for scrapped Sieve explosion type tear bombs. Specifically, the invention provides a green process for directionally converting CS in a scrapped projectile body into a high-added-value medical intermediate 2-(2-chlorphenyl) benzimidazole. According to the process, pulverization pretreatment of a main charge grain is achieved through swelling treatment, wet crushing and drying, and CS is efficiently recycled through multi-step dissolution and extraction; cS and o-phenylenediamine are taken as raw materials, six-step continuous reaction of nucleophilic addition, acid-base neutralization, nucleophilic substitution, proton migration / elimination, intramolecular cyclization and oxidative aromatization is carried out, and the CS and o-phenylenediamine are directionally converted into 2-(2-chlorphenyl) benzimidazole. According to the disposal method, high-risk waste is converted into medical intermediates, waste resource utilization is achieved, pollution and safety risks caused by a traditional incineration / blasting method are avoided, and the problem of disposal of current decommissioning tear bombs is solved.

The invention discloses a synthesis method of a cyclic oligomer carbazole phosphate hole transport material. According to the material, carbazole phosphoric acid units are directionally connected into a cyclic oligomeric structure through intramolecular cyclization design, cyclic oligomer carbazole phosphoric acid with different hydrolysis degrees is obtained by adjusting the concentration of trimethylbromosilane in hydrolysis reaction, and the charge transfer capacity and the interface passivation effect of the material are remarkably improved. Compared with the traditional self-assembled monomolecular layer (SAM) type carbazole phosphoric acid micromolecule (such as PACz), the Cyclic-PACz has better long-term operation stability and large-area coating compatibility.

The present invention provides industrially suitable processes for preparing intermediates in the production of substituted polycyclic pyridone derivatives having a cap-dependent endonuclease inhibitory activity. In the process as shown below, wherein each symbol is as defined in the specification, an optically active substituted tricyclic pyridone derivative of the formula (VII) is obtained in high yield and high enantioselectivity by subjecting a compound of the formula (III) or (VI) to intramolecular cyclization with controlling stereochemistry to obtain a compound of the formula (IV) having a removable functional group on an asymmetric carbon, and then removing the functional group thereof;

This invention discloses a method for synthesizing a tenapano hydrochloride intermediate. The synthesis method includes the following steps: (1) condensing the compound 3-bromophenylacetaldehyde and the compound N-methyl-(2,4-dichlorophenyl)methylamine under dehydration conditions to obtain an enamine intermediate; (2) subjecting the enamine intermediate to an intramolecular cyclization reaction in the presence of an acid catalyst to obtain the tenapano hydrochloride intermediate 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline. The synthetic route provided by this invention requires only two steps to construct the key framework, and has the advantages of short reaction steps, high overall yield, and no need to use highly toxic liquid bromine. This process has high atom economy, reduces the emission of waste gas, wastewater, and solid waste, and is suitable for large-scale industrial production under mild conditions.

The invention relates to a method for preparing 2-aryl-3-difluoromethyl benzothiophene by utilizing an electrochemical reaction. Specifically, the invention provides an electrochemical anodic oxidation cathode reduction characteristic instead of a traditional chemical oxidation reducing agent, sodium difluoromethanesulfinate is used as a difluoromethyl donor, and a difluoromethyl free radical is excited through electrochemical anodic oxidation, so that the difluoromethyl free radical is synthesized. The preparation of the target molecule 2-aryl-3-difluoromethyl benzothiophene is realized through intramolecular cyclization initiated by addition of free radicals to active alkyne. The method does not need to add an additional transition metal catalyst and a super-stoichiometric redox agent, has the advantages of mild reaction conditions, high product yield, good chemical selectivity and the like, better conforms to the purpose of green and sustainable development of the current society, and has a good industrial application prospect.

The invention provides a method for controlling activity of deoxyribozyme through intramolecular cyclization and application of the method, and relates to application of the method in the field of biological analysis and regulation. According to the method, a ring-forming chain is subjected to intramolecular connection mainly through T4DNA ligase and a splint chain to form a ring-shaped molecule, so that active conformation cannot be formed, and catalytic activity cannot be lost. Meanwhile, by modifying functional elements (such as photosensitive groups, disulfide bonds and the like) on the deoxyribozyme, the annular deoxyribozyme can be opened and converted into a linear structure under specific conditions (such as illumination, a reducing agent and the like), so that the catalytic activity of the annular deoxyribozyme is recovered. The cyclic deoxyribozyme molecule has a good enzyme digestion resistant effect and biological stability. The method is simple and efficient, can be used for controlling the catalytic activity of deoxyribozyme in living cells, realizes space-time selective sensing analysis and metabolism regulation of target biomolecules, and is extremely high in application value.

The invention provides a synthesis method of celacarburine and a key intermediate thereof, which comprises the following steps: taking methyl 4-aminobutyrate hydrochloride as an initial raw material, and sequentially carrying out o-nitrobenzenesulfonyl protection, alkylation, amide condensation, hydrolysis and deprotection, intramolecular cyclization, removal of o-nitrobenzenesulfonyl protecting group and optional acylation reaction to obtain a target product. A synthetic route is designed through an innovative strategy, the technical bottlenecks that raw materials and reagents are difficult to obtain, steps are tedious, conditions are harsh, the yield is low and the like which commonly exist in an existing macrocyclic synthesis method are overcome, and the target product is simply and safely prepared in a high-yield mode under the mild condition. The method has the advantages of cheap and easily available raw materials and reagents, simple operation, mild conditions and no need of special equipment, has significant industrial application potential, and provides a stable and reliable material basis for subsequent pharmacological research and new drug development of celacarflurine.

The application provides a synthesis method of celacarfurine and key intermediates thereof, comprising the following steps: taking 4-amino butyric acid methyl ester hydrochloride as a starting material, sequentially performing ortho-nitrobenzenesulfonyl protection, alkylation, amide condensation, hydrolysis and deprotection, intramolecular cyclization, deprotection of ortho-nitrobenzenesulfonyl, and optional acylation to obtain a target product. The synthesis route is designed by an innovative strategy, and overcomes technical bottlenecks such as difficulty in obtaining raw materials and reagents, long steps, harsh conditions and low yield which exist in the existing macrocycle synthesis method, and the target product is prepared under mild conditions with high yield, simplicity and safety. The method is simple in operation, mild in conditions, and does not need special equipment, has significant industrial application potential, and provides a stable and reliable material basis for subsequent pharmacological research and new drug development of celacarfurine.

The present invention relates to a carbonyl reductase mutant and its application in preparing a key intermediate of diltiazem, belonging to the field of bioengineering technology. Specifically, it relates to a carbonyl reductase mutant derived from Candida parapsilosis with significantly improved specific activity, its encoding nucleic acid, a recombinant expression vector and a recombinant expression transformant containing the recombinant carbonyl reductase mutant gene, and the use of the carbonyl reductase mutant as a catalyst in preparing the key intermediate of diltiazem, 2-chloro-3-(4-methoxyphenyl)-3(S)-hydroxypropionic acid methyl ester. Compared with the parent enzyme, the carbonyl reductase mutant of the present invention catalyzes asymmetric reduction to prepare the chiral hydroxy compound 2-chloro-3(S)-hydroxy-3-phenylpropionic acid methyl ester. The chiral hydroxy compound can further generate the cardiovascular drug diltiazem chiral intermediate methyl glycidyl (2R, 3S)-p-methoxyphenyl glycidyl ester through intramolecular cyclization, which has good industrial application prospects.

The present invention relates to a novel synthetic procedure utilizing domino Knoevenagel- cyclization reactions, in which the furan, thiophene or pyrrole subunits of the substrates undergo a Diels-Alder cycloaddition as either a diene or a dienophile producing novel condensed tetra- penta- or hexacycles with bridged or spirocyclic dihydrofuran, -thiophene or -pyrrole moiety. The five-membered aromatic heterocyclic subunit reacts intramolecularly as a diene with the double bond in a [4+2] or [4+4] cycloaddition (1,4-addition to five-membered heterocycle) producing bridged scaffolds. The cyclization step can also be an intramolecular hetero Diels- Alder reaction, in which a heterodiene reacts intramolecularly with the π-excessive five- membered heterocycles acting as a dienophile in the 1,2-addition. Some of the novel condensed heterocyclic products have antiproliferative activity and thus both the compounds and their therapeutic application are subject of the invention.

The invention discloses a method for synthesizing loxapine succinate, which comprises the following steps of: carrying out substitution reaction by using 2-nitrofluorobenzene and 2-hydroxy-4-chloromethyl benzoate as raw materials to generate 5-chloro-2-(2-nitrophenoxy) benzoate; nitryl is reduced, and 5-chloro-2-(2-aminophenoxy) benzoate is generated; the method comprises the following steps: carrying out an intramolecular ring closing reaction to generate 2-chlorodibenzo [b, f] [1, 4] oxazepine-11 (10H)-ketone; 2, 11-dichlorodibenzo [b, f] [1, 4] oxazepine is obtained through a reaction and chlorination; the method comprises the following steps: carrying out a C-N coupling reaction of methyl piperazine to generate 2-chloro-11-(4-methylpiperidine-1-yl) dibenzo [b, f] [1, 4] oxazepine; and salifying with succinic acid to generate the loxapine succinate. The method is easily available in raw materials, simple in process and suitable for large-scale production.

Provided is a thermosetting resin composition with which it is possible to obtain a cured product in which uneven formation is suppressed. A thermosetting resin composition containing (A) a silane compound having intramolecular cyclization reactivity and (B) a radical-reactive resin.

The invention relates to a preparation method of 4-oxa-7-azaspiro [2.5] octane-6-ketone, and belongs to the field of chemical synthesis of medicines. Hydrochloride of glycine ester is used as a starting material, and 4-oxa-7-azaspiro [2.5] octane-6-ketone is obtained through five steps of protecting group introduction, cyclization, condensation, protecting group removal and intramolecular cyclization reaction and serves as the starting material of the anti-influenza virus medicine and analogues of the anti-influenza virus medicine. The synthesis route is ingenious in design, the use of a palladium catalyst and a harmful reagent chloroacetyl chloride in the prior art is reduced or avoided, and the material cost and the production cost of the whole route are reduced by 70% or above compared with those of the prior art by improving the yield of the two key reactions of condensation and cyclization and simplifying the operation steps. The method is suitable for industrial application.

The invention discloses a metallocene complex and a preparation method thereof.The preparation method comprises the steps that a 2, 5-pentanedione derivative which is cheap and commercially available serves as a starting raw material, a cyclopentenone derivative is generated through alkali catalytic intramolecular cyclization, then the cyclopentenone derivative reacts with a Grignard reagent to generate a cyclopentadiene derivative, and the metallocene complex is obtained. And finally, protons are captured through sodium hydride and then react with zirconium chloride to obtain the metallocene complex, compared with some routes with complex initial raw materials or routes related to medicine control, reagents involved in the reaction process are commercially available cheap raw materials, the reaction conditions are mild, the method is suitable for industrial production, and the method further has the amplified production potential.

The invention belongs to the field of organic chemical synthesis, and relates to a method for synthesizing a natural product Pyrroloazocine indole alkaloid skeleton. According to the method, a commercially available compound 1 and phenylhydrazine are taken as synthesis starting points, and a [2.2. 2] bridge ring system is constructed through key Fischer indole synthesis, Stille coupling reaction and intermolecular Diels-Alder reaction. The preparation method comprises the following steps: carrying out a cyclopropanation reaction mediated by carbene, carrying out a Ley-Griffith oxidation reaction, and carrying out a Beckmann rearrangement and an intramolecular SN2 cyclization cascade reaction so as to realize the construction of the core skeleton of the Pyrroloazocine indole alkaloid. According to the method, a material basis can be provided for activity testing of the Pyrroloazocine indole alkaloid and the analogue thereof, and a thought is provided for synthesis route design of more complex cage-shaped indole alkaloid basic frameworks.

This invention discloses a method for synthesizing 3-oxa[3.1.1]spiropropane, belonging to the fields of organic synthetic chemistry and medicinal chemistry. This method is the first to introduce oxygen atoms into the high-strength skeleton of [3.1.1]spiropropane, successfully synthesizing the 3-oxa[3.1.1]spiropropane molecule. The specific synthetic route is as follows: starting with 3,3-bis(bromomethyl)oxacyclobutane, the 3-oxabicyclo[3.1.1]heptane diol skeleton is constructed sequentially via nucleophilic substitution with diethyl malonate, reduction, and intramolecular cyclization. Then, oxidation and Barton decarboxylation iodination are performed to obtain the key intermediate 1,3-diiodo-3-oxabicyclo[3.1.1]heptane, which is finally reacted with an organolithium reagent to obtain the target product. This invention fills a technological gap in the synthesis of heteroatom-substituted spiroalkyl, providing a key precursor for the subsequent development of its free radical bifunctionalization reaction and the construction of structurally diverse 3-oxabicyclic [3.1.1]heptane dominant skeletons. It has important application prospects in drug design, especially as a bio-electroisoster of meta-substituted aromatics.

The invention belongs to the technical field of organic synthesis, and provides a multifunctional naphthalene derivative as well as a preparation method and application thereof. In the structural formula of the multifunctional naphthalene derivative, R2 is alkyl, phenyl, 2-naphthyl, 1-naphthyl, 2-thienyl, an aromatic ring connected with an electron withdrawing group or an aromatic ring connected with an electron donating group, and the electron withdrawing group and the electron donating group comprise methyl, methoxyl, trifluoromethyl or halogen; r3 is H, methyl or methoxyl; r4 is H, methyl, phenyl or alkynyl. According to the preparation method, a 1, 6-diyne-3-alcohol compound is taken as a raw material, [2-(di-tert-butylphosphine) biphenyl] gold chloride (I) and silver tetrafluoroborate are taken as catalysts, intramolecular 6-endo-dig cyclization, 3, 3-Claisen rearrangement and aromatization reaction are performed, and finally, deacylation reaction is performed to obtain the multifunctional naphthalene derivative with phenyl, phenylethynyl and naphthalene ring structures. The method has application value in multiple fields.

The invention discloses a preparation method of irisone, which comprises the following steps of: performing condensation reaction on citral (compound II) serving as a raw material and acetone to obtain pseudoionone (compound III); the preparation method comprises the following steps: carrying out a cyclopropanation reaction with diethyl zinc and diiodomethane under the action of a catalyst to obtain a compound IV, carrying out an intramolecular cyclization reaction on the compound IV under the action of the catalyst, and carrying out post-treatment to obtain a compound I. The route is mild in reaction condition, simple and convenient to operate, stable in process and good in reaction selectivity; the proportion of alpha-irisone in the crude product of the compound I is high, the total yield can reach 78%, and the method is suitable for large-scale industrial production.

The present invention belongs to the field of organic chemical industry, and particularly relates to a method for synthesizing 7,8-dihydroindazin-5(6H)-one. Using O-acetyl ketoxime and 2-alkyl-substituted cyclohexanedione as raw materials, under the catalysis of a copper salt, heating to 80-120 °C in a nitrogen atmosphere, various substituted 7,8-dihydroindazin-5(6H)-one derivatives are obtained in one step through consecutive C-C radical coupling, intramolecular cyclization, and rearrangement reactions. The raw materials and catalysts used in the present invention are cheap and easily available, the substrate range is wide, and the functional group compatibility is good. This method has many advantages such as a short synthesis route and convenient separation and purification, and has important practical application value for the synthesis of 7,8-dihydroindazin-5(6H)-one derivatives.

The present invention provides a hydrogenation-responsive coenzyme NAD(P)H fluorescent probe, a preparation method, a fluorescent sensor and an application, and belongs to the technical field of fluorescent probes. In the presence of NAD(P)H, the trimethylbenzoquinone functional group in the molecule of the hydrogenation-responsive coenzyme NAD(P)H fluorescent probe prepared by the present invention can be catalytically reduced to a responsive trimethylhydroquinone by an organic metal iridium or organic metal rhodium catalyst. The generated trimethylhydroquinone will rapidly undergo intramolecular cyclization and fall off from the probe molecule, turning on the fluorescence of the probe molecule, thereby achieving a rapid and efficient fluorescent response to NAD(P)H. The hydrogenation-responsive coenzyme NAD(P)H fluorescent probe of the present invention has a stable structure, high fluorescence quantum yield, a wide pH adaptability range, good biocompatibility, and mitochondrial targeting. When combined with highly active organic iridium and rhodium catalysts, it can quickly, sensitively and specifically detect the coenzyme NAD(P)H with a detection limit of 1.0 μM.