33 results about "Indole alkaloid" patented technology

The invention provides a planting method for promoting synthesis of camptothecin and derivatives thereof from nothapodytes pittosporoides. The planting method comprises the following steps: planting a plurality of nothapodytes pittosporoides trees in a planting field; organic fertilizer is applied to the multiple planted nothapodytes pittosporoides trees every first preset time; the planted nothapodytes pittosporoides trees are soaked with cold water for several days, and temperature and water stress is carried out; removing the nothapodytes nothapodytes which do not survive after water stress; introducing microorganisms every second preset time to adjust rhizosphere microorganisms of the nothapodytes pittosporoides trees so as to carry out microorganism stress; watering is stopped in autumn, so that the survival nothapodytes nothapodytes trees are subjected to sunlight stress, and the survival nothapodytes nothapodytes trees enter the sunlight stress period; in the sunlight stress period, synthesis of terpene indole alkaloid of rhizosphere microorganisms is activated, and synthesis of camptothecin and derivatives of camptothecin from nothapodytes pittosporoides is promoted; wherein except for the sunlight stress period, the environment temperature of the planting field is kept at 5 DEG C or above, and the environment humidity is kept at 63%-78%.

This invention belongs to the technical field of chemical drug synthesis, specifically relating to an indole alkaloid compound, its preparation method, and its application. The indole alkaloid compound, whose structural formula is shown in Formula I, is synthesized from 7-bromoindole and a boric acid ester as starting materials. The preparation process is simple and easy, and the resulting indole alkaloid compound or a pharmaceutically acceptable salt thereof exhibits highly effective targeted inhibition of STEAP1, inhibiting STEAP1 at both the protein and cellular levels and demonstrating potent anti-proliferative effects against prostate cancer cells in animals.

The invention discloses a method for preparing isopentenyl indole alkaloid Debromolustramine B. The isopentenyl indole alkaloid Debromolustramine B belongs to the technical field of organic synthesis, an o-bromo aniline aldehyde compound is used as an initial raw material, and on the basis of novel chiral p-toluene sulfinyl guidance, cheap copper catalysis amido alpha-position arylation and 3, 3-dimethyl allyl bromide cyclization reaction, the isopentenyl indole alkaloid Debromolustramine B is synthesized, and the isopentenyl indole alkaloid Debromolustramine B is obtained. According to the present invention, the key aryl quaternary carbon chiral center in the isopentenyl indole alkaloid Debomolustramine B is constructed, and the isopentenyl indole alkaloid Debomolustramine B with the butyrylcholine esterase inhibition activity is prepared through the subsequent series of chemical conversion, such that the material basis is provided for the further research of the natural product Debomolustramine B and the analogue thereof. The method has the advantages that the reaction conditions are mild, the cheap metal copper is used as the catalyst, the synthesis route is short, the energy consumption is low, the environmental protection is facilitated, and the large-scale chiral preparation of the isopentenyl indole alkaloid Debromofloutramine B is facilitated; the method also has the characteristics of relatively good atom economy and high product yield.

The application discloses a steroid-indole alkaloid hybrid dimer compound, a preparation method thereof and application of the compound in preparation of an antitumor chemotherapy drug sensitizer, and first prepares the steroid-indole diketopiperazine alkaloid hybrid compound from a fungus Aspergillus sp. EGF15-0-3 rice culture medium. The compound is a new skeleton compound first discovered in nature. It is first discovered that the hybrid compound has Tdp1 inhibitory activity and can be applied as a tyrosine-DNA phosphodiesterase 1 (Tdp1) inhibitor. It is first discovered that the hybrid compound has chemotherapy sensitization activity on a tumor chemotherapy drug topotecan TPT, which provides a drug source molecule and data support for development of a new natural antitumor combination inhibitor, and has important significance for development and utilization of marine Aspergillus sp. fungus resources.

The invention discloses a biphenyl-diketopiperazine indole alkaloid hybrid compound, which is separated from a fermentation product of a strain Aspergillus candidus HNNU0546, and has a skeleton molecule formed by hybridizing rare diketopiperazine indole alkaloid with biphenyl molecules through an isopentenylation branch chain, and the biphenyl compound can obviously inhibit the activity of crop disease fungi.

The application discloses a synthesis method and application of an indole alkaloid derivative. The method uses 5-aminoindole or 6-aminoindole as a substrate, reacts with acyl chloride or carboxylic acid to obtain an intermediate, and then reacts with Hydroxyclavatol to obtain a Penindolone (PND) derivative of the application. The method has the advantages of easy availability of raw materials, short reaction time, few steps involved, simple post-treatment and the like. The indole alkaloid PND derivative prepared by the method has good anti-influenza virus activity and wide application prospect.

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.

The invention provides a preparation method of a natural product indole alkaloid TMC-205, which comprises the following steps: introducing-COCF3 to the 3-site of indole, hydrolyzing-COCF3 to generate TMC-205 or introducing-CHO to the 3-site of indole, and then introducing-CHO to the 3-site to carry out two lines of Pinnick oxidation to generate TMC-205, by establishing an intermediate, the selectivity is high, the side reaction is extremely few, the problem of low yield caused by direct introduction of carboxyl is solved, and the preparation method is suitable for industrial production. According to the present invention, the method can achieve the quantitative and efficient conversion into the carboxyl group, the use of the high toxicity, the high flammability and the expensive reagent in the traditional method is avoided, and in the key step of constructing the core isoprene structure, the 6-bromoindole with the simple structure is innovatively adopted to directly carry out the Heck-dehydration reaction, such that the potential side reaction is effectively reduced, and the cost is reduced; therefore, the product yield is remarkably improved, and the method is suitable for industrial large-scale production.

The invention discloses a monoterpene indole alkaloid compound as well as a preparation method and application thereof, and belongs to the technical field of medicines. The monoterpene indole alkaloid compound disclosed by the invention is separated from ervatamia palmata, has remarkable activity for repairing podocyte injury under the hypoxia condition, and can be used for preparing a medicine for treating chronic renal injury under the hypoxia condition. The traditional Chinese medicine composition has relatively high economic benefits aiming at the current situation of non-hypoxia chronic kidney injury specific medicines.

The application discloses application of an indole alkaloid compound and derivatives in preparation of anti-liver cancer drugs and belongs to the technical field of biological medicines. A structural formula of the indole alkaloid compound is shown in the following formula: the indole alkaloid compound in the application is separated from a medicinal plant Ampelopsis megalophylla Planch, and a series of derivatives (salts) are obtained through derivation or chemical preparation, the compounds can inhibit the effect of HepG 2 human liver cancer cells, and have the drug development potential for preventing or treating liver cancer.

The invention relates to the technical field of indole alkaloid synthesis, and discloses a low-cost short-path indole alkaloid synthesis method, which comprises: mixing o-nitrobenzene acetaldehyde, a substituted amine compound and an active methylene compound according to a molar ratio of 1: (1.0-1.5): (1.0-1.2), adding a catalyst, an alkali and a solvent, carrying out a stirring reaction for 2-6 h at a temperature of 40-80 DEG C, and carrying out filtration, washing and drying to obtain the indole alkaloid. Performing post-treatment to obtain a nitro-substituted indole precursor; and mixing the nitro-substituted indole precursor with a reducing reagent according to a molar ratio of 1: (2.0-3.0), carrying out a reaction at 60-80 DEG C for 2-3 h, and carrying out post-treatment to obtain the indole alkaloid. The synthesis method is short in path, low in cost, mild in condition and suitable for industrial production.

The present invention relates to microorganisms for producing monoterpene indole al-kaloids (MIAs) and derivatives thereof de novo, including halogenated MIAs and halo-genated derivatives thereof. Also provided herein are methods for producing MIAs and derivatives thereof de novo, in particular halogenated MIAs and derivatives thereof, in a 5 microorganism, as well as useful nucleic acids, vectors and host cells for performing the present methods.

The application discloses an indole alkaloid compound, a preparation method and application thereof in preparation of a medicine for treating chronic kidney disease, and the structure of the indole alkaloid compound is shown as formula I. The new indole alkaloid compound is extracted from fruits of a plant for the first time, the compound can significantly reverse the increase of alpha-smooth muscle actin, type I collagen and vimentin expression in HK-2 cells induced by TGF-beta, and the compound shown as formula I has a drug development potential for preventing or treating chronic kidney disease, in particular, anti-kidney fibrosis, at a concentration of 10 muM.

The present invention relates to indole alkaloids from Brucea javanica, their preparation methods, and applications, belonging to the field of pharmaceutical technology. Specifically, the invention relates to two indole alkaloid derivatives extracted and isolated from Brucea javanica, a plant of the genus Simarthaceae. These derivatives exhibit excellent anti-tumor activity. The preparation method of the present invention is simple and easy to implement, has good reproducibility, and is of high purity. #imgabs0#

The invention discloses a method for preparing a 3-carboxylic acid compound through an efficient synthesis route by taking a simple and easily prepared brominated substrate as a starting raw material. Compared with the prior art, the route provided by the invention has the following remarkable advantages: high-activity iodide used in a traditional method is avoided, and the raw material preparation difficulty is reduced; a'one-pot method 'reaction is adopted, so that the operation steps are simplified, and the separation and purification processes of an intermediate product are reduced; reaction conditions are mild, the catalyst is small in dosage, cheap and easy to obtain, and the production cost is reduced; the yield of the derivative is high, the atom economy is good, and the method is suitable for large-scale production. In addition, the indole alkaloid derivative synthesized by the method has potential physiological activity, and an important material basis is provided for related drug development and biological activity research.

A novel hexahydropyrroloindole alkaloid extracted from wolfberry fruit can effectively solve the problems of extracting and preparing novel hexahydropyrroloindole alkaloid A from wolfberry fruit and realizing its application in preparing drugs for preventing and treating type 2 diabetes. The dried wolfberry fruit is heated under reflux for extraction, concentrated, and applied to a macroporous adsorption resin column. The product is eluted with water, ethanol, and acetone in sequence. The ethanol fraction is concentrated under reduced pressure, extracted, mixed with silica gel, gradient eluted, the same fractions are combined, the target component is eluted, mixed with silica gel, gradient eluted, the fractions within the retention time are collected, concentrated, and dried. The application of the prepared novel hexahydropyrroloindole alkaloid A in preparing drugs for preventing and treating type 2 diabetes can significantly promote glucose consumption in insulin-resistant HepG2 cells, improve glucose uptake capacity, promote glycogen synthesis, and enhance the activities of key glycolytic enzymes hexokinase and pyruvate kinase. The development and application prospects are broad and the economic and social benefits are significant.

Disclosed is yeast cells having peroxisomally localized GPP synthase and a peroxisomally localized enzyme that converts GPP into a monoterpenoids, cannabinoids, monoterpene indole alkaloids and prenylated aromatic compounds; or a precursor therefore, which yeast cells are capable of producing improved amounts of monoterpenoids, cannabinoids, monoterpene indole alkaloids and prenylated aromatic compounds, compared with the same yeast cells where the GPP synthase and the enzyme that converts GPP are located in the cytoplasm. Further disclosed is the use of the yeast cell for producing monoterpenoids, cannabinoids, monoterpene indole alkaloids and prenylated aromatic compounds.

The invention relates to application of indole alkaloids in preparation of ferroptosis inhibitors. The indole alkaloid has a structure as shown in a formula (I): # imgabs0 #, wherein R1, R2 and R3 are independently H, C1-6 alkyl, C1-6 alkoxy or C1-6 carboxylic ester. The specific indole alkaloid disclosed by the invention has a remarkable inhibition effect on ferroptosis of neuronal cells, is low in cytotoxicity, and can be used for preparing medicines for treating and / or preventing neurodegenerative diseases and ischemic cerebral apoplexy caused by ferroptosis.

The present invention discloses an indole alkaloid compound, a preparation method and an application thereof. It belongs to the field of microbial pesticide technology. The molecular structure of the indole alkaloid compound, the preparation of related microorganisms and the preparation method are provided. The indole alkaloid compound to which the present invention relates is different from the known indole alkaloid compounds in terms of structural features such as its structural skeleton and cyclization mode. The indole alkaloid compound involved is produced by fermentation of the strain Aspergillus japonicus TE‑739D and is easy to carry out large-scale fermentation production; the preparation method provided by the present invention can quickly and accurately prepare the indole alkaloid compound. It is found for the first time that the indole alkaloid compound has antibacterial activity against drug-resistant gray mold fungi, can significantly inhibit the growth of drug-resistant gray mold fungi, and can be used as a lead compound or a new biopesticide component with the ability to inhibit drug-resistant gray mold fungi.

This invention belongs to the field of pharmaceutical technology, specifically relating to a class of sarpagine-type indole alkaloid derivatives, their preparation methods, and applications. The structural formula of this class of compounds is shown in formula (I). They exhibit good antitumor activity, low toxicity to normal cells, and are safe, effective, and low-toxicity candidate antitumor drugs.

The invention discloses aralia bisindole alkaloid as well as a preparation method and application of the aralia bisindole alkaloid. The prepared aralia plant extract contains at least one of bisindole alkaloids Z-1-Z-21, monomer extraction and cell and animal experiment verification show that the bisindole alkaloid compound can protect nerve cell injury caused by glutamic acid, can improve the epilepsy state and prolong the epilepsy incubation period in an animal model, and can be used for preparing a medicine for treating the epilepsy. The cell arrangement in the brain sea horse area of the epilepsy mouse is improved; the neuron deformation is reduced. In addition, the series of bisindole alkaloid compounds have chemical structure types different from those of existing epilepsy treatment targeted drugs, and have wide application prospects in preparation of novel epilepsy treatment drugs.

The invention discloses a monoterpenoid indole alkaloid compound as well as a preparation method and application thereof. The monoterpenoid indole alkaloid compound has a structure as shown in any one of formulas I to XII. The invention discloses a monoterpenoid indole alkaloid compound found from a medicinal plant gossypium hirsutum, and provides an extraction and separation method, a structure identification method and an anti-inflammatory effect application of the monoterpenoid indole alkaloid compound. The monoterpenoid indole alkaloid compounds 1, 4 and 8 provided by the invention have obvious activity of inhibiting release of LPS-induced RAW264.7 macrophage NO, which proves that the prepared monoterpenoid indole alkaloid compounds have good anti-inflammatory activity and can be used for preparing natural anti-inflammatory drugs.

This invention discloses a mutant of PjTA-R6 transaminase, its construction method, and its applications. Using schizosphingine, a key precursor of large-volume monoterpene indole alkaloids, as the target for reductive amination, this invention rationally designs the PjTA-R6 transaminase through a global free energy optimization strategy, obtaining 10 mutants with significantly higher catalytic efficiencies than the original PjTA-R6 transaminase. Recombinant *E. coli* strains based on these mutants are then constructed, resulting in a substantial improvement in reductive amination catalytic efficiency. The PjTA-R6 L164E / L57F mutant provided by this invention achieves a 99% conversion rate of schizosphingine to bacamargine via whole-cell reductive amination, a 46% increase compared to the original strain. The PjTA-R6 transaminase mutant provided by this invention exhibits significant catalytic efficiency, offering a powerful tool enzyme for overcoming the industrial bottleneck of transaminase catalysis of large-volume substrates, and possesses broad application prospects.

The invention provides an asymmetric preparation method of bisindole alkaloid (S)-6 ''-Debromohaamacanthin A. The method comprises the following steps: carrying out ester group reduction reaction on a compound 1 and lithium aluminum hydride to obtain a compound 2; carrying out azide substitution reaction on the compound 2, 1, 8-diazabicyclo [5.4. 0] undec-7-ene and diphenyl azide phosphate to obtain a compound 3; performing hydrolysis reaction on the compound 2 and a hydrochloric acid solution to obtain a compound 4; the preparation method comprises the following steps: mixing 6-bromoindole with oxalyl chloride to obtain an acyl chloride compound reaction solution; then carrying out acyl chloride substitution reaction on the compound 4, an acyl chloride compound reaction solution and triethylamine to obtain a compound 5; and carrying out Staudinger reduction reaction on the compound 5 and triphenylphosphine, so as to obtain the bisindole alkaloid (S)-6 ''-Debromohaamacanthin A. The invention further discloses a preparation method of the bisindole alkaloid (S)-6''-Debromohaamacanthin A. The invention further provides application, and the target product is used for preparing anti-tumor drugs. The synthetic route is unique in design, mild in reaction condition, high in catalytic efficiency, short in route, few in side reaction and simple and convenient to operate. According to the method, the problems that the source of the natural product (S)-6 ''-Debromohaamacanthin A is limited and the extraction rate is low can be solved.

The anti-tumor pharmaceutical composition derived from the marine symbiotic bacteria comprises an active component A, an active component B and a medicinal carrier, the active component A is indole alkaloid separated from fermentation liquor of the marine symbiotic bacteria Streptomyces sp.M2021-03, and the molecular formula of the indole alkaloid is H21NO4; the active ingredient B is a polyketone compound separated from a fermentation solution of marine symbiotic bacteria Pseudomonas sp.M2021-07, and the molecular formula of the polyketone compound is C24H30O6; the medicinal carrier is a composite carrier of poloxamer 188 and beta-cyclodextrin in a mass ratio of 1: 2. The active component A (indole alkaloid) blocks mitotic division by inhibiting tumor cell microtubule polymerization, the active component B (polyketone compound) can down-regulate VEGF expression and inhibit angiogenesis, and the inhibition rates of MCF-7 and A549 cells are respectively increased by 40% and 35% compared with those of a single component when the two components are combined.

This invention belongs to the field of extraction and separation of traditional Chinese medicine, specifically relating to a method for the extraction and separation of indole alkaloids and its application. The compound is named oleraindolinpyrro, with the molecular formula C2. 12 H 14 N₂O₃, with the structural formula shown in formula (I). This invention employs ethanol reflux extraction, ODS column chromatography, Sephadex LH-20 gel column chromatography, and high-performance liquid chromatography to isolate this compound from Portulaca oleracea with a purity exceeding 96%. Pharmacological experiments show that this compound significantly inhibits the release of IL-1β and TNF-α from LPS-induced RAW264.7 macrophages, exhibiting anti-inflammatory activity. The method of this invention is simple, environmentally friendly, and produces high purity; the obtained compound can be used to prepare anti-inflammatory drugs or as a lead compound for research.

The invention discloses a method for preparing indole compounds through an efficient synthesis route by taking a simple and easily prepared brominated substrate as a starting raw material. Compared with the prior art, the route provided by the invention has the following remarkable advantages: 1, high-activity iodide used in a traditional method is avoided, and the raw material preparation difficulty is reduced; 2, the reaction condition is mild, the operation is simple and convenient, and a complex process harmful to the environment is avoided; 3, the catalyst is small in dosage, cheap and easy to obtain, and the production cost is reduced; and 4, the yield of the derivative is high, the atom economy is good, and the method is suitable for large-scale production.

The invention discloses indole alkaloid natural product derivatives for treating drug-resistant small cell lung cancer as well as a preparation method and application of the indole alkaloid natural product derivatives. According to the method, a benzophenone diphenol derivative intermediate which is simple and easy to prepare reacts with indole to obtain the indole alkaloid natural product derivative; the method has the advantages of easily available raw materials, simple post-treatment and the like; the indole alkaloid natural product derivative prepared by the invention has good in-vivo and in-vitro small cell lung cancer drug-resistant cell activity, and has a wide application prospect.

The invention discloses tryptamine indole alkaloid as well as a preparation method and application thereof. The tryptamine indole alkaloid, the derivatives thereof, the organic and inorganic acid salts, the pharmaceutical composition containing the compounds and the plant extract can effectively treat or prevent diseases with pathological characteristics of lysosomal pathway disorders, including but not limited to anxiety, depression, neurodegenerative diseases, autoimmune diseases and the like, by adjusting TFEB. The tryptamine indole alkaloid can also be used as an IDO and MAOA inhibitor to improve diseases closely related to IDO and MAOA, including but not limited to depression, neurodegenerative diseases, autoimmune diseases and the like.