47 results about "Tabersonine" patented technology

The invention provides a half synthetic method for industrially producing vinpocetine on the premise of ensuring product purity and yield. Voacanga seed grown in Africa is used for extracting raw material-tabersonine required by synthesis. The tabersonine is synthesized into vinpocetine by four steps: 1) preparing vincadifformine; 2) preparing vincamine; 3) preparing vincamine acid; and 4) synthesizing the vinpocetine the content of which is 99%. The invention builds an integral process from tabersonine to vinpocetine, has the advatages of simple process, high yield and lower cost, and can realize the industrial production of vinpocetine on the premise of ensuring the product purity and yield.

The invention relates to a preparation method of plant extract, in particular to a preparation method of willow leaf tabersonine, which can resolve the problems of prior art such as complex process, long production period and low product yield. The preparation method comprises 1, material pretreatment: breaking and drying seeds, 2, heating, refluxing, extracting and acidifying, 3, purifying on column, 4, alkalizing, extracting, washing hexane layer via water and removing solvent to obtain the product. The preparation method has the advantages of simple chemical process, low environment pollution, high safety, short production period, support for large-scale industrial production, simple process, high controllability and high product yield, wherein unit kilogram of Africa potato can produce at least 98% willow leaf tabersonine whose yield is higher than 1.6%.

The invention relates to a semisynthesis process route which takes tabersonine salt as raw material for producing vincamine. Catalytic hydrogenation, peroxidation, rearrangement, crystallization and recrystallization are sequentially performed on the tabersonine salt for getting the high-purity vincamine, and the content is greater than 99.0%. Calculated according to the tabersonine salt, the overall yield of the vincamine is 55.3%. The method has the characteristics of low cost, high yield, short time, and simplicity and safety in operation, and is completely applicable to industrialized large-scale production.

The invention discloses a process for preparing tabersonine, aiming at solving the problems of tedious process, higher cost, lower yield and the use of solvents serious harmful to human bodies in the prior art. The process comprises the steps of: crushing raw materials, extracting with acid water, alkalizing and extracting the extracting solution, mixing an organic extraction layer, concentrating, recycling until no solvent exists, placing in a refrigerator, standing overnight, precipitating crystals, centrifuging, and drying the crystals. In method disclosed by the invention, the properties of alkaloid are utilized for acidizing tabersonine into salt with a water extraction process, thus, the production steps are simplified, and the production cost is reduced; the method has the advantages of simple process and easiness for operation, the yield is largely improved by about 3%, and the products are light yellow powder and have higher quality; and in addition, because less solvent is used, the pollution to the environment and the harm to human bodies are lowered.

The invention provides antineoplastic active ingredient tabersonine derivative, as is shown in formula (I), pharmaceutical compositions, and the preparing method and the medical application thereof.

The invention relates to the plant extraction field, and aims to provide an efficient and environmentally-friendly technology for extracting tabersonine from Voacanga chalotiana Pierre ex Stapf. The technology comprises the following steps: 1, taking Voacanga chalotiana Pierre ex Stapf, sun-drying, peeling shells, and crushing; 2, micronizing treatment: adding submicron powder obtained in step 1 into ethyl acetate having a volume 1.5-3 times the mass of the submicron powder, and carrying out ultrasonic treatment at normal temperature for 0.5-1h, and centrifuging; 3, carrying out reflux extraction of the filter residue obtained in step 2 for 0.5-2h twice by utilizing ethyl acetate having a volume 2-5 times the mass of the filter residue; 4, mixing the obtained reflux extract liquid with the obtained centrifugate obtained after the ultrasonic treatment, and concentrating until no droplets drop; 5, adding an aqueous solution containing 6-10% of TritonX-114 having a volume 0.5-3 times the volume of the concentrate obtained in step 4, carrying out heat insulation stirring at 35-50DEG C for 0.5-1h, and centrifuging; and 6, adding a proper amount of water to the solid obtained in step 5, stirring for 10-20min, allowing the obtained solution to stand for separating out the upper layer yellow oil, and extracting 1-3 times by using the above same method, wherein the yellow oil is liquid tabersonine. The technology has the advantages of ingenious combination, high total extraction efficiency and less pollution emission.

The invention relates to a semi-synthesis process for producing vincamine by taking tabersonine as a raw material. The high-purity vincamine with the content of over 99.0 percent is obtained by performing catalytic hydrogenation, peroxidation, rearrangement, crystallization and recrystallization on the tabersonine. Based on the tabersonine, the total yield of the vincamine is 55.3 percent. The semi-synthesis process has the characteristics of low cost, high yield, short time and simple and safe operation, and is completely suitable for industrialized mass production.

The invention discloses a method for extracting tabersonine from Voacanga Africana seeds. The method comprises the following steps: (1) crushing: crushing the dried Voacanga Africana seeds, screening the crushed seed by a 20-40 mesh screen to obtain powder, grinding the powder by liquid nitrogen to obtain superfine powder; (2) enzymolysis: adding the superfine powder obtained in the step (1) into a cellulase liquid with the enzyme concentration of 0.5-0.7 g / L, allowing the mixture to perform enzymolysis reaction for 2-3 hours at 40-45 DEG C, so as to obtain enzymatic hydrolysate; (3) carrying out supercritical extraction; (4) carrying out alcohol extraction; (5) carrying out separating and purifying. According to the extraction method, toxic solvents such as benzene and chloroform are not used, and no large amount of waste water is generated, and the environment is not polluted, meanwhile, the extraction method is simple to operate, short in time consumption, high in yield and purity, the yield is up to 3.9%, and the purity is 99.6%.

The invention relates to a vincamine preparation method in the field of compound preparation. The vincamine preparation method includes the steps of (1), tabersonine preparation, (2), vincadifformine preparation, (3), monoperoxy maleic acid preparation and (4), vincamine preparation. The vincamine preparation method has the advantages of easy availability to raw materials, simplicity and convenience in reaction process operation, high safety, low cost, high product yield, high quality and suitability for industrial production.

The invention relates to a preparation process of alkaloid tabersonine, relating to the technical field of biopharmaceuticals. The traditional biological preparation process of the tabersonine has the problems of large solvent loss amount, high cost, large water consumption, high adsorbent resin price, and the like. The preparation process of the alkaloid tabersonine, disclosed by the invention, comprises the following steps of: squeezing voacanga seeds; carrying out solvent extraction; carrying out acid water extraction and washing; and carrying out acid water purification, alkalinization and extraction. According to the preparation process disclosed by the invention, solvent dimethylbenzene which has high boiling point, low cost and easiness in obtaining is adopted as an extractant, anda mode of the acid water extraction and washing is adopted, and therefore, the using amount and the treatment capacity of acid water are reduced; extracted diluted acid water is treated by adopting the dimethylbenzene, and therefore the adsorption washing or repeated salt transformation purification process of the conventional macroporous resin is saved; the content of the tabersonine reaches more than 98 percent, and the extraction ratio is between 1.8 percent and 2.0 percent; in addition, according to the invention, production cost is reduced, and water consumption and solvent consumption are reduced.

The invention discloses a semisynthetic production method of vinpocetine, a tabersonine hydrochloride is used as a raw material, Pd / C is used as a catalyst, tabersonine hydrogenation hydrochloride is obtained under normal temperature and pressure, monoperoxy maleic acid is prepared by use of hydrogen peroxide, vincamine is prepared by oxidation, reduction, transposition, settlement and washing then, and the vincamine is hydrolyzed, dehydrated and converted into vinpocetine. The semisynthetic production method of vinpocetine is simple in operation and high in safety, increases the yield, and reduces production cost, and a high purity product can be obtained without column chromatography.

The invention discloses a method for extracting tabersonine from voacanga africana. The method comprises the following steps: S1, crushing a raw material; S2, soaking, namely soaking crushed voacangaafricana fruit seeds into a 2-4% sulfuric acid solution; S3, performing percolation, namely putting the soaked voacanga africana fruit seeds into a percolation tube, continuously adding the sulfuric acid solution from an upper part, and collecting a percolation liquid; S4, filtering, namely filtering the obtained percolation till the filtrate is clear and transparent; S5, performing column chromatography, namely adsorbing the filtrate with a macroporous resin, washing the resin with water when the content of an effluent is greater than or equal to 0.2mg / ml, and collecting a desorption liquid,wherein a 65-75% ethanol solution is adopted as a desorption solvent; S6, performing concentration centrifugation, namely concentrating the desorption liquid, adjusting a pH value, leaving to stand, and performing centrifugation, so as to obtain a product. The method disclosed by the invention is simple and convenient to operate, environmentally-friendly and high in extraction recycling rate.

A preparation method of a vinpocetine analogue comprises the following steps: using UHP (urea hydrogen peroxide) for selective oxidation of a tabersonine analogue, then performing reduction, rearrangement, crystallization, and the like; or using the UHP for selective oxidation of a tabersonine reduction analogue (vinca-fuming analogue), then performing rearrangement, crystallization, and the like to obtain the vinpocetine analogue. Compared with the prior art, the preparation method has the advantages of high yield, direct quantification, simple operation, mild reaction conditions, suitability for industrial production, the yield reaching over 87%, more than 99% of HPLC (high performance liquid chromatography), a white product, good quality and low preparation cost.

The invention discloses a preparation method of high-purity vinpocetine. The preparation method comprises the following steps: S1, preparing vincamine, wherein tabersonine is dissolved, a hydrogenation reaction is performed under the catalysis of palladium and carbon to obtain vincadifformine, the vincadifformine is oxidized to obtain a vincadifformine nitric oxide, and an intermediate vincamine is obtained from the vincadifformine nitric oxide reaction liquid under the catalysis of an acid; S2, dewatering the vincamine by using toluene as a solvent and adding a dewatering agent to obtain apovincamine; and S3, on the basis of the step S2, carrying out a transesterification reaction by taking ethanol as a solvent, using dichloromethane as a cosolvent and using sodium ethoxide / sodium methoxide as a catalyst to obtain a vinpocetine crude product, and re-crystallizing with ethanol to obtain vinpocetine. The process provided by the invention has the advantages of simple production operation, avoidance of high-toxicity reagents, less impurity of the obtained product, high production efficiency, simple and convent operation and environmental friendliness, wherein the purity of the productis more than 99.9%, the quality of the product is higher than the quality of the product obtained by the original research factory, and the medicinal requirements are met.

The invention provides an application of tabersonine in preparing medicines for preventing and treating cancers. The tabersonine can be used for effectively preventing and treating the cancers. According to the invention, the tabersonine is used for preventing the cancers on the basis of the principle that the tabersonine has an obvious inhibitory effect on proliferation of cancer cells, so that the cancer cells become shrunken and diminished in volume, accompanied with karyopyknosis, and finally, cancer cell apoptosis is achieved. Based upon a cytotoxicity test, IC50 value of an inhibitory effect of the tabersonine on a hepatoma cell line SMMC7721 is 12.866-13.230 [mu]mol / L and IC50 value of an inhibitory effect of the tabersonine on a hepatoma cell line Bel7402 is 14.810-15.342 [mu]mol / L, IC50 value of an inhibitory effect on a gastric carcinoma cell line SGC7901 is 11.696-11.910 [mu]mol / L, IC50 value of an inhibitory effect on an ovarian carcinoma cell line SKOV3 is 24.383-24.703 [mu]mol / L and IC50 value of an inhibitory effect on an ovarian carcinoma cell line Hey is 14.669-14.977 [mu]mol / L, showing that the tabersonine has an excellent effect of preventing and treating the cancers.

The invention discloses a method for extracting tabersonine from voacanga seeds. The method comprises the steps: 1, utilizing 50% to 95% ethyl alcohol to ultrasonically extract 3 times to obtain ethanol extract, wherein once extraction is performed for 0.5 to 1 hour; 2, utilizing an organic solvent to extract the ethanol extract 3 to 5 times to obtain organic extractant, wherein once extraction is performed for 3 to 5 hours; 3, utilizing HPD-100 macroporous resin to elute the organic extractant to obtain ethanol eluate; 4, adding acid into the ethanol eluate to extract the ethanol eluate to obtain acid extractant; 5, adding alkali liquor into the acid extractant to adjust the pH value to the alkaline degree and then adding chloroform to extract to obtain tabersonine. The method is simple and low in cost and can effectively improve the extraction purity and yield of the tabersonine.

The invention relates to a synthetic process for chemical medicines, in particular to a process for preparing vincamine by a semisynthetic method. At present, the process for preparing the vincamine is divided into a total synthetic method and the semisynthetic method, wherein the semisynthetic method has the problems of unstable and inflammable hydrogenation catalyst, large using amount, high hydrogenation pressure, insecurity in the preparation of monoperoxide maleic acid and the like. The process comprises the following steps of: preparing tabersonine vincadifformine hydrochloride, preparing the monoperoxide maleic acid, performing oxidizing reaction, performing reduction reaction and transposition reaction, precipitating ammonia and purifying products, wherein the low-cost and stable Pd / C hydrogenation catalyst is selected to reduce the pressure of the hydrogenation reaction; tabersonine sulfate is replaced by the tabersonine hydrochloride; the monoperoxide maleic acid is preparedby using low-concentration hydrogen peroxide; the reaction temperature is below 0 DEG C, and security coefficients are improved; the temperature of the oxidizing reaction is reduced, and the generation of isomers is reduced; purification and solvent recrystallization are performed by column chromatography; and the quality of the products reaches the pharmaceutical-grade standard.

The invention relates to a preparation method of plant extract, in particular to a preparation method of willow leaf tabersonine, which can resolve the problems of prior art such as complex process, long production period and low product yield. The preparation method comprises 1, material pretreatment: breaking and drying seeds, 2, heating, refluxing, extracting and acidifying, 3, purifying on column, 4, alkalizing, extracting, washing hexane layer via water and removing solvent to obtain the product. The preparation method has the advantages of simple chemical process, low environment pollution, high safety, short production period, support for large-scale industrial production, simple process, high controllability and high product yield, wherein unit kilogram of Africa potato can produce at least 98% willow leaf tabersonine whose yield is higher than 1.6%.

The invention discloses a method for extracting tabersonine from Voacanga Africana seeds. The method comprises the following steps: (1) crushing: crushing the dried Voacanga Africana seeds, screening the crushed seed by a 20-40 mesh screen to obtain powder, grinding the powder by liquid nitrogen to obtain superfine powder; (2) enzymolysis: adding the superfine powder obtained in the step (1) into a cellulase liquid with the enzyme concentration of 0.5-0.7 g / L, allowing the mixture to perform enzymolysis reaction for 2-3 hours at 40-45 DEG C, so as to obtain enzymatic hydrolysate; (3) carrying out supercritical extraction; (4) carrying out alcohol extraction; (5) carrying out separating and purifying. According to the extraction method, toxic solvents such as benzene and chloroform are not used, and no large amount of waste water is generated, and the environment is not polluted, meanwhile, the extraction method is simple to operate, short in time consumption, high in yield and purity, the yield is up to 3.9%, and the purity is 99.6%.

The invention discloses a technological method for detecting tabersonine in voacanga seeds. The technological method includes (1) sampling and crushing; uniformly sampling from various points, uniformly mixing voacanga seed samples and crushing the voacanga seed samples for standby application; (2) extracting: adding 3g of the crushed voacanga seed samples into an extracting tank, further adding 25ml of methanol in the extracting tank, extracting by the aid of ultrasonic waves for 30 minutes, allowing the mixture to stand for 30 minutes and cooling the mixture to reach the room temperature; and (3) detecting liquid phases: taking from 1ml to 10ml of supernate obtained in the step (2) into a measuring flask, metering the supernate to a certain graduation, using the supernate as to-be-tested liquid, respectively precisely metering 5 microliters of comparison liquid with the concentration of 1mg / ml and 5 microliters of the to-be-tested liquid and filling the comparison liquid and the to-be-tested liquid into a liquid chromatograph, and recording the peak area and obtaining the content of the to-be-tested liquid according to a content computational formula. The technological method has the advantages that consumption of raw materials is low, required time is short, accuracy of detection results is high, and relative errors are fewer.

The invention relates to a resin for separating and purifying tabersonine and applications thereof. A novel resin can be obtained by performing chloromethylation based on a commercial resin as a starting resin, and then reacting with amino acid. The novel resin is extremely low in the capability of adsorbing the tabersonine in the acid liquor extracted from voacanga chalotiana pierre ex stapf seeds, and can selectively adsorb impurities in the extracted acid liquor; when the novel resin is used for separating and purifying tabersonine, the steps are as follows: firstly, pretreating and grinding voacanga chalotiana pierre ex stapf seeds, performing heating reflux extraction and acidification through organic solvent, purifying the acid liquor through the novel resin, enabling the target product tabersonine to be enriched remaining upper column liquor and washing liquor, alkalizing, extracting and concentrating the collecting liquor to obtain the product tabersonine. The novel resin is used for separating and purifying tabersonine, the recovery rate of the tabersonine can be improved, high-concentration alcohol washing is not required in the upper column purification process, and the production cost and the solvent usage amount can be reduced.

The invention discloses a medicine composition for treating encephalatrophy and a preparation method of the medicine composition. The medicine composition is prepared from papiliochrome II, whole grass of northern bedstraw, whole grass of thyrocarpus sampsonii hance, neferine, asarinin and tabersonine according to a proportion. The medicine composition can be prepared into various dosage forms according to conventional preparation technologies, and is significant in treatment effect when used for treating encephalatrophy.

The invention discloses a cleaning process for extracting and purifying tabersonine from voacango Africana stapf seeds, belonging to the technical field of preparation of plant extracts. The process is used for extracting the tabersonine from the voacango Africana stapf seeds by adopting a carbon dioxide supercritical extraction technology; after initial separation of acid and alkali treatment and solvent extraction, the tabersonine is purified by using a column chromatography technology; and the obtained tabersonine has the purity of 98% and the yield of more than 2.0%. The cleaning process disclosed by the invention is a high-efficiency environment-friendly process which is high in sample yield, high in purify, simple and safe in process, good in controllability, low in cost and short in production cycle, and is applied to large-scale industrial production.

The invention provides a green preparation method of vincamine, which comprises the following steps: (1) reduction: introducing a tabersonine methanol solution and hydrogen into a micro-channel reactor through a charging pump to react, and filtering, concentrating and extracting the reaction solution twice after the reaction is finished, thereby obtaining an extracting solution; (2) oxidation: catalyzing an organic phase in the extraction liquid in the step (1) by using peroxy acid to carry out oxidation reaction, neutralizing by using a sodium bicarbonate solution after the reaction is finished, extracting and concentrating; and (3) rearrangement: dissolving the concentrated solid obtained in the step (2) with ethanol, rearranging in the presence of a catalyst, adjusting the pH value after the reaction is completed, filtering, washing and crystallizing the filter cake, and separating out the solid, namely vincamine. The preparation method is safe, environmentally friendly and capable of achieving continuous production, the product purity is 99% or above, automatic equipment can be adopted for continuous production, and the industrial production efficiency is improved.

The invention discloses a process for preparing tabersonine, aiming at solving the problems of tedious process, higher cost, lower yield and the use of solvents serious harmful to human bodies in the prior art. The process comprises the steps of: crushing raw materials, extracting with acid water, alkalizing and extracting the extracting solution, mixing an organic extraction layer, concentrating, recycling until no solvent exists, placing in a refrigerator, standing overnight, precipitating crystals, centrifuging, and drying the crystals. In method disclosed by the invention, the properties of alkaloid are utilized for acidizing tabersonine into salt with a water extraction process, thus, the production steps are simplified, and the production cost is reduced; the method has the advantages of simple process and easiness for operation, the yield is largely improved by about 3%, and the products are light yellow powder and have higher quality; and in addition, because less solvent is used, the pollution to the environment and the harm to human bodies are lowered.

The invention discloses a method for extracting tabersonine from voacanga africana. The method comprises the following steps: S1, crushing a raw material; S2, soaking, namely soaking crushed voacangaafricana fruit seeds into a 2-4% sulfuric acid solution; S3, performing percolation, namely putting the soaked voacanga africana fruit seeds into a percolation tube, continuously adding the sulfuric acid solution from an upper part, and collecting a percolation liquid; S4, filtering, namely filtering the obtained percolation till the filtrate is clear and transparent; S5, performing column chromatography, namely adsorbing the filtrate with a macroporous resin, washing the resin with water when the content of an effluent is greater than or equal to 0.2mg / ml, and collecting a desorption liquid,wherein a 65-75% ethanol solution is adopted as a desorption solvent; S6, performing concentration centrifugation, namely concentrating the desorption liquid, adjusting a pH value, leaving to stand, and performing centrifugation, so as to obtain a product. The method disclosed by the invention is simple and convenient to operate, environmentally-friendly and high in extraction recycling rate.

The invention relates to the plant extraction field, and aims to provide an efficient and environmentally-friendly technology for extracting tabersonine from Voacanga chalotiana Pierre ex Stapf. The technology comprises the following steps: 1, taking Voacanga chalotiana Pierre ex Stapf, sun-drying, peeling shells, and crushing; 2, micronizing treatment: adding submicron powder obtained in step 1 into ethyl acetate having a volume 1.5-3 times the mass of the submicron powder, and carrying out ultrasonic treatment at normal temperature for 0.5-1h, and centrifuging; 3, carrying out reflux extraction of the filter residue obtained in step 2 for 0.5-2h twice by utilizing ethyl acetate having a volume 2-5 times the mass of the filter residue; 4, mixing the obtained reflux extract liquid with the obtained centrifugate obtained after the ultrasonic treatment, and concentrating until no droplets drop; 5, adding an aqueous solution containing 6-10% of TritonX-114 having a volume 0.5-3 times the volume of the concentrate obtained in step 4, carrying out heat insulation stirring at 35-50DEG C for 0.5-1h, and centrifuging; and 6, adding a proper amount of water to the solid obtained in step 5, stirring for 10-20min, allowing the obtained solution to stand for separating out the upper layer yellow oil, and extracting 1-3 times by using the above same method, wherein the yellow oil is liquid tabersonine. The technology has the advantages of ingenious combination, high total extraction efficiency and less pollution emission.

A preparation method of a vinpocetine analogue comprises the following steps: using UHP (urea hydrogen peroxide) for selective oxidation of a tabersonine analogue, then performing reduction, rearrangement, crystallization, and the like; or using the UHP for selective oxidation of a tabersonine reduction analogue (vinca-fuming analogue), then performing rearrangement, crystallization, and the like to obtain the vinpocetine analogue. Compared with the prior art, the preparation method has the advantages of high yield, direct quantification, simple operation, mild reaction conditions, suitability for industrial production, the yield reaching over 87%, more than 99% of HPLC (high performance liquid chromatography), a white product, good quality and low preparation cost.

Methods that may be used for the manufacture of a class of chemical compounds known as terpenoid indole alkaloids, including tabersonine and catharanthine are provided. Compositions useful for the synthesis of terpenoid indole alkaloids, including tabersonine and catharanthine are also provided. The provided compounds are useful in the manufacture of chemotherapeutic agents.