CN112028895A - Synthetic method of natural product (-) -psychratrisine - Google Patents
Synthetic method of natural product (-) -psychratrisine Download PDFInfo
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Abstract
The invention relates to a synthetic method of a natural product (-) -psycotriasine, which takes a known compound shown in a formula 1 as an initial raw material and adopts trityl protection, Reformatsky reaction and LiAlH4A series of reactions such as reductive cyclization, Buchwald-Hartwig reductive amination and Larock ring closure are carried out to synthesize the target molecule. The whole route of the invention has unique and novel design, mild reaction conditions in the reaction process, high speed, relatively few side reactions and simple and convenient operation, and the route utilizes conventional chemical reagents, has cheap and easily obtained raw materials and can greatly reduce the synthesis cost.
Description
Technical Field
The invention relates to a synthetic method of a key intermediate of a natural product, in particular to a synthetic method of a natural product (-) -psycotriasine.
Background
The dimeric alkaloid (-) -psychotriene was isolated from Psychoria carocapa in 2010 from the Huihoujiang topic group. They then specifically analyzed two parts of psychromeine using one-and two-dimensional nmr hydrogen probes to determine their structure.
The indole skeleton in the Psychotrianine alkaloid is filled in the natural world from the most deep forest to the ocean, from the simplest to the most complex, and the compound with the core skeleton usually shows excellent biological activity clinically, wherein the Psychotrianine, Psychotrimine, Chetomin, Psychotramine, Pestalazine B and the like show good inhibition effect on various cancer cells. To date, studies on the synthesis of (-) -Psychotriasine have been reported by several groups.
The methods for synthesizing the natural product (-) -Psychotriasine reported in the literature at present mainly comprise the following steps: xuebin et al published in Chemical Science 2015 under the heading of endogenous and endogenous azo linking/ionization-cyclations of a unified strand for the total synthesis of (-) -pseudo-yeast and (+) -pestalazine; arijit et al, 2016, published on Organic Letters, entitled research paper of Lewis Acid Catalyzed displacements of trichloroacetic acids in the Synthesis of functional polarized minerals; a research paper entitled Chiral Primary Amine Catalysis for Asymmetric Mannich Reactions of Aldehydes with Ketimeines, Stereoselectivity and Reactivity, published by Zhihui et al in 2017 on Angew. Carefully analyzing the route design and the method of the total synthesis in the prior art has the defects of long synthesis steps, harsh conditions, low construction efficiency, difficult operation of individual reaction, expensive reagent and high toxicity.
Disclosure of Invention
The invention aims to provide a synthetic method of a natural product (-) -psycotriasine, which provides a new synthetic route and takes a known compound shown in a formula 1 as an initial raw material and adopts trityl protection, Reformatsky reaction and LiAlH4A series of reactions such as reductive cyclization, Buchwald-Hartwig reductive amination and Larock ring closure reaction are carried out to synthesize the target molecule.
In order to achieve the purpose, the invention provides a method for synthesizing a natural product (-) -psycotriasine, which comprises the following steps:
(1) dissolving the compound shown in the formula 1 in an N, N-dimethylformamide solvent, adding sodium hydride in batches to enable the solution to become purple, stirring for 1 hour, adding the compound shown in the formula 2 to enable the solution to become yellow, and stirring for 12 hours to obtain a compound shown in the formula 3;
(2) dissolving the compound shown in the formula 3 in dichloromethane, adding (S) - (-) -tert-butyl sulfinamide and tetraethyl titanate, raising the temperature to 50 ℃ to perform condensation reaction, refluxing for 6 hours until the solution turns red, and separating and purifying to obtain the compound shown in the formula 4;
(3) reacting a compound shown in a formula 4 with a compound shown in a formula 5 in a 2-methyltetrahydrofuran solvent environment to obtain a compound shown in a formula 6;
(4) dissolving the compound shown in the formula 6 in dichloromethane at 0 ℃, adding lithium borohydride in batches to perform a reduction reaction, changing the solution from yellow to red, and separating and purifying to obtain a compound shown in the formula 7;
(5) dissolving the compound shown in the formula 7 in dichloromethane at 0 ℃, carrying out oxidation reaction with a dess-martin oxidant at room temperature for 2h, and separating and purifying to obtain a compound shown in the formula 8;
(6) dissolving the compound of the formula 8 in methanol at 0 ℃, adding methylamine hydrochloride, triethylamine and anhydrous magnesium sulfate at room temperature, reacting at room temperature for 12 hours, adding sodium borohydride into the mixture, reacting for 30 minutes, and separating and purifying to obtain a compound of a formula 9;
(7) dissolving the compound shown in the formula 9 in an ethyl acetate solution at 0 ℃, slowly dropwise adding a 2M hydrochloric acid solution dissolved in ethyl acetate, stirring at room temperature for 1 hour, and separating and purifying to obtain a compound shown in the formula 10;
(8) dissolving the compound shown in the formula 10 in a tetrahydrofuran solvent, adding lithium aluminum hydride at 0 ℃, and reacting for a period of time to obtain a compound shown in a formula 11;
(9) dissolving the compound shown in the formula 11 in dichloromethane, adding trifluoroacetic acid at 0 ℃, and reacting at room temperature for 1 hour to obtain a compound shown in the formula 12;
(10) dissolving the compound shown in the formula 12 in an N, N-dimethylformamide solvent at 0 ℃, adding the compound shown in the formula 13, a complex of copper trifluoromethanesulfonate and toluene and sodium carbonate into the mixed solution, refluxing, separating and purifying to obtain a compound shown in the formula 14;
(11) dissolving a compound shown in a formula 14 in N-methylpyrrolidone, adding a compound shown in a formula 15, lithium chloride, [1, 1-bis (diphenylphosphino) ferrocene ] palladium dichloride dichloromethane complex and cesium carbonate, and refluxing at 100 ℃ for 24 hours to obtain a compound shown in a formula 16;
(12) dissolving the compound shown in the formula 16 in a tetrahydrofuran solvent, adding lithium aluminum hydride, refluxing for 8h at 60 ℃, separating and purifying to obtain a compound 17, namely the (-) -psycotriasine.
Preferably, the steps (1) to (12) are all carried out under the protection of nitrogen.
Preferably, the reaction conditions of step (3) are as follows: dissolving zinc powder and cuprous chloride in a 2-methyltetrahydrofuran solution, heating to 85 ℃, refluxing for 30 minutes, removing heat, dropwise adding a compound shown in the formula 5 at room temperature, stirring for 30 minutes, reacting at 50 ℃ for 30 minutes, adding a compound shown in the formula 4 at 0 ℃, reacting for 10 minutes, and separating and purifying to obtain a compound shown in the formula 6.
Preferably, the reaction time of the step (8) is as follows: after 30 minutes at 0 ℃ the reaction mixture was allowed to cool to room temperature for 1 hour, and then warmed to 80 ℃ for 12 hours.
Preferably, the refluxing time of the step (10) is as follows: reflux at 65 ℃ for 24 hours.
Preferably, the preparation method of the compound of formula 15 in step (11) comprises the following steps: dissolving the compound shown in the formula 21 in a methanol solution at 0 ℃ under the protection of nitrogen, then slowly dropwise adding methyl chloroformate, adding potassium carbonate, reacting at 0 ℃ for 30 minutes, moving to room temperature, reacting for 8 hours, and separating and purifying to obtain the compound shown in the formula 15.
Preferably, the compound of formula 21 is prepared by a process comprising: under the protection of nitrogen, the compound of formula 20 is dissolved in tetrahydrofuran solution, then triphenylphosphine and a small amount of water are added into the tetrahydrofuran solution, and after refluxing is carried out for 1.5 hours at 50 ℃, the compound of formula 21 is obtained through separation and purification.
Preferably, the compound of formula 20 is prepared by a process comprising: under the protection of nitrogen, the compound of formula 19 is dissolved in N, N-dimethylformamide solution, then sodium azide is added in batches, and after refluxing for 3 hours at 90 ℃, the compound of formula 20 is obtained through separation and purification.
Preferably, the compound of formula 19 is prepared by a process comprising: under the protection of nitrogen, the compound of formula 18 is dissolved in dichloromethane solution at 0 ℃, then triethylamine and paratoluensulfonyl chloride are added into the dichloromethane solution at 0 ℃, and after stirring for 18 hours at room temperature, the compound of formula 19 is obtained through separation and purification.
Compared with the prior art, the invention has the beneficial effects that:
1. the design of the whole synthesis route is unique, the (-) -Psychotrianine is synthesized in a single selective way, the speed is high, the side reaction is relatively less, and the product yield is high;
2. the conventional chemical reagent is utilized in the route, the raw materials and the reagent are cheap and easy to obtain, and the production cost can be greatly reduced;
3. the synthesis route has simple and reasonable design, simple and convenient operation process, mild reaction conditions in the reaction process, less linear steps and suitability for industrial preparation.
Drawings
FIG. 1 is a reaction scheme of the present invention.
Detailed Description
The present invention will be further described with reference to examples.
Example 1
Synthesis of Compounds of formula 3
Dissolving a compound (3g, 20.48mmol, 1.0eq.) of formula 1 in 20.5ml of a dry N, N-dimethylformamide solution at room temperature under the protection of nitrogen, adding sodium hydride (0.59g, 24.55mmol, 1.2eq.) in portions to the solution to change the solution from red to purple, stirring for 60 minutes, adding a compound (7.27g, 22.5mmol, 1.1eq.) of formula 2 to change the solution from purple to yellow, adding water (40ml) to the mixed system after TLC detection reaction is completed, washing with saturated saline and drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and separating the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether: 1: 15) to obtain a white liquid, namely, the compound (6.94g, 87%) of formula 3.
Example 2
Synthesis of Compound of formula 4
Dissolving a compound (1g, 2.57mmol, 1.0eq.) of formula 3 in 13mL of dichloromethane solution at room temperature under the protection of nitrogen, adding (S) - (-) -tert-butylsulfinamide (0.34g, 2.83mmol, 1.1eq.) and tetraethyl titanate (1.46g, 6.43mmol, 2.5eq.) at room temperature, refluxing at 50 ℃ for 6 hours, adding a saturated sodium bicarbonate solution (10mL) to the system after TLC detection reaction is completed, extracting with dichloromethane (3X 20mL), combining the obtained organic phases, washing with saturated brine and drying over anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, separating and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether ═ 1: 10) to obtain a white liquid, namely the compound (1.27g, 91%) of formula 4.
Example 3
Synthesis of Compounds of formula 6
Dissolving zinc powder (1.37g, 21.1mmol, 10eq.) and cuprous chloride (0.31g, 3.17mmol, 1.5eq.) in 2-methyltetrahydrofuran solution at room temperature under the protection of nitrogen, heating to 85 deg.C and refluxing for 30 min, removing the heated room temperature, dropwise adding compound of formula 5 (0.53g, 3.17mmol, 1.5eq.), stirring at room temperature for 30 min, reacting at 50 deg.C for 30 min, cooling to 0 deg.C, adding compound of formula 4(1.04g, 2.11mmol, 1.0eq.) at 0 deg.C, filtering with diatomaceous earth after TLC reaction is completed, removing excess zinc, extracting the filtrate with ethyl acetate (3 × 20mL), combining the obtained organic phases, washing with saturated brine and drying with sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether column chromatography ═ 1: 3) to obtain white liquid, i.e. the compound of formula 6 (1.13g, 90%).
Example 4
Synthesis of Compounds of formula 7
Dissolving the compound of formula 6 (1.12g, 1.89mmol, 1.0eq.) in 9.5mL dichloromethane solution at 0 ℃ under the protection of nitrogen, adding lithium borohydride (0.16g, 7.56mmol, 4.0eq.) in portions, moving to room temperature until the solution turns red from yellow, adding saturated aqueous solution (12mL) to the mixture system after TLC reaction is completed, extracting with dichloromethane (3 × 20mL), combining the obtained organic phases, washing with saturated brine and drying with sodium sulfate, removing the organic solvent by concentration under reduced pressure, and separating and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether ═ 1: 3) to obtain a white solid, namely the compound of formula 7 (0.84g, 82%).
Example 5
Synthesis of Compounds of formula 8
Dissolving a compound of formula 7 (0.5g, 0.931mmol, 1.0eq.) in 10mL of dichloromethane solution at 0 ℃ under the protection of nitrogen, adding dess-martin oxidant (0.59g, 1.40 mmol, 1.5eq.) in portions, reacting at room temperature, changing the solution from red to brown, after the reaction is completed according to TLC, slowly adding saturated sodium bicarbonate solution (4mL) dropwise to the mixed system at 0 ℃, extracting with dichloromethane (3X 20mL), combining the obtained organic phases, washing with saturated brine and drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and separating and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether ═ 1: 2) to obtain a white solid, namely the compound of formula 8 (0.47g, 95%).
Example 6
Synthesis of Compounds of formula 9
Dissolving a compound of formula 8 (1.3g, 2.42mmol, 1.0eq.) in 12mL of methanol solution at 0 ℃ under the protection of nitrogen, adding methylamine hydrochloride (0.12g, 24.2mmol, 10eq.), triethylamine (2.45g, 24.2mmol, 10eq.) and anhydrous magnesium sulfate (1.17g, 9.68mmol, 4eq.), moving to room temperature for reaction for 12 hours, adding sodium borohydride (0.27g, 7.26mmol, 3eq.) at 0 ℃, adding an aqueous solution (6mL) to the mixed system at 0 ℃ after the TLC reaction is completed, extracting with ethyl acetate (3 × 20mL), combining the obtained organic phases, washing with saturated brine and drying with anhydrous sodium sulfate, removing the organic solvent by concentration under reduced pressure, separating the obtained crude product by flash column chromatography (methanol: dichloromethane ═ 1: 20) to obtain a yellow liquid, i.e. 9.23 g of compound of formula 9, 92%).
Example 7
Synthesis of Compounds of formula 10
The compound of formula 9 (0.21g, 0.38mmol, 1.0eq.) was dissolved in 7mL of ethyl acetate solution at 0 ℃ under nitrogen protection, hydrochloric acid (2.0M,7.6 mL) dissolved in ethyl acetate was slowly added dropwise thereto, and after stirring at room temperature for 1 hour, a saturated sodium bicarbonate solution (10mL) was added to the mixed system at 0 ℃, extracted with ethyl acetate (3 × 20mL), the resulting organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate, the organic solvent was removed by concentration under reduced pressure, and the resulting crude product was separated and purified by flash column chromatography (methanol: dichloromethane ═ 1: 20) to give a yellow liquid, i.e., the compound of formula 10 (0.15g, 90%).
Example 7
Synthesis of Compounds of formula 11
Dissolving a compound of formula 10 (1.09g, 2.44mmol, 1.0eq.) in 12mL of dry tetrahydrofuran solvent at 0 ℃ under the protection of nitrogen, adding lithium aluminum hydride (0.46g, 12.2mmol, 5eq.) at 0 ℃, reacting at 0 ℃ for 30 minutes, then turning to room temperature for 1 hour, subsequently heating to 80 ℃ to continue the reaction, adding an aqueous solution (5mL) to the mixed system at 0 ℃ after the reaction is completed according to TLC detection, extracting with ethyl acetate (3X 20mL), combining the obtained organic phases, washing with saturated saline and drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and separating the obtained crude product by flash column chromatography (methanol: dichloromethane ═ 1: 50) to obtain a yellow liquid, namely, the compound of formula 11 (0.90g, 85%).
Example 8
Synthesis of Compounds of formula 12
Dissolving the compound of formula 11 (0.83g, 1.92mmol, 1.0eq.) in 5mL of dichloromethane at room temperature under the protection of nitrogen, adding trifluoroacetic acid (3.54g, 31.02mmol, 16.2eq.) at 0 ℃ for reaction for 1 hour, adding 4mL of methanol to the reaction system after the reaction is completed according to TLC detection, stirring for ten minutes, concentrating under reduced pressure, adding a saturated sodium bicarbonate solution (20mL) to the mixed system, extracting with dichloromethane (3X 20mL), combining the obtained organic phases, washing with saturated brine and drying with sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and separating and purifying the obtained crude product by flash column chromatography (methanol: dichloromethane ═ 1: 30) to obtain an anhydrous liquid, namely the compound of formula 12 (0.33g, 90%).
Example 9
Synthesis of a compound of formula 14:
dissolving a compound of formula 12 (0.45g, 2.38mmol, 1.0eq.), a complex of copper trifluoromethanesulfonate and toluene (0.62g, 1.19mmol, 0.5eq.), a compound of formula 13 (3.94g, 7.14mmol, 3eq.) and sodium carbonate (0.50g, 4.76mmol, 2eq.) in 12mL of an N, N-dimethylformamide solvent at 0 ℃ under the protection of nitrogen, refluxing at 65 ℃ for 24 hours, adding an aqueous solution (40mL) to the mixed system after the TLC measurement reaction is completed, extracting with ethyl acetate (3 × 10mL), combining the obtained organic phases, washing with saturated brine and drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and separating and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether 1: 2) to obtain a light yellow liquid, namely, a compound of formula 14 (0.43g, 52%).
Example 9
Synthesis of Compounds of formula 15
The compound of formula 18 (0.23g, 1.61mmol, 1.0eq.) was dissolved in dichloromethane (3mL) at 0 ℃ under nitrogen protection, triethylamine (0.33g, 3.22mmol, 2.0eq.) and p-toluenesulfonyl chloride (0.31g, 1.63mmol, 1.01eq.) were added thereto at 0 ℃, stirred at room temperature for 18 hours, after completion of the TLC assay reaction, a saturated aqueous ammonium chloride solution (5mL) was added to the mixed system, extracted with dichloromethane (3 × 10mL), the resulting organic phases were combined, washed with saturated brine and dried over sodium sulfate, and concentrated under reduced pressure to remove the organic solvent, and the resulting crude product 19(0.45g, 94%) was used in the next step without purification.
Dissolving a compound of formula 19 (0.16g, 0.539mmol, 1.0eq.) in N, N-dimethylformamide (1mL) at room temperature under the protection of nitrogen, then adding sodium azide (0.04g, 0.97mmol, 1.8eq.) in portions thereto, refluxing at 90 ℃ for 3 hours, after completion of TLC reaction, adding an aqueous solution (4mL) to the mixed system, extracting with dichloromethane (3 × 5mL), combining the resulting organic phases, washing with saturated brine and drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and separating and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether: 1: 10) to obtain a colorless liquid, i.e., a compound of formula 20 (0.083g, 92%).
Dissolving a compound of formula 20 (0.13g, 0.78mmol, 1.0eq.) in tetrahydrofuran (4mL) at room temperature under the protection of nitrogen, adding triphenylphosphine (0.818g, 3.12mmol, 4.0eq.) and water (0.1mL) thereto, refluxing at 50 ℃ for 1.5 hours, adding an aqueous solution (5mL) to the mixed system after completion of the TLC assay reaction, extracting with ethyl acetate (3 × 10mL), combining the resulting organic phases, washing with saturated brine and drying with sodium sulfate, concentrating under reduced pressure to remove the organic solvent, and purifying the resulting crude product by flash column chromatography (methanol: dichloromethane ═ 1: 20) to obtain an anhydrous liquid, i.e., a compound of formula 21 (0.082g, 74%).
Dissolving the compound of formula 21 (0.22g, 1.55mmol, 1.0eq.) in methanol (8mL) at 0 ℃ under the protection of nitrogen, slowly adding methyl chloroformate (0.176g, 1.86mmol, 1.2eq.) dropwise, adding potassium carbonate (0.45g, 3.255mmol, 2.1eq.) thereto, reacting at 0 ℃ for 30 minutes, moving to room temperature for 8 hours, after completion of the reaction by TLC, adding saturated aqueous ammonium chloride solution (10mL) to the mixed system, extracting with dichloromethane (3 × 10mL), combining the obtained organic phases, washing with saturated brine and drying over anhydrous sodium sulfate, concentrating under reduced pressure to remove the organic solvent, separating and purifying the obtained crude product by flash column chromatography (ethyl acetate: petroleum ether ═ 1: 5) to obtain a light yellow liquid, i.e. the compound of formula 15 (0.25g, 83%).
Example 10
Synthesis of Compounds of formula 16
Dissolving the compound of formula 14 (0.23g, 0.66mmol, 1.0eq.) in 3.5mL of N-methylpyrrolidone solvent at room temperature under the protection of nitrogen, followed by addition of the compound of formula 15 (1.32g, 6.6mmol, 10eq.), lithium chloride (0.03g, 0.66mmol, 1 eq), [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride dichloromethane complex (0.11g, 0.132mmol, 0.2eq.), cesium carbonate (0.43g, 1.32mmol, 2eq.), reflux at 100 ℃ for 24 hours, after completion of TLC measurement reaction, filtration with celite, addition of 132mL of 1.0M hydrochloric acid to the filtrate, addition of ethyl acetate to the filtrate 30mL, washing of the obtained organic phase with saturated sodium bicarbonate, extraction with ethyl acetate (3 × 15mL), combination of the obtained organic phases, washing with saturated sodium sulfate and drying without water, the organic solvent was removed by concentration under reduced pressure, and the obtained crude product was isolated and purified by flash column chromatography (methanol: dichloromethane ═ 1: 15) to obtain a light yellow liquid, i.e., the compound of formula 16 (0.22g, 87%).
Example 11
Synthesis of Compounds of formula 17
Dissolving a compound of formula 16 (100mg, 0.264mmol,1.0eq.) in 1.4mL of tetrahydrofuran solvent at room temperature under the protection of nitrogen, adding lithium aluminum hydride (0.05g,1.32mmol, 5eq.) into the tetrahydrofuran solvent, refluxing at 60 ℃ for 8 hours, adding an aqueous solution (40mL) into the mixed system after TLC reaction is completed, extracting with ethyl acetate (3 × 5mL), combining the obtained organic phases, washing with saturated common salt water and drying with anhydrous sodium sulfate, removing the organic solvent by concentration under reduced pressure, separating and purifying the obtained crude product by flash column chromatography (methanol: dichloromethane ═ 1: 5) to obtain a light yellow liquid, namely the compound of formula 17 (72.4mg, 82%) is the (-) -pseudotriesine.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included therein.
Claims (9)
1. A synthetic method of a natural product (-) -Psychotriasine is characterized by comprising the following steps: the synthesis of the natural product (-) -Psychotriasine comprises the following steps:
(1) dissolving the compound shown in the formula 1 in an N, N-dimethylformamide solvent, adding sodium hydride in batches to enable the solution to become purple, stirring for 1 hour, adding the compound shown in the formula 2 to enable the solution to become yellow, and stirring for 12 hours to obtain a compound shown in the formula 3;
(2) dissolving the compound shown in the formula 3 in dichloromethane, adding (S) - (-) -tert-butyl sulfinamide and tetraethyl titanate, raising the temperature to 50 ℃ to perform condensation reaction, refluxing for 6 hours until the solution turns red, and separating and purifying to obtain the compound shown in the formula 4;
(3) reacting a compound shown in a formula 4 with a compound shown in a formula 5 in a 2-methyltetrahydrofuran solvent environment to obtain a compound shown in a formula 6;
(4) dissolving the compound shown in the formula 6 in dichloromethane at 0 ℃, adding lithium borohydride in batches to perform a reduction reaction, changing the solution from yellow to red, and separating and purifying to obtain a compound shown in the formula 7;
(5) dissolving the compound shown in the formula 7 in dichloromethane at 0 ℃, carrying out oxidation reaction with a dess-martin oxidant at room temperature for 2h, and separating and purifying to obtain a compound shown in the formula 8;
(6) dissolving the compound of the formula 8 in methanol at 0 ℃, adding methylamine hydrochloride, triethylamine and anhydrous magnesium sulfate at room temperature, reacting at room temperature for 12 hours, adding sodium borohydride into the mixture, reacting for 30 minutes, and separating and purifying to obtain a compound of a formula 9;
(7) dissolving the compound shown in the formula 9 in an ethyl acetate solution at 0 ℃, slowly dropwise adding a 2M hydrochloric acid solution dissolved in ethyl acetate, stirring at room temperature for 1 hour, and separating and purifying to obtain a compound shown in the formula 10;
(8) dissolving the compound shown in the formula 10 in a tetrahydrofuran solvent, adding lithium aluminum hydride at 0 ℃, and reacting for a period of time to obtain a compound shown in a formula 11;
(9) dissolving the compound shown in the formula 11 in dichloromethane, adding trifluoroacetic acid at 0 ℃, and reacting at room temperature for 1 hour to obtain a compound shown in the formula 12;
(10) dissolving the compound shown in the formula 12 in an N, N-dimethylformamide solvent at 0 ℃, adding the compound shown in the formula 13, a complex of copper trifluoromethanesulfonate and toluene and sodium carbonate into the mixed solution, refluxing, separating and purifying to obtain a compound shown in the formula 14;
(11) dissolving a compound shown in a formula 14 in N-methylpyrrolidone, adding a compound shown in a formula 15, lithium chloride, [1, 1-bis (diphenylphosphino) ferrocene ] palladium dichloride dichloromethane complex and cesium carbonate, and refluxing at 100 ℃ for 24 hours to obtain a compound shown in a formula 16;
(12) dissolving the compound shown in the formula 16 in a tetrahydrofuran solvent, adding lithium aluminum hydride, refluxing for 8h at 60 ℃, separating and purifying to obtain a compound 17, namely the (-) -psycotriasine.
2. The synthesis of the natural product (-) -psycotriasine according to claim 1, characterized in that: and (3) carrying out the steps (1) to (12) under the protection of nitrogen.
3. The synthesis of the natural product (-) -psycotriasine according to claim 1, characterized in that: the reaction conditions of the step (3) are as follows: dissolving zinc powder and cuprous chloride in a 2-methyltetrahydrofuran solution, heating to 85 ℃, refluxing for 30 minutes, removing heat, dropwise adding a compound shown in the formula 5 at room temperature, stirring for 30 minutes, reacting at 50 ℃ for 30 minutes, adding a compound shown in the formula 4 at 0 ℃, reacting for 10 minutes, and separating and purifying to obtain a compound shown in the formula 6.
4. The synthesis of the natural product (-) -psycotriasine according to claim 1, characterized in that: the reaction time of the step (8) is as follows: after 30 minutes at 0 ℃ the reaction mixture was allowed to cool to room temperature for 1 hour, and then warmed to 80 ℃ for 12 hours.
5. The synthesis of the natural product (-) -psycotriasine according to claim 1, characterized in that: the refluxing time of the step (10) is as follows: reflux at 65 ℃ for 24 hours.
6. The synthesis of the natural product (-) -psycotriasine according to claim 1, characterized in that: the preparation method of the compound of formula 15 in the step (11) comprises the following steps: dissolving the compound shown in the formula 21 in a methanol solution at 0 ℃ under the protection of nitrogen, then slowly dropwise adding methyl chloroformate, adding potassium carbonate, reacting at 0 ℃ for 30 minutes, moving to room temperature, reacting for 8 hours, and separating and purifying to obtain the compound shown in the formula 15.
7. A process for the preparation of a compound of formula 15 according to claim 6, characterized in that: the preparation method of the compound of the formula 21 comprises the following steps: under the protection of nitrogen, the compound of formula 20 is dissolved in tetrahydrofuran solution, then triphenylphosphine and a small amount of water are added into the tetrahydrofuran solution, and after refluxing is carried out for 1.5 hours at 50 ℃, the compound of formula 21 is obtained through separation and purification.
8. A process for the preparation of a compound of formula 21 according to claim 7, characterized in that: the preparation method of the compound of the formula 20 comprises the following steps: under the protection of nitrogen, the compound of formula 19 is dissolved in N, N-dimethylformamide solution, then sodium azide is added in batches, and after refluxing for 3 hours at 90 ℃, the compound of formula 20 is obtained through separation and purification.
9. A process for the preparation of a compound of formula 20 according to claim 8, characterized in that: the preparation method of the compound of the formula 19 comprises the following steps: under the protection of nitrogen, the compound of formula 18 is dissolved in dichloromethane solution at 0 ℃, then triethylamine and paratoluensulfonyl chloride are added into the dichloromethane solution at 0 ℃, and after stirring for 18 hours at room temperature, the compound of formula 19 is obtained through separation and purification.
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