Total synthesis method of Ervitsine

Abstract

The invention provides a total synthesis method of Ervitsine. According to the total synthesis method of Ervitsine, halogenated furan is used as a raw material, and an organic total synthesis method is used for preparing indole alkaloid Ervitsine. The total synthesis method of the indole alkaloid Ervitsine, provided by the invention, has the advantages of cheap and easily available raw materials, mild reaction conditions, short steps, high total yield and low production cost, and has a good industrial production prospect.

Description

Technical Field

[0001] The invention relates to a total synthesis method of Ervitsine, and belongs to the technical field of organic chemical synthesis. Background Art

[0002] The natural product Ervitsine is an indole alkaloid natural product isolated from the oleander plant Pandaca boiteaui by Professor Husson and his collaborators in 1977. Its structural formula is shown below: Ervitsine (1).

[0003]

[0004] Indole alkaloids are the largest branch of the alkaloid family. The indole structure connected to the seven-membered ring is called cyclohepta [b] indoles. Compounds containing this structure show a wide range of biological activities. The natural product Ervitsine is one of them. Another alkaloid with a very similar structure, Methuenine, is an anticholinergic agent. In addition, unlike other cyclohepta [b] indole alkaloids, Ervitsine has unique C5-C7 and C6-C16 bonds in its structure, which has very important synthetic value. Due to the limitation of natural sources, the amount of this natural product isolated from nature is very small, and it is difficult to conduct more in-depth biological activity research. Therefore, it is crucial to invent an efficient synthesis method for further activity research of natural products.

[0005] The Bosch research group completed the biomimetic synthesis of Ervitsine in 1993. They used 2-acetylindole as the starting material, reacted with pyridine compounds under the action of a strong base, and the intermediate then attacked Eschenmoser salt, and finally obtained a tetracyclic compound with a yield of 15%. It was then oxidized with m-chloroperbenzoic acid to obtain nitrogen oxides, and the obtained nitrogen oxides under toluene reflux conditions underwent Cope elimination to form a terminal double bond, and compound VI was obtained with a yield of 45%, and then the natural product Ervitsine was finally obtained with a yield of 65%. Its synthetic route is as follows.

[0006]

[0007] However, this synthetic technology route has a low yield, and it is difficult to achieve diverse synthesis of the molecule, making subsequent research on the biological activity and drugability of the natural product difficult. Summary of the invention

[0008] Based on the above problems, the present invention provides a short method for synthesizing the natural product Ervitsine, and its structure can be easily modified, which can provide sufficient material basis for future biological activity research and screening of lead compounds in new drug development. It is believed that it will contribute to major human diseases such as anti-inflammatory and anti-tumor.

[0009] According to the first aspect of the present application, an intermediate compound for synthesizing Ervitsine is provided, wherein the intermediate compound includes compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 14, compound 15, compound 16, compound 17, compound 18, compound 19, and compound 20, corresponding to the structures shown below: , , , , , , , , , , , , , , .

[0010] According to the second aspect of the present application, a method for preparing the intermediate compound described above is provided, and the method for preparing compound 4 comprises: A mixture containing halogenated furan, solvent 1, lithium diisopropylamide, benzyl chloromethyl ether, n-butyl lithium, and compound 3 is reacted with 1 to obtain the compound 4; The compound 3 has the structure shown below: .

[0011] Optionally, the halogenated furan is 3-bromofuran.

[0012] Optionally, the solvent 1 is selected from at least one of diethyl ether and tetrahydrofuran.

[0013] Optionally, the molar ratio of the halogenated furan, lithium diisopropylamide, benzyl chloromethyl ether and n-butyl lithium is: 1: (1.1-1.3): (1.1-1.2): (1.2-1.4).

[0014] Optionally, the molar ratio of the halogenated furan to the compound 3 is 1:1.3~1.5.

[0015] Optionally, the molar volume ratio of the halogenated furan to the solvent 1 is 0.2-0.3:1 mol / L.

[0016] Optionally, the temperature of reaction 1 is -40 to -60°C, and the time of reaction 1 is 2 to 5 hours.

[0017] According to the third aspect of the present application, a method for preparing the intermediate compound described above is provided, and the method for preparing compound 6 comprises: A mixture containing compound 4, compound 5, solvent 2, and potassium carbonate is reacted 2 to obtain the compound 6; The compound 5 has the structure shown below: .

[0018] Optionally, the solvent 2 is acetone.

[0019] Optionally, the molar ratio of the compound 4 to the compound 5 is 1:1.1~1.2.

[0020] Optionally, the molar ratio of the compound 4 to the potassium carbonate is 1:2.5~3.0.

[0021] Optionally, the molar volume ratio of the compound 4 to the solvent 2 is 0.1~0.2:1 mol / L.

[0022] Optionally, the temperature of reaction 2 is 50-55° C., and the time of reaction 2 is 10-12 h.

[0023] Optionally, the preparation method of the compound 7 comprises: reacting a mixture containing compound 6, solvent 3 and sodium borohydride by reaction 3 to obtain the compound 7.

[0024] Optionally, the solvent 3 is a mixed solvent, the mixed solvent is tetrahydrofuran and water, and the volume ratio of tetrahydrofuran to water is 4:1.

[0025] Optionally, the molar volume ratio of the compound 6 to the solvent 3 is 0.1~0.2:1 mol / L.

[0026] Optionally, the molar ratio of the compound 6 to the sodium borohydride is 1:1.0~1.5.

[0027] Optionally, the temperature of reaction 3 is 0-25° C., and the time of reaction 3 is 0.5-2 h.

[0028] Optionally, the preparation method of the compound 8 comprises: reacting a mixture containing compound 7, solvent 4, 2.6-lutidine, triisopropylsilyl trifluoromethanesulfonate, and potassium tert-butoxide by reaction 4 to obtain the compound 8.

[0029] Optionally, the solvent 4 is tetrahydrofuran.

[0030] Optionally, the molar ratio of compound 7, 2,6-dimethylpyridine, triisopropylsilyl trifluoromethanesulfonate and potassium tert-butoxide is: 1: (2.5-3): (1.1-1.2): (1.3-1.5).

[0031] Optionally, the molar volume ratio of the compound 7 to the solvent 4 is 0.07~0.2:1 mol / L.

[0032] Optionally, the temperature of reaction 4 is 0-25° C., and the time of reaction 4 is 0.5-3 h.

[0033] According to the fourth aspect of the present application, a method for preparing the intermediate compound described above is provided, and the method for preparing compound 9 comprises: A mixture containing compound 8, solvent 5 and peroxyacetone is reacted 5 to obtain the compound 9.

[0034] Optionally, the molar ratio of the compound 8 to the acetone peroxide is 1:2.5-3.0.

[0035] Optionally, the molar volume ratio of the compound 8 to the solvent 5 is 0.001~0.05:1 mol / L.

[0036] Optionally, the solvent 5 is dichloromethane.

[0037] Optionally, the temperature of reaction 5 is -78 to -40°C, and the time of reaction 5 is 0.2 to 0.5h.

[0038] Optionally, the preparation method of the compound 10 comprises: reacting a mixture containing compound 9, solvent 6, palladium carbon, triphenylphosphine, imidazole and iodine under a hydrogen atmosphere to obtain the compound 10.

[0039] Optionally, the molar ratio of compound 9, palladium on carbon, triphenylphosphine, imidazole and iodine is: 1: (0.1-0.15): (2.5-3): (2.5-3): (1.5-2).

[0040] Optionally, the solvent 6 is toluene.

[0041] Optionally, the molar volume ratio of the compound 9 to the solvent 6 is 0.03~0.05:1 mol / L.

[0042] Optionally, the temperature of reaction 6 is 20-30° C., and the reaction time is 1-2 h.

[0043] Optionally, the preparation method of the compound 11 comprises: subjecting a mixture containing the compound 10, the solvent 7 and zinc powder to a reaction 7 to obtain the compound 11.

[0044] Optionally, the solvent 7 includes isopropanol, tert-butanol and water, and the ratio of isopropanol:tert-butanol:water=10 ml:10 ml:0.2 ml.

[0045] Optionally, the molar ratio of the compound 10 to the zinc powder is 1:10.0-12.0.

[0046] Optionally, the molar volume ratio of the compound 10 to the solvent 7 is 0.01-0.02:1 mol / L.

[0047] Optionally, the temperature of reaction 7 is 80-95° C., and the time of reaction 7 is 2-5 h.

[0048] According to the fifth aspect of the present application, a method for preparing the intermediate compound described above is provided, wherein the method for preparing compound 12 comprises: A mixture containing compound 11, solvent 8, 2,6-lutidine, tert-butyldimethylsilyl trifluoromethanesulfonate, p-toluenesulfonyl hydrazide and acetic acid is reacted with 8 to obtain the compound 12.

[0049] Optionally, the solvent 8 is 1.2-dichloroethane.

[0050] Optionally, the molar ratio of the compound 11, 2,6-dimethylpyridine, tert-butyldimethylsilyl trifluoromethanesulfonate, and p-toluenesulfonyl hydrazide is: 1: (1.6-2.0): (1.5-1.8): (1.5-2.0).

[0051] Optionally, the molar volume ratio of the compound 11 to the solvent 8 is 0.06~0.1:1 mol / L.

[0052] Optionally, the molar volume ratio of the compound 11 to the acetic acid is 20~35:1 mol / L.

[0053] Optionally, the temperature of the reaction 8 is 0-50° C., and the time of the reaction 8 is 5 min-12 h.

[0054] Optionally, the preparation method of the compound 14 comprises: reacting a mixture containing the compound 12, tetrakistriphenylphosphine palladium, o-iodoaniline, potassium carbonate and toluene by reaction 9 to obtain the compound 14.

[0055] Optionally, the molar ratio of the compound 12, tetrakistriphenylphosphine palladium, o-iodoaniline and potassium carbonate is: 1: (0.1-0.12): (3.3-3.5): (4.0-5.0).

[0056] Optionally, the molar volume ratio of the compound 12 to the toluene is 0.05~0.1:1 mol / L.

[0057] Optionally, the temperature of the reaction 9 is 110-120° C., and the time of the reaction 8 is 10-18 h.

[0058] According to the sixth aspect of the present application, a method for preparing the intermediate compound is provided, and the method for preparing compound 15 comprises: A mixture containing compound 14, solvent 9, iodobenzene trifluoroacetate and tetrabutylammonium fluoride is reacted 10 to obtain the compound 15.

[0059] Optionally, the solvent 9 is tetrahydrofuran.

[0060] Optionally, the molar ratio of compound 14, iodobenzene trifluoroacetate and tetrabutylammonium fluoride is: 1: (1.3-1.5): (4.5-5.5).

[0061] Optionally, the molar volume ratio of the compound 14 to the solvent 9 is 0.01-0.05:1 mol / L.

[0062] Optionally, the temperature of the reaction 10 is -20 to 0°C, and the time of the reaction 10 is 10 min to 3 h.

[0063] Optionally, the preparation method of the compound 16 comprises: reacting a mixture containing compound 15, solvent 10, lithium naphthalene, triethylamine, and di-tert-butyl dicarbonate with reaction 11 to obtain the compound 16.

[0064] Optionally, the molar ratio of compound 15, lithium naphthalene, triethylamine and di-tert-butyl dicarbonate is: 1: (5.0~10.0): (2.5~3.0): (2.5~3.0).

[0065] Optionally, the molar volume ratio of the compound 15 to the solvent 10 is 0.03~0.1:1 mol / L.

[0066] Optionally, the solvent 10 is selected from at least one of ethylene glycol dimethyl ether and tetrahydrofuran.

[0067] Optionally, the temperature of the reaction 11 is -78 to -40°C, and the time of the reaction 11 is 10 min to 0.5 h.

[0068] According to the seventh aspect of the present application, a method for preparing the intermediate compound described above is provided, wherein the method for preparing compound 19 comprises the following steps: S1: reacting a mixture containing compound 16, solvent 11, and pyridinium dichromate with 12 to obtain a product containing compound 17; S2: Dissolve the product containing compound 17 and add it to a mixture containing compound 18, solvent 12, and potassium bis(trimethylsilyl)amide to react 13 to obtain compound 19.

[0069] Optionally, in step S1, the molar ratio of the compound 16 to the pyridinium dichromate is 1:5.0-6.0.

[0070] Optionally, in step S1, the molar volume ratio of the compound 16 to the solvent 11 is 0.006-0.01:1 mol / L.

[0071] Optionally, in step S1, the solvent 11 is dichloromethane.

[0072] Optionally, in step S1, the temperature of reaction 12 is 0-25° C., and the time of reaction 12 is 20 min-2 h.

[0073] Optionally, in step S2, the molar ratio of the compound 18 to the potassium bis(trimethylsilyl)amide is 1:0.8-1.0.

[0074] Optionally, in step S2, the molar volume ratio of the compound 18 to the solvent 12 is 0.05-0.1:1 mol / L.

[0075] Optionally, in step S2, the solvent 12 is tetrahydrofuran.

[0076] Optionally, in step S2, the temperature of reaction 13 is -78~25°C, and the time of reaction 13 is 1h~3h.

[0077] According to an eighth aspect of the present application, a method for synthesizing Ervitsine is provided, wherein the method for synthesizing Ervitsine comprises the following steps: Step a: reacting a mixture containing compound 19, solvent 13 and diisobutylaluminum hydride with 14 to obtain a product containing compound 20; Step b: After dissolving the product containing compound 20, tetrabutylammonium fluoride and manganese dioxide are added, and the reaction is carried out to obtain the Ervitsine; The compound 19 is consistent with the compound 19 described above; The compound 19 is prepared by the preparation method of the compound 19 described above.

[0078] Optionally, in the step a, the molar ratio of the compound 19 to the diisobutylaluminum hydride is 1:4.0~5.0.

[0079] Optionally, in the step a, the molar volume ratio of the compound 19 to the solvent 13 is 0.001-0.02:1 mol / L.

[0080] Optionally, in step a, the solvent 13 is tetrahydrofuran.

[0081] Optionally, in step a, the temperature of reaction 14 is 0-50° C., and the time of reaction 14 is 0.5 h-1 h.

[0082] Optionally, in the step b, the molar ratio of the compound 19 to the tetrabutylammonium fluoride is 1:1.2-1.5.

[0083] Optionally, in the step b, the molar ratio of the compound 19 to the manganese dioxide is 1:10.0-12.0.

[0084] Optionally, in the step b, the temperature of the reaction 15 is 20-30° C., and the time of the reaction 15 is 0.5 h-1 h.

[0085] According to the ninth aspect of the present application, a total synthesis method for synthesizing Ervitsine is provided, and the synthesis route of the total synthesis method of Ervitsine is as follows: ; Among them, compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 14, compound 15, compound 16, compound 17, compound 18, compound 19, and compound 20 in the synthetic route are consistent with compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 14, compound 15, compound 16, compound 17, compound 18, compound 19, and compound 20 described above.

[0086] The beneficial effects of this application include: The present invention provides a short synthesis method of the natural product Ervitsine, which uses an organic total synthesis method to obtain the indole alkaloid Ervitsine with high efficiency, with a yield of more than 60%, and is easy to modify its structure, which can provide sufficient material basis for future biological activity research and screening of lead compounds in new drug development, and is believed to contribute to major human diseases such as anti-inflammatory and anti-tumor. The synthesis method of the present invention has cheap and readily available raw materials, mild reaction conditions, short steps, high total yield, low production cost, and good prospects for industrial production. DETAILED DESCRIPTION

[0087] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0088] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0089] Example 1 Synthesis of compound 4

[0090] Compound 2 (30 g, 211 mmol, 1.0 equiv.) was dissolved in diethyl ether (800 mL), and lithium diisopropylamide (2.0 M tetrahydrofuran / n-heptane / ethylbenzene solution, 126 mL, 253.2 mmol, 1.2 equiv.) was slowly added at -78 ºC, and stirred at this temperature for one hour. Then, benzyl chloromethyl ether (34.1 mL, 232 mmol, 1.1 equiv.) was added at this temperature, and the mixture was heated to room temperature and stirred for 1 hour. Then the temperature was lowered to -40 ºC, and n-butyl lithium (2.5M n-hexane solution, 118ml, 295 mmol, 1.4 equiv.) was slowly added. After stirring at this temperature for one hour, compound 3 (43.4g, 316.5mmol, 1.5 equiv) was slowly added. After reacting at this temperature for two hours, saturated ammonium chloride solution was added to quench, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the organic phase was concentrated to obtain a crude product by spin drying. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 10:1 → 5:1) to obtain a light yellow oil product 4 (37.8 g, yield 68%).

[0091] R f = 0.6 (petroleum ether / ethyl acetate = 3 / 1); IR (film) λ max2933, 2862, 1697, 1558, 1087, 1066, 740, 698 cm -1 ; 1 H NMR (600 MHz, CDCl3) δ 7.43 (d, J = 2.0 Hz, 1H), 7.34 (d, J = 4.4Hz, 4H), 7.29 (ddd, J = 8.7, 5.0, 3.8 Hz, 1H), 6.70 (d, J = 2.0 Hz, 1H), 4.84(s, 2H), 4.60(s, 2H), 4.45(s, 2H); 13 C NMR (150 MHz, CDCl3) δ 187.0, 158.1, 142.8, 137.5, 128.6, 128.1,128.1, 120.8, 109.9, 73.3, 63.4, 47.5; HRMS (ESI) calculated molecular weight C 14 H 13 ClO3 [M+Na] + : 287.0445; Measured molecular weight: 287.0442.

[0092] Example 2 Synthesis of compound 6

[0093] Compound 4 (23 g, 87 mmol, 1.0 equiv) and compound 5 (19.9 g, 95.7 mmol, 1.1 equiv) were dissolved in 800 ml of acetone, and then anhydrous potassium carbonate (36 g, 261 mmol, 3.0 equiv) was added to the system, and then the system was heated to 50 °C and continued overnight. After cooling to room temperature, the mixed solution was filtered through diatomaceous earth and concentrated. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 10:1 → 4:1) to obtain brown oily product 6 (30.4 g, yield 80%).

[0094] R f = 0.45 (petroleum ether / ethyl acetate = 3 / 1); IR (film) λ max 3284, 2924, 1691, 1348, 1161, 902, 659 cm -1 ; 1 H NMR (600 MHz, CDCl3) δ 7.77 – 7.72 (m, 2H), 7.41 (d, J = 2.0 Hz,1H), 7.33 (d, J = 4.4 Hz, 4H), 7.31 – 7.27 (m, 3H), 6.77 (d, J = 2.0 Hz, 1H), 4.81 (s, 2H), 4.58 (s, 2H), 4.53 (s, 2H), 4.24 (d, J = 2.5 Hz, 2H), 2.42 (s, 3H), 2.08 (t, J = 2.5 Hz, 1H); 13 C NMR (150 MHz, CDCl3) δ 189.4, 157.7, 144.0, 142.7, 137.6, 136.1,129.8, 128.6, 128.1, 128.0, 127.8, 121.1, 109.6, 76.6, 74.6, 73.2, 63.5,53.2, 37.5, 21.7; HRMS (ESI) calculated molecular weight C 24 H 23 NO5S [M+Na] + : 460.1189; Measured molecular weight: 460.1185.

[0095] Example 3 Synthesis of compound 7

[0096] Compound 6 (5 g, 11.4 mmol, 1.0 equiv.) was dissolved in 100 ml of a mixed solvent (tetrahydrofuran / water = 4:1) and cooled to 0 °C, and then sodium borohydride (431 mg, 11.4 mmol, 1.0 equiv) was added in batches. After the reaction was completed, it was quenched with a saturated ammonium chloride solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and dried to obtain a crude product by concentrating the organic phase. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 8:1 → 3:1) to obtain a light yellow oily product 4 (4.3 g, yield 86%).

[0097] R f = 0.3 (petroleum ether / ethyl acetate = 3 / 1); IR (film) λ max3516, 3290, 2924, 1330, 1159, 813, 661 cm -1 ; 1 H NMR (600 MHz, CDCl3) δ 7.73 – 7.69 (m, 2H), 7.37 – 7.29 (m, 5H), 7.29 (ddt, J = 8.5, 5.4, 2.8 Hz, 1H), 7.24 (d, J = 8.1 Hz, 2H), 6.44 (d, J =1.9 Hz, 1H), 5.01 (dd, J = 8.8, 3.7 Hz, 1H), 4.56 (t, J = 3.0 Hz, 4H), 4.23(dd, J = 18.4, 2.5 Hz, 1H), 4.11 (dd, J = 18.4, 2.5 Hz, 1H), 3.43 (dd, J =14.6, 8.8 Hz, 1H), 3.30 (dd, J = 14.6, 3.7 Hz, 1H), 2.91 (s, 1H), 2.40 (s,3H), 1.99 (t, J = 2.5 Hz, 1H); 13 C NMR (150 MHz, CDCl3) δ 148.4, 144.0, 142.5, 137.8, 135.6, 129.7,128.6, 128.1, 128.0, 127.9, 124.0, 109.6, 77.0, 74.1, 72.6, 65.9, 62.9, 53.4,38.7, 21.7; HRMS (ESI) calculated molecular weight C 24 H 25 NO5S [M+Na] + : 462.1346; Measured molecular weight: 462.1341.

[0098] Example 4 Synthesis of compound 8

[0099] Compound 7 (6.8 g, 15 mmol, 1.0 equiv.) was dissolved in 200 ml tetrahydrofuran and cooled to 0°C, and then 2.6-lutidine (5.2 ml, 45 mmol, 3.0 equiv.) and triisopropylsilyl trifluoromethanesulfonate (4.4 ml, 16.5 mmol, 1.1 equiv.) were added in sequence. The reaction was carried out at this temperature for 2 hours, and then potassium tert-butoxide (1.0 M tetrahydrofuran solution, 22.5 ml, 22.5 mmol, 1.5 equiv.) was added to the system. After reacting at this temperature for 30 minutes, the system was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 20:1 → 10:1) to obtain a yellow oily product 8 (6.7 g, yield 75%).

[0100] R f = 0.5 (petroleum ether / ethyl acetate = 10 / 1); IR (film) λ max 2943, 2866, 1346, 1163, 1093, 927, 665 cm -1 ; 1 H NMR (600 MHz, CDCl3) δ 7.64 – 7.60 (m, 2H), 7.40 – 7.36 (m, 2H), 7.36 – 7.31 (m, 3H), 7.31 – 7.27 (m, 1H), 7.24 (d, J = 8.1 Hz, 2H), 6.68 (t,J = 6.2 Hz, 1H), 6.41 (d, J = 1.9 Hz, 1H), 5.21 – 5.12 (m, 3H), 4.60 – 4.55(m, 3H), 4.46 (d, J = 12.5 Hz, 1H), 3.33 (dd, J = 13.9, 6.8 Hz, 1H), 3.06(dd, J = 13.9, 7.1 Hz, 1H), 2.40 (s, 3H), 1.13 – 0.95 (m, 21H); 13C NMR (150 MHz, CDCl3) δ 201.4, 147.8, 143.8, 142.2, 138.3, 134.9,129.8, 128.5, 128.0, 127.7, 127.4, 125.2, 110.0, 101.3, 88.4, 72.7, 66.1,62.7, 53.2, 21.7, 18.1, 18.0, 12.4; HRMS (ESI) calculated molecular weight C 33 H 45 NO5SSi [M+H] + : 596.2860; Measured molecular weight: 596.2857.

[0101] Example 5 Synthesis of compound 9

[0102] Compound 8 (290 mg, 0.48 mmol, 1.0 equiv.) was dissolved in 50 ml of dichloromethane and cooled to -78 °C, then peroxyacetone (0.085 M acetone solution, 10 ml, 0.85 mmol, 2.5 equiv.) was added, and the mixture was reacted for 10 minutes and filtered with a sand core funnel. The filtrate was dried and purified by silica gel column chromatography (petroleum ether / ethyl acetate 10:1 → 5:1) to obtain a light yellow oily product 9 (210 mg, yield 70%).

[0103] R f = 0.5 (petroleum ether / ethyl acetate = 5 / 1); IR (film) λ max 2954, 2910, 2850, 1653, 1558, 1458 cm -1 ; 1H NMR (600 MHz, CDCl3) δ 7.75 – 7.70 (m, 2H), 7.42 – 7.38 (m, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.29 (dd, J = 7.7, 4.9 Hz, 3H), 5.99 (t, J = 1.3Hz, 1H), 5.10 (dd, J = 4.5, 1.5 Hz, 1H), 4.71 (d, J = 11.2 Hz, 2H), 4.62 (d,J = 11.9 Hz, 1H), 4.58 (ddt, J = 9.3, 6.4, 1.6 Hz, 1H), 3.94 (s, 2H), 3.93 –3.86 (m, 1H), 2.71 (dd, J = 16.5, 4.5 Hz, 1H), 2.42 (s, 3H), 2.30 (d, J =16.5 Hz, 1H), 2.15 (dd, J = 11.8, 9.0 Hz, 1H), 1.12 – 0.92 (m, 21H); 13 C NMR (150 MHz, CDCl3) δ 202.8, 147.3, 143.6, 137.8, 137.1, 129.5,128.5, 128.2, 127.8, 127.7, 125.9, 88.1, 77.4, 74.2, 68.7, 67.2, 65.9, 53.3,46.6, 21.7, 18.0, 12.1; HRMS (ESI) calculated molecular weight C 33 H 45 NO6SSi [M+Na] + : 634.2629; Measured molecular weight: 634.2625.

[0104] Example 6 Synthesis of compound 10

[0105] Compound 9 (210 mg, 0.34 mmol, 1.0 equiv) was dissolved in 10 ml of toluene, and then palladium carbon (10% palladium carbon, 36 mg, 0.034 mmol, 0.1 equiv.) was added. A hydrogen balloon was then inserted and the hydrogen was replaced three times. After reacting at room temperature for 12 hours, the hydrogen balloon was removed, and triphenylphosphine (244 mg, 0.93 mmol, 3.0 equiv.), imidazole (63 mg, 0.93 mmol, 3.0 equiv.), and iodine (158 mg, 0.62 mmol, 2.0 equiv.) were added to the system in sequence. Argon was introduced into the system and the temperature was raised to 80 °C. After reacting for 1 hour, a saturated sodium thiosulfate solution was added to quench the reaction. The reaction mixture was filtered through diatomaceous earth and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 10:1 → 5:1) to give a white solid product 10 (161 mg, yield 75%).

[0106] R f = 0.45 (petroleum ether / ethyl acetate = 5 / 1); IR (film) λ max 2943, 2866, 1728, 1342, 1157 cm -1 ; 1 H NMR (600 MHz, CDCl3) δ 7.74 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.2Hz, 2H), 4.69 – 4.64 (m, 1H), 4.43 (d, J = 1.6 Hz, 1H), 4.06 (dt, J = 10.8,6.0 Hz, 1H), 3.72 (d, J = 11.4 Hz, 1H), 3.67 (d, J = 11.4 Hz, 1H), 3.52 (ddd,J = 13.4, 6.1, 1.5 Hz, 1H), 2.87 – 2.80 (m, 1H), 2.79 – 2.72 (m, 1H), 2.54 –2.45 (m, 1H), 2.43 (s, 3H), 2.34 (dddd, J = 14.4, 11.7, 8.5, 1.5 Hz, 1H), 1.64 – 1.56 (m, 1H), 1.09 – 0.99 (m, 21H); 13C NMR (150 MHz, CDCl3) δ 203.7, 143.7, 136.9, 129.6, 127.7, 81.4,71.8, 65.7, 63.5, 49.7, 49.6, 43.2, 30.4, 21.7, 18.0, 18.0, 12.2, 10.5; HRMS (ESI) calculated molecular weight C 26 H 40 INO5SSi [M+H] + : 634.1514; Measured molecular weight: 634.1511.

[0107] Example 7 Synthesis of compound 11

[0108] Compound 10 (161 mg, 0.25 mmol, 1.0 equiv.) was dissolved in a mixed solvent (isopropanol: tert-butanol: water = 10 ml: 10 ml: 0.2 ml), and the system was heated to 90 °C. After the substrate was completely dissolved, activated zinc powder (160 mg, 2.5 mmol, 10.0 equiv.) was added to the system. After reacting for 2 hours, the mixture was cooled to room temperature, filtered and concentrated with celite, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 8:1 → 3:1) to obtain a colorless oily product 11 (80 mg, yield 63%).

[0109] R f = 0.3 (petroleum ether / ethyl acetate=3 / 1); IR (film) λ max 2943, 2866, 1718, 1342, 1159, 1118, 956, 883 cm -1 ; 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0Hz, 2H), 5.24 (d, J = 5.6 Hz, 2H), 4.65 (s, 1H), 4.31 (dt, J = 9.3, 4.7 Hz,1H), 3.98 (dt, J = 8.2, 6.1 Hz, 1H), 3.29 (dd, J = 13.7, 5.7 Hz, 1H), 3.02(q, J = 6.2 Hz, 1H), 2.94 (dd, J = 13.3, 8.7 Hz, 1H), 2.90 – 2.68 (m, 2H),2.46 (t, J = 4.1 Hz, 1H), 2.42 (s, 3H), 1.80 (s, 1H), 1.74 (ddd, J = 15.0,9.2, 6.7 Hz, 1H), 1.03 (s, 21H); 13 C NMR (100 MHz, CDCl3) δ 205.6, 143.9, 141.7, 135.8, 129.7, 127.9,118.0, 69.0, 67.9, 66.3, 50.7, 47.4, 44.0, 36.8, 21.7, 18.1, 18.1, 12.2; HRMS (ESI) calculated molecular weight C 26 H 41 NO5SSi [M+H] + : 508.2547; Measured molecular weight: 508.2543.

[0110] Example 8 Synthesis of compound 12

[0111] Compound 11 (630 mg, 1.24 mmol, 1.0 equiv.) was dissolved in 20 ml of 1.2-dichloroethane and the temperature was lowered to 0 °C. Then, 2.6-lutidine (0.23 ml, 1.98 mmol, 1.6 equiv.) and tert-butyldimethylsilyl trifluoromethanesulfonate (0.45 ml, 1.86 mmol, 1.5 equiv.) were added to the system in sequence. After reacting at this temperature for 5 minutes, p-toluenesulfonyl hydrazide (460 mg, 2.48 mmol, 2.0 equiv.) and 0.04 ml of acetic acid were added to the system and the temperature was raised to 50 °C. After reacting overnight, the system was cooled to room temperature and quenched by adding saturated ammonium chloride solution. The product was extracted with dichloromethane, and the organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 10:1→5:1) to obtain a yellow oily product 12. (812 mg, 83% yield).

[0112] R f = 0.5 (petroleum ether / ethyl acetate=5 / 1); IR (film) λ max 3219, 2947, 2866, 1558, 1340, 1091, 1047, 837 cm -1 ; 1H NMR (600 MHz, CD2Cl2) δ 7.9 – 7.8 (m, 2H), 7.7 – 7.6 (m, 2H), 7.4(s, 1H), 7.3 (dd, J = 13.2, 8.1 Hz, 4H), 5.0 (dd, J = 7.8, 1.3 Hz, 2H), 5.0(s, 1H), 4.0 (tt, J = 7.9, 3.9 Hz, 1H), 3.7 (dt, J = 9.7, 5.8 Hz, 1H), 3.3(dd, J = 13.8, 5.7 Hz, 1H), 2.8 (dt, J = 7.3, 5.2 Hz, 1H), 2.6 (dd, J = 13.9,9.7 Hz, 1H), 2.4 (s, 3H), 2.4 (s, 3H), 2.4 (dd, J = 14.9, 4.5 Hz, 1H), 2.3(dd, J = 14.9, 8.2 Hz, 1H), 2.0 (dt, J = 14.7, 4.0 Hz, 1H), 1.5 (dd, J =14.8, 7.6 Hz, 1H), 1.0 (q, J = 3.3, 2.7 Hz, 21H), 0.8 (s, 9H), 0.0 (s, 3H), -0.0 (s, 3H); 13 C NMR (150 MHz, CD2Cl2) δ 155.5, 144.8, 144.0, 142.7, 137.1, 135.6, 130.0, 130.0, 128.6, 128.0, 117.0, 69.4, 67.7, 63.5, 46.0, 44.4, 36.3, 35.8,25.8, 21.7, 21.6, 18.1, 18.1, 12.5, -4.7, -4.7; HRMS (ESI) calculated molecular weight C 39 H 63 N3O6S2Si2 [M+H] + : 790.3770; Measured molecular weight: 790.3760.

[0113] Example 9 Synthesis of compound 14

[0114] Compound 12 (817 mg, 1.04 mmol, 1.0 equiv.), tetrakistriphenylphosphine palladium (115 mg, 0.1 mmol, 0.1 equiv.), o-iodoaniline 13 (800 mg, 4.16 mmol, 3.5 equiv.), and anhydrous potassium carbonate (575 mg, 4.16 mmol, 4.0 equiv.) were added to the flask in sequence. After evacuating the argon gas, 20 ml of toluene was added, and then the system was heated to 110 °C and stirred overnight. After the reaction was completed, the temperature was cooled to room temperature, 20 ml of ethyl acetate was added to dilute, and then filtered through diatomaceous earth. The concentrated crude product was purified by column chromatography (petroleum ether / ethyl acetate 15:1 → 10:1) to obtain a yellow oily product 15 (565.0 mg, yield 78%).

[0115] R f = 0.65 (petroleum ether / ethyl acetate = 5 / 1); IR (film) λ max 2947, 2866, 1558, 1338, 1161, 1066, 837 cm -1 ; 1 H NMR (600 MHz, CD2Cl2) δ 7.4 – 7.4 (m, 2H), 7.1 (d, J = 8.0 Hz, 2H), 7.1 (td, J = 7.6, 1.6 Hz, 1H), 6.9 (d, J = 7.8 Hz, 1H), 6.7 – 6.6 (m, 2H),5.8 – 5.8 (m, 1H), 5.2 (s, 1H), 5.1 (d, J = 1.5 Hz, 1H), 4.9 (d, J = 1.5 Hz,1H), 4.9 (ddd, J = 9.9, 5.4, 2.9 Hz, 1H), 3.8 (dt, J = 11.7, 6.0 Hz, 3H), 3.6(dd, J = 14.5, 5.9 Hz, 1H), 3.1 (dd, J = 14.4, 11.3 Hz, 1H), 2.5 (dt, J =13.6, 5.1 Hz, 1H), 2.4 (s, 3H), 1.8 (ddd, J = 14.1, 9.9, 4.6 Hz, 1H), 1.1 –0.9 (m, 21H), 0.9 (s, 9H), 0.0 (d, J = 5.7 Hz, 6H); 13C NMR (150 MHz, CD2Cl2) δ 146.4, 143.8, 143.6, 141.4, 138.0, 137.8,130.4, 130.0, 129.7, 128.7, 127.7, 118.6, 115.6, 112.6, 70.6, 69.2, 45.4,45.4, 38.0, 25.9, 21.6, 18.3, 18.2, 18.2, 12.5, -4.6, -4.6; HRMS (ESI) calculated molecular weight C 38 H 60 N2O4SSi2 [M+H] + : 697.3885; Measured molecular weight: 697.3884.

[0116] Example 10 Synthesis of compound 15

[0117] Compound 14 (41 mg, 0.059 mmol, 1.0 equiv.) was dissolved in 5 ml tetrahydrofuran and cooled to 0 °C, then iodobenzene trifluoroacetate (40 mg, 0.088 mmol, 1.5 equiv.) was added, and after reacting for 10 minutes, the temperature was lowered to -20 °C, and tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 0.29 ml, 0.29 mmol, 5.0 equiv.) was added to the system. After reacting for 3 hours, the mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, and the crude product after filtration and concentration was purified by silica gel column chromatography (petroleum ether / ethyl acetate 10:1 → 5:1) to obtain a light yellow oily product 15 (18.7 mg, yield 59%).

[0118] R f = 0.4 (petroleum ether / ethyl acetate = 5 / 1); IR (film) λ max 3471, 2951, 2854, 1653, 1596, 1155, 1072, 837 cm -1 ; 1H NMR (600 MHz, (CD3)2CO) δ 9.6 (s, 1H), 7.9 – 7.9 (m, 1H), 7.7 – 7.7(m, 2H), 7.4 (dd, J = 7.1, 1.8 Hz, 1H), 7.3 (d, J = 8.0 Hz, 2H), 7.1 (pd, J =7.1, 1.4 Hz, 2H), 6.0 (s, 1H), 5.6 (dd, J = 9.9, 4.3 Hz, 1H), 5.0 (d, J = 1.6Hz, 1H), 4.8 (d, J = 1.6 Hz, 1H), 4.6 (d, J = 3.7 Hz, 1H), 3.8 (ddt, J =11.9, 6.2, 2.9 Hz, 1H), 3.7 (dd, J = 14.2, 6.0 Hz, 1H), 3.0 (q, J = 5.5 Hz,1H), 2.9 (dd, J = 14.2, 11.5 Hz, 1H), 2.6 (dt, J = 13.5, 4.9 Hz, 1H), 2.4 (s,3H), 1.9 (ddd, J = 14.1, 10.0, 4.6 Hz, 1H), 0.9 (s, 9H), 0.2 (s, 3H), 0.2 (s,3H); 13 C NMR (150 MHz, (CD3)2CO) δ 146.6, 143.9, 140.9, 139.3, 135.7,130.2, 129.1, 128.4, 122.5, 120.3, 119.8, 112.3, 112.1, 109.2, 69.2, 68.2,55.9, 45.9, 45.4, 38.8, 26.5, 21.4, 18.8, -4.4; HRMS (ESI) calculated molecular weight C 29 H 38 N2O4SSi [M+H] + : 539.2394; Measured molecular weight: 539.2392.

[0119] Embodiment 11 Synthesis of compound 16

[0120] Compound 15 (180 mg, 0.33 mmol, 1.0 equiv.) was dissolved in 10 ml of ethylene glycol dimethyl ether. The temperature of the system was lowered to -78 °C and then lithium naphthalene solution (0.5 M ethylene glycol dimethyl ether solution, 3.3 ml, 1.65 mmol, 5.0 equiv.) was added. The system remained dark green and was stirred for 10 minutes before quenching with the addition of 1.0 ml of methanol. Triethylamine (0.14 ml, 0.99 mmol, 3.0 equiv.) and di-tert-butyl dicarbonate (0.23 ml, 0.99 mmol, 3.0 equiv.) were then added to the system in sequence. The system was heated to room temperature and stirred for 1 hour. Saturated ammonium chloride solution was then added to quench the solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, and the crude product after filtration and concentration was purified by silica gel column chromatography (petroleum ether / ethyl acetate 15:1 →10:1) to obtain a white solid product 16 (138.9 mg, yield 87%).

[0121] R f = 0.6 (petroleum ether / ethyl acetate = 5 / 1); [α]25 D = +16.1 (c = 0.31 in MeOH); IR (film) λ max 3473, 2927, 2856, 1664, 1558, 1417, 1159, 1072 cm -1 ; 1H NMR (600 MHz, (CD3)2CO) δ 9.5 (d, J = 17.0 Hz, 1H), 7.9 – 7.7 (m,1H), 7.4 (dd, J = 15.0, 6.9 Hz, 1H), 7.2 – 6.9 (m, 2H), 6.1 (d, J = 76.5 4.1 – 3.9 (m, 2H), 3.2(t, J = 5.5 Hz, 1H), 2.8 (dd, J = 13.2, 11.1 Hz, 1H), 2.8 – 2.5 (m, 1H), 2.0– 1.8 (m, 1H), 1.5 (d, J = 91.5 Hz, 9H), 1.0 (d, J = 8.0 Hz, 9H), 0.3 – 0.1(m, 6H); 13 C NMR (150 MHz, (CD3)2CO) δ 154.4, 154.3, 148.7, 148.2, 140.7,140.6, 135.7, 129.3, 129.2, 122.3, 120.1, 120.1, 120.0, 119.4, 112.2, 112.0,111.3, 110.6, 110.5, 110.0, 80.2, 79.7, 70.1, 69.7, 69.3, 69.3, 54.7, 53.1,45.8, 44.8, 43.9, 39.2, 38.7, 28.8, 28.6, 26.5, 26.4, 26.3, 18.8, -4.3, -4.4, -4.4; HRMS (ESI) calculated molecular weight C 27 H 40 N2O4Si [M+Na] + : 507.2650; Measured molecular weight: 507.2648.

[0122] Example 12 Synthesis of compound 19

[0123] Compound 16 (20 mg, 0.034 mmol, 1.0 equiv.) was dissolved in 5.0 ml of dichloromethane. 60 mg of diatomaceous earth was added to the system and the temperature was lowered to 0 °C. Then, pyridinium dichromate (65 mg, 0.17 mmol, 5.0 equiv.) was added. After reacting for 20 minutes, 5.0 ml of petroleum ether, 5.0 ml of ethyl acetate and 100 mg of diatomaceous earth were added. The mixture was warmed to room temperature and stirred for 10 minutes. The mixture was filtered through diatomaceous earth and the crude product obtained after spin drying was directly used for the next step.

[0124] Compound 18 (40 mg, 0.17 mmol, 5.0 equiv.) was dissolved in 3.0 ml tetrahydrofuran, the system was cooled to -78°C, potassium bis(trimethylsilyl)amide (1M in THF, 0.13 ml, 0.13 mmol, 4.0 equiv.) was then added, stirred for 1 hour, the crude product of compound 17 obtained in the previous step was dissolved in 1.0 ml tetrahydrofuran and slowly added to the system, then reacted at -78°C for 2 hours, warmed to room temperature and stirred for 30 minutes, then quenched with saturated ammonium chloride solution, and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 20:1 → 15:1) to obtain a yellow oily product 19 (9.5 mg, yield 57%).

[0125] R f = 0.65 (petroleum ether / ethyl acetate = 10 / 1); IR (film) λ max 3473, 2927, 2854, 1683, 1558,1163, 1095, 881, 837 cm -1 ; 1H NMR (400 MHz, CD2Cl2) δ 8.4 (s, 1H), 7.9 – 7.7 (m, 1H), 7.3 (t, J =7.8 Hz, 1H), 7.1 (q, J = 7.1 Hz, 2H), 6.1 (d, J = 55.2 Hz, 1H), 5.6 (t, J =7.6 Hz, 1H), 5.3 (d, J = 4.8 Hz, 1H), 5.1 – 4.7 (m, 2H), 4.3 (dd, J = 44.2,15.6 Hz, 1H), 3.9 (d, J = 6.3 Hz, 1H), 3.6 (dd, J = 38.5, 15.9 Hz, 1H), 2.4(ddd, J = 11.7, 6.5, 4.8 Hz, 1H), 2.1 – 2.0 (m, 1H), 1.7 (dt, J = 9.2, 4.6Hz, 3H), 1.5 (dd, J = 48.4, 25.6 Hz, 9H), 1.0 (d, J = 2.3 Hz, 9H), 0.2 (d, J= 14.6 Hz, 6H); 13 C NMR (100 MHz, CD2Cl2) δ 153.6, 148.0, 139.3, 134.4, 133.9, 121.7,121.3, 119.5, 118.6, 110.7, 108.3, 79.8, 68.5, 52.2, 47.3, 45.9, 44.6, 40.4,28.3, 28.2, 28.1, 25.7, 25.7, 18.1, 12.0, -4.7, -5.1; HRMS (ESI) calculated molecular weight C 29 H 42 N2O3Si [M+H] + : 495.3037; Measured molecular weight: 495.3034.

[0126] Embodiment 13 Synthesis of compound 1

[0127] Compound 19 (9.5 mg, 0.019 mmol, 1.0 equiv.) was dissolved in 2.0 ml of tetrahydrofuran, the system was cooled to 0 °C and diisobutylaluminum hydride (1.0 M tetrahydrofuran solution, 0.1 ml, 0.1 mmol, 5.2 equiv.) was added, then the temperature was raised to 50 °C and stirred for 30 minutes, then cooled to 0 °C, 60 μL of water, 60 μL of 15% sodium hydroxide solution, and 150 μL of water were added in sequence, and then stirred at room temperature for 30 minutes, 20 mg of anhydrous magnesium sulfate was added, and after stirring for 10 minutes, filtration was performed using celite, and the crude product of compound 20 was obtained by spin drying, which was directly carried out to the next step.

[0128] The crude product obtained in the previous step was dissolved in 2.0 ml of dichloromethane, and then tetrabutylammonium fluoride trihydrate (7.9 mg, 0.028 mmol, 1.5 equiv.) was added to the system. After reacting at room temperature for 5 hours, active manganese dioxide (17 mg, 0.19 mmol, 10.0 equiv.) was added to the system. After reacting for 30 minutes, it was filtered with diatomaceous earth. After being spin-dried, the crude product was purified by silica gel column chromatography (ethyl acetate / methanol 20:1 → 10:1) to obtain a white solid product 1 (2.8 mg, yield 61%).

[0129] R f = 0.5 (ethyl acetate / methanol = 10 / 1); IR (film) λ max 2692, 2924, 1653, 1558, 1261, 1093, 1020, 798 cm -1 ; 1H NMR (600 MHz, CD3CN) δ 9.8 (s, 1H), 7.8 (dt, J = 8.2, 1.0 Hz, 1H), 7.5 (dt, J = 8.4, 1.0 Hz, 1H), 7.3 (ddd, J = 8.2, 6.9, 1.1 Hz, 1H), 7.2 (ddd,J = 8.0, 6.9, 1.0 Hz, 1H), 5.4 – 5.3 (m, 1H), 5.1 – 5.1 (m, 2H), 5.0 (s, 1H),3.8 (t, J = 4.6 Hz, 1H), 3.0 – 2.9 (m, 2H), 2.8 (dd, J = 16.8, 3.9 Hz, 1H), 2.8 (d, J = 14.5 Hz, 1H), 2.1 (s, 3H), 1.7 (dd, J = 6.9, 2.2 Hz, 3H); 13 C NMR (150 MHz, CD3CN) δ 194.5, 147.5, 137.6, 137.2, 135.2, 128.7,126.9, 122.6, 121.3, 121.0, 117.8, 113.1, 111.0, 62.1, 54.0, 51.3, 42.5,39.8, 12.1; HRMS (ESI) calculated molecular weight C 19 H 20 N2O [M+H] + : 293.1648; Measured molecular weight: 293.1646.

[0130] The above are only a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. An intermediate compound for synthesizing Ervitsine, characterized in that: The intermediate compounds include compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 14, compound 15, compound 16, compound 17, compound 18, compound 19, and compound 20, corresponding to the structures shown below: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 2. The method for preparing the intermediate compound according to claim 1, characterized in that: The preparation method of compound 4 comprises: A mixture containing 3-bromofuran, solvent 1, lithium diisopropylamide, benzyl chloromethyl ether, n-butyl lithium, and compound 3 is reacted with 1 to obtain the compound 4; The compound 3 has the structure shown below: ； Preferably, the halogenated furan is 3-bromofuran; Preferably, the solvent 1 is selected from at least one of diethyl ether and tetrahydrofuran; Preferably, the molar ratio of the halogenated furan, lithium diisopropylamide, benzyl chloromethyl ether, and n-butyl lithium is: 1: (1.1-1.3): (1.1-1.2): (1.2-1.4); Preferably, the molar ratio of the halogenated furan to the compound 3 is 1:1.3-1.5; Preferably, the molar volume ratio of the halogenated furan to the solvent 1 is 0.2-0.3:1 mol / L; Preferably, the temperature of the reaction 1 is -40 to -60°C, and the time of the reaction 1 is 2 to 5 hours.

3. The method for preparing the intermediate compound according to claim 1 or 2, characterized in that: The preparation method of compound 6 comprises: A mixture containing compound 4, compound 5, solvent 2, and potassium carbonate is reacted 2 to obtain the compound 6; The compound 5 has the structure shown below: ； Preferably, the solvent 2 is acetone; Preferably, the molar ratio of the compound 4 to the compound 5 is 1:1.1-1.2; Preferably, the molar ratio of the compound 4 to the potassium carbonate is 1:2.5-3.0; Preferably, the molar volume ratio of the compound 4 to the solvent 2 is 0.1-0.2:1 mol / L; Preferably, the temperature of reaction 2 is 50-55°C, and the time of reaction 2 is 10-12h; Preferably, the preparation method of the compound 7 comprises: reacting a mixture containing compound 6, solvent 3 and sodium borohydride by reaction 3 to obtain the compound 7; Preferably, the solvent 3 is a mixed solvent, the mixed solvent is tetrahydrofuran and water, and the volume ratio of tetrahydrofuran to water is 4:1; Preferably, the molar volume ratio of the compound 6 to the solvent 3 is 0.1-0.2:1 mol / L; Preferably, the molar ratio of the compound 6 to the sodium borohydride is 1:1.0-1.5; Preferably, the temperature of reaction 3 is 0-25°C, and the time of reaction 3 is 0.5-2h; Preferably, the preparation method of the compound 8 comprises: reacting a mixture containing compound 7, solvent 4, 2.6-lutidine, triisopropylsilyl trifluoromethanesulfonate, and potassium tert-butoxide by reaction 4 to obtain the compound 8; Preferably, the solvent 4 is tetrahydrofuran; Preferably, the molar ratio of the compound 7, 2,6-dimethylpyridine, triisopropylsilyl trifluoromethanesulfonate, and potassium tert-butoxide is: 1: (2.5-3): (1.1-1.2): (1.3-1.5); Preferably, the molar volume ratio of the compound 7 to the solvent 4 is 0.07-0.2:1 mol / L; Preferably, the temperature of reaction 4 is 0-25° C., and the time of reaction 4 is 0.5-3 h.

4. The method for preparing the intermediate compound according to any one of claims 1 to 3, characterized in that: The preparation method of compound 9 comprises: The mixture containing compound 8, solvent 5 and acetone peroxide is reacted 5 to obtain the compound 9; Preferably, the molar ratio of the compound 8 to the acetone peroxide is 1:2.5-3.0; Preferably, the molar volume ratio of the compound 8 to the solvent 5 is 0.001-0.05:1 mol / L; Preferably, the solvent 5 is dichloromethane; Preferably, the temperature of the reaction 5 is -78 to -40°C, and the time of the reaction 5 is 0.2 to 0.5h; Preferably, the preparation method of the compound 10 comprises: reacting a mixture containing compound 9, solvent 6, palladium carbon, triphenylphosphine, imidazole and iodine in a hydrogen atmosphere to obtain compound 10; Preferably, the molar ratio of the compound 9, palladium carbon, triphenylphosphine, imidazole and iodine is: 1: (0.1-0.15): (2.5-3): (2.5-3): (1.5-2); Preferably, the solvent 6 is toluene; Preferably, the molar volume ratio of the compound 9 to the solvent 6 is 0.03-0.05:1 mol / L; Preferably, the temperature of the reaction 6 is 20-30°C, and the reaction time is 1-2h; Preferably, the preparation method of the compound 11 comprises: reacting a mixture containing the compound 10, the solvent 7, and zinc powder with 7 to obtain the compound 11; Preferably, the solvent 7 comprises isopropanol, tert-butanol and water, isopropanol: tert-butanol: water = 10 ml: 10 ml: 0.2 ml; Preferably, the molar ratio of the compound 10 to the zinc powder is 1:10.0-12.0; Preferably, the molar volume ratio of the compound 10 to the solvent 7 is 0.01-0.02:1 mol / L; Preferably, the temperature of reaction 7 is 80-95° C., and the time of reaction 7 is 2-5 h.

5. The method for preparing the intermediate compound according to any one of claims 1 to 4, characterized in that: The preparation method of the compound 12 comprises: A mixture containing compound 11, solvent 8, 2,6-lutidine, tert-butyldimethylsilyl trifluoromethanesulfonate, p-toluenesulfonyl hydrazide, and acetic acid is reacted with 8 to obtain the compound 12; Preferably, the solvent 8 is 1.2-dichloroethane; Preferably, the molar ratio of the compound 11, 2,6-dimethylpyridine, tert-butyldimethylsilyl trifluoromethanesulfonate, and p-toluenesulfonyl hydrazide is: 1: (1.6-2.0): (1.5-1.8): (1.5-2.0); Preferably, the molar volume ratio of the compound 11 to the solvent 8 is 0.06-0.1:1 mol / L; Preferably, the molar volume ratio of the compound 11 to the acetic acid is 20-35:1 mol / L; Preferably, the temperature of the reaction 8 is 0-50°C, and the time of the reaction 8 is 5min-12h; Preferably, the preparation method of the compound 14 comprises: reacting a mixture containing the compound 12, tetrakistriphenylphosphine palladium, o-iodoaniline, potassium carbonate and toluene with reaction 9 to obtain the compound 14; Preferably, the molar ratio of the compound 12, tetrakistriphenylphosphine palladium, o-iodoaniline, and potassium carbonate is: 1: (0.1-0.12): (3.3-3.5): (4.0-5.0); Preferably, the molar volume ratio of the compound 12 to the toluene is 0.05-0.1:1 mol / L; Preferably, the temperature of the reaction 9 is 110-120° C., and the time of the reaction 8 is 10-18 h.

6. The method for preparing the intermediate compound according to any one of claims 1 to 5, characterized in that: The preparation method of compound 15 comprises: A mixture containing compound 14, solvent 9, iodobenzene trifluoroacetate and tetrabutylammonium fluoride is reacted with 10 to obtain the compound 15; Preferably, the solvent 9 is tetrahydrofuran; Preferably, the molar ratio of the compound 14, iodobenzene trifluoroacetate, and tetrabutylammonium fluoride is: 1: (1.3-1.5): (4.5-5.5); Preferably, the molar volume ratio of the compound 14 to the solvent 9 is 0.01-0.05:1 mol / L; Preferably, the temperature of the reaction 10 is -20 to 0°C, and the reaction time is 10 min to 3 h; Preferably, the preparation method of the compound 16 comprises: reacting a mixture containing the compound 15, the solvent 10, lithium naphthalene, triethylamine, and di-tert-butyl dicarbonate with 11 to obtain the compound 16; Preferably, the molar ratio of the compound 15, lithium naphthalene, triethylamine, and di-tert-butyl dicarbonate is: 1: (5.0-10.0): (2.5-3.0): (2.5-3.0); Preferably, the molar volume ratio of the compound 15 to the solvent 10 is 0.03-0.1:1 mol / L; Preferably, the solvent 10 is selected from at least one of ethylene glycol dimethyl ether and tetrahydrofuran; Preferably, the temperature of the reaction 11 is -78 to -40°C, and the time of the reaction 11 is 10 min to 0.5 h.

7. The method for preparing the intermediate compound according to any one of claims 1 to 6, characterized in that: The preparation method of compound 19 comprises the following steps: S1: reacting a mixture containing compound 16, solvent 11, and pyridinium dichromate with 12 to obtain a product containing compound 17; S2: dissolving the product containing compound 17 and adding it to a mixture containing compound 18, solvent 12, and potassium bis(trimethylsilyl)amide to react 13 to obtain compound 19; Preferably, in step S1, the molar ratio of the compound 16 to the pyridinium dichromate is 1:5.0-6.0; Preferably, in step S1, the molar volume ratio of the compound 16 to the solvent 11 is 0.006-0.01:1 mol / L; Preferably, in step S1, the solvent 11 is dichloromethane; Preferably, in step S1, the temperature of reaction 12 is 0-25°C, and the time of reaction 12 is 20min-2h; Preferably, in step S2, the molar ratio of the compound 18 to the potassium bis(trimethylsilyl)amide is 1:0.8-1.0; Preferably, in step S2, the molar volume ratio of the compound 18 to the solvent 12 is 0.05-0.1:1 mol / L; Preferably, in step S2, the solvent 12 is tetrahydrofuran; Preferably, in step S2, the temperature of reaction 13 is -78 to 25°C, and the time of reaction 13 is 1 h to 3 h.

8. A method for synthesizing Ervitsine, characterized in that: The synthesis method of Ervitsine comprises the following steps: Step a: reacting a mixture containing compound 19, solvent 13 and diisobutylaluminum hydride with 14 to obtain a product containing compound 20; Step b: After dissolving the product containing compound 20, tetrabutylammonium fluoride and manganese dioxide are added, and the reaction is carried out to obtain the Ervitsine; The compound 19 is consistent with the compound 19 described in claim 7; The compound 19 is prepared by the preparation method of compound 19 in claim 7.

9. The synthesis method according to claim 8, characterized in that In the step a, the molar ratio of the compound 19 to the diisobutylaluminum hydride is 1:4.0-5.0; Preferably, in step a, the molar volume ratio of the compound 19 to the solvent 13 is 0.001-0.02:1 mol / L; Preferably, in step a, the solvent 13 is tetrahydrofuran; Preferably, in step a, the temperature of reaction 14 is 0-50° C., and the time of reaction 14 is 0.5 h-1 h; Preferably, in the step b, the molar ratio of the compound 19 to the tetrabutylammonium fluoride is 1:1.2-1.5; Preferably, in the step b, the molar ratio of the compound 19 to the manganese dioxide is 1:10.0-12.0; Preferably, in the step b, the temperature of the reaction 15 is 20-30° C., and the time of the reaction 15 is 0.5 h-1 h.

10. A total synthesis method for synthesizing Ervitsine, characterized in that: The synthetic route of the total synthesis method of Ervitsine is as follows: ； Among them, compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 14, compound 15, compound 16, compound 17, compound 18, compound 19, and compound 20 in the synthetic route are consistent with compound 4, compound 6, compound 7, compound 8, compound 9, compound 10, compound 11, compound 12, compound 14, compound 15, compound 16, compound 17, compound 18, compound 19, and compound 20 described in claims 1 to 9.

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