Efficient preparation method of tetrahydrofuran type lignan Sumatranin A

Abstract

The invention provides an efficient preparation method of tetrahydrofuran type lignan Sumatranin A. The efficient preparation method specifically comprises the following steps: removing methyl protection from asaraldehyde to obtain a compound 1; performing benzyl protection to obtain a compound 2; carrying out continuous Wittig reaction to obtain a compound 3; reacting SN2 among molecules to obtain a cyclization precursor 4; an intermediate 5 is obtained through Ni catalysis series cyclization; removing benzyl protection to obtain a compound 6; and finally, carrying out ring closing under an acidic condition to obtain the tetrahydrofuran type lignan Sumatranin A. The preparation method has the three characteristics of high yield, low cost and short route; the total synthesis of the tetrahydrofuran type lignan Sumatranin A racemate serving as a natural active medicine is realized; good popularization and application prospects are realized.

Description

Technical Field

[0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a high-efficiency preparation method of tetrahydrofuran-type lignan Sumatranin A. Background Art

[0002] In 2023, a new type of tetrahydrofuran-type lignan Sumatranins was isolated and extracted from the Close-flowered Tree by the team of Academician Yue Jianmin. Activity studies have shown that this family of molecules has an immunosuppressive effect on cona-induced T lymphocyte proliferation and lipopolysaccharide (LPS)-induced B lymphocyte proliferation. At present, this type of molecule can only be obtained by separation and preparation, and no one has yet involved the chemical synthesis route. Since the 21st century, the pharmaceutical industry has flourished, and the chemical synthesis route of small molecules has also received widespread attention. Therefore, organic synthesis methods are used to achieve the total synthesis of Sumatranin A and its family molecules.

[0003] Based on the structural analysis of the target molecule, commercially available aromatic fragments are used as starting materials, and the cyclization precursor is efficiently constructed through multi-step reactions. The key ring-closure reaction is intended to be achieved using photo-Ni catalysis promoted by green chemistry in recent years; the final molecule can be obtained by simply transforming the polycyclic intermediates.

[0004] The present invention aims to synthesize a tetrahydrofuran-type lignan Sumatranin A newly separated from Cleome sphenanthera through a short route and an environmentally friendly method. Summary of the invention

[0005] The present invention mainly overcomes the shortcomings of the prior art and proposes an efficient preparation method of tetrahydrofuran-type lignan Sumatranin A, which specifically comprises: removing the methyl protection of asarone to obtain compound 1; obtaining compound 2 through benzyl protection; obtaining compound 3 through continuous Wittig reaction; and obtaining compound 4 through intermolecular S N 2 to obtain the cyclization precursor 4; the intermediate 5 is obtained by Ni-catalyzed tandem cyclization; the benzyl protection is removed to obtain compound 6; finally, the tetrahydrofuran-type lignan Sumatranin A is obtained by ring closure under acidic conditions; the preparation method has the three characteristics of high yield, low cost and short route; it realizes the total synthesis of the natural active drug tetrahydrofuran-type lignan Sumatranin A racemate; and has excellent prospects for promotion and application.

[0006] In order to achieve the above technical objectives, the technical solution adopted by the present invention is:

[0007] An efficient preparation method of tetrahydrofuran-type lignan Sumatranin A, the reaction process is as follows:

[0008]

[0009] The synthesis method comprises steps 1 to 7:

[0010] Specific:

[0011] Step 1: Under the conditions of aluminum chloride as acid and dichloromethane as solvent, the compound asarone is demethylated to obtain compound 1;

[0012] Step 2: Compound 1, benzyl bromide, potassium carbonate and copper oxide are heated in acetonitrile solvent to obtain compound 2;

[0013] Step 3: Compound 2 undergoes Wittig reaction in the presence of potassium tert-butoxide as a base, (methoxymethyl)-triphenylphosphine chloride and tetrahydrofuran, and then is treated with hydrochloric acid and subjected to Wittig reaction to obtain compound 3;

[0014] Step 4: Compound 3 is treated with NBS and allyl alcohol to obtain compound 4;

[0015] Step 5: Compound 4 and 5-benzyloxy-6-iodopiperidinol undergo tandem cyclization under the conditions of nickel chloride, zinc powder, pyridine and acetonitrile to obtain compound 5;

[0016] Step 6: Compound 5 is treated with palladium hydroxide on carbon to remove the benzyl protecting group to obtain compound 6;

[0017] Step 7: Compound 6 is treated with boron trifluoride etherate as an acid and subjected to ring closure under low temperature conditions to obtain the tetrahydrofuran-type lignan Sumatranin A.

[0018] Furthermore, the structural formulas of the compound asarone, compounds 1 to 6, and tetrahydrofuran-type lignan Sumatranin A are:

[0019]

[0020] Furthermore, the specific synthesis method of step 1 is:

[0021] The asarone aldehyde is demethylated to obtain compound 1, which specifically comprises:

[0022] After replacing the argon, add asarone and aluminum chloride to the reaction bottle, add solvent dichloromethane at 0°C to 10°C; then transfer to 20°C to 35°C for stirring reaction, react at this temperature for 9 to 19 hours, and react under normal pressure; after the reaction, add concentrated HCl for quenching at 0°C to 10°C with vigorous stirring, extract the organic layer with DCM, wash with distilled water and saturated brine, add anhydrous Na2SO4 for drying, concentrate under reduced pressure, and crystallize with ethyl acetate to obtain compound 1;

[0023] The molar ratio of asarone to aluminum chloride is 101.9-120.0:500.0-550.0.

[0024] Furthermore, the specific synthesis method of step 2 is:

[0025] Compound 1 is protected with bromobenzyl to obtain compound 2, specifically comprising:

[0026] After replacing argon, potassium carbonate, copper oxide and compound 1 dissolved in acetonitrile solvent were added to the reaction bottle; the temperature was raised to 60°C to 80°C after transfer to an oil bath and benzyl bromide was added. After reacting for 4 to 6 hours, the mixture was filtered with a sand core funnel, and the filtrate was concentrated and slurried with petroleum ether to obtain compound 2;

[0027] The molar ratio of the compound 1, potassium carbonate, copper oxide and benzyl bromide is: 100.0-110.5-: 300.0-333.5: 10.0-11.1: 220.0-244.6.

[0028] Furthermore, the specific synthesis method of step 3 is:

[0029] Compound 2 undergoes a continuous Wittig reaction to obtain compound 3, specifically comprising:

[0030] After replacing argon, potassium tert-butoxide and (methoxymethyl)-triphenylphosphonium chloride were added to the reaction flask, tetrahydrofuran was added at 0°C to 10°C, and the mixture was stirred for 20 to 40 minutes, followed by the addition of compound 2 dissolved in tetrahydrofuran; after reacting for 2 to 4 hours, ammonium chloride was added to quench the mixture, and tetrahydrofuran and hydrochloric acid were added after extraction with EtOAc, and the mixture was stirred at 30°C to 50°C for 2 to 3 hours, quenched with sodium bicarbonate, and extracted with EA. After concentration, the Wittig reaction was repeated again, and compound 3 was obtained after extraction with EtOAc and concentration and column chromatography. The column chromatography conditions were: petroleum ether to ethyl acetate = 40:1 to 30:1;

[0031] The molar ratio of the compound 2, potassium tert-butoxide, (methoxymethyl)-triphenylphosphonium chloride and hydrochloric acid is: 97.6-105.1: 224.4-241.6: 205.0-220.7: 975.9-1050.9.

[0032] Furthermore, the specific synthesis method of step 4 is:

[0033] Compound 3 was synthesized by intermolecular S N 2 to obtain compound 4, which specifically includes:

[0034] After replacing the argon, add allyl alcohol and compound 3 dissolved in dichloromethane to the reaction flask, cool to -30°C to -20°C, then add NBS in two batches within 10 to 15 minutes, and react for 30 to 40 minutes; after the reaction, add saturated sodium bicarbonate aqueous solution to quench, wash the aqueous phase with dichloromethane, wash the organic phase with distilled water and saturated brine, add anhydrous sodium sulfate to dry, concentrate under reduced pressure, and separate and purify by column chromatography, the eluent volume ratio is petroleum ether: ethyl acetate = 20:1 to 15:1, and compound 4 can be obtained;

[0035] The molar ratio of the compound 3, allyl alcohol and NBS is: 67.9-72.0: 203.7-216.0: 81.4-86.3.

[0036] Furthermore, the specific synthesis method of step 5 is:

[0037] Compound 4 is cyclized by Ni to obtain compound 5, which specifically includes:

[0038] After replacing the argon, nickel chloride, zinc powder and 4,4′-di-tert-butyl-2,2′-bipyridine are added to the reaction bottle, pyridine is used as a solvent, and the ligand is prepared by stirring at 50° C. to 80° C. for 15 to 25 minutes, and then compound 4 and 5-benzyloxy-6-iodopiperidinol dissolved in acetonitrile are added, and the reaction is carried out at this temperature for 2 to 4 hours; after the reaction is completed, distilled water is added to quench, and the mixture is washed with ethyl acetate, extracted with ethyl acetate, washed with distilled water and saturated brine, and dried with anhydrous sodium sulfate. After reduced pressure concentration, the mixture is separated and purified by column chromatography, and the eluent volume ratio is petroleum ether:ethyl acetate=8:1 to 5:1, and compound 5 can be obtained;

[0039] The molar ratio of the compound 4, 5-benzyloxy-6-iodopiperidinol, nickel chloride, zinc powder and 4,4'-di-tert-butyl-2,2'-bipyridine is: 3.6-4.2: 4.2-4.9: 3.6-4.2: 10.7-12.6: 3.6-4.2.

[0040] Furthermore, the specific synthesis method of step 6 is:

[0041] Compound 5 is deprotected from the benzyl group to obtain compound 6, which specifically comprises:

[0042] Add palladium hydroxide carbon and compound 5 dissolved in tetrahydrofuran into a reaction flask, and stir at 30°C to 50°C in a hydrogen environment for 4 to 8 hours; after the reaction, filter with a sand core funnel to recover palladium hydroxide carbon, and concentrate the product under reduced pressure and purify it by column chromatography, with the eluent volume ratio of petroleum ether: ethyl acetate = 3:1 to 2:1; to obtain compound 6;

[0043] The molar ratio of palladium hydroxide carbon to compound 5 is: 1.7-2.1: 0.6-0.7.

[0044] Furthermore, the specific synthesis method of step 7 is:

[0045] Compound 6 is acidified to obtain tetrahydrofuran-type lignan Sumatranin A, which specifically comprises:

[0046] Add compound 6 dissolved in dichloromethane to a reaction flask, add boron trifluoride ether at 0°C to 10°C, and stir for 10 to 30 minutes; after the reaction is completed, add saturated NaHCO3 to quench, extract with dichloromethane, wash with distilled water and saturated brine, dry the organic phase with anhydrous Na2SO4, concentrate under reduced pressure, and separate and purify by column chromatography, the eluent volume ratio is petroleum ether: ethyl acetate = 3:1 to 2:1, and tetrahydrofuran-type lignan Sumatranin A can be obtained;

[0047] The molar ratio of the compound 6 to boron trifluoride ether is 0.4-0.5: 0.4-0.6.

[0048] Beneficial Effects

[0049] Compared with the prior art, the present invention has the following advantages:

[0050] The present invention mainly overcomes the current situation of insufficient separation technology, and discloses a highly efficient preparation method of tetrahydrofuran-type lignan Sumatranin A, which specifically comprises: removing methyl protection from asarone to obtain compound 1; obtaining compound 2 through benzyl protection; obtaining compound 3 through continuous Wittig reaction; and obtaining compound 4 through intermolecular S N 2 reaction to obtain the cyclization precursor 4; Ni-catalyzed tandem cyclization to obtain the intermediate 5; remove the benzyl protection to obtain compound 6; and finally close the ring under acidic conditions to obtain Sumatranin A. This preparation method achieves the total synthesis of the natural active drug Sumatranin A racemate with the three characteristics of high yield, low cost and short route. Taking Sumatranin A molecule as the target, through the method of chemical synthesis, the traditional Ni-catalyzed tandem cyclization is designed as the key reaction to quickly and efficiently construct the dibenzyl furan ring [6,5,6] skeleton, develop a new method for constructing this structural unit, expand the substrate of this method, and apply this method to the synthesis of various natural furan lignans. This method is simple to operate, with cheap raw materials and short steps, which lays the foundation for the subsequent synthesis of other types of polycyclic furan lignans, reflecting the superiority of this method and has high practical value. In addition, the synthesis of Sumatranin A breaks the limitations of existing separation technology and provides new technology and direction for the subsequent synthesis and biological exploration of natural products. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1The synthetic route diagram of Sumatranin A in the embodiment of the present invention;

[0052] Figure 2 is the structural formula of asarone, compounds 1 to 6 and Sumatranin A in the examples. DETAILED DESCRIPTION

[0053] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0054] according to Figure 1 The synthetic route diagram shown in the figure is used to synthesize the compounds in the following examples, and the structural formulas of the compounds involved are Figure 2 shown.

[0055] Embodiment 1:

[0056] Step 1:

[0057] Take a 500mL two-necked bottle to dehumidify, add aluminum chloride (68.0g, 509.6mmol, 5.0equiv) to the bottle, and add asarone (20g, 101.9mmol) dissolved in dichloromethane (240ml) at 0°C. After slowly returning to room temperature, stir for 9h, pour the reaction mixture into 300g ice, and add 30mL concentrated hydrochloric acid. Separate the organic layer with DCM (200mL), extract the aqueous phase twice, collect the organic phase, dry it with anhydrous sodium sulfate, and concentrate it. Crystallize it with ethyl acetate to obtain 17g of green solid compound 1, with a yield of 99%. R f =0.6(petroleum ether / EtOAc=1:1).

[0058] Step 2:

[0059] Take a 500mL two-necked bottle to dehumidify, add compound 1 (17g, 101.1mmol), K2CO3 (42g, 303.3mmol, 3.0equiv) and CuO (808.8mg, 10.1mmol, 0.1equiv) into the bottle, and add MeCN (180ml) at room temperature. After stirring for 10min, add benzyl bromide (26mL, 222.4mmol, 2.2equiv). The reaction is completed after 4h of monitoring by TLC at 80℃, filter with sand core funnel, wash with ethyl acetate (200mL), and concentrate. Use petroleum ether to slurry to obtain 34.0g of dark yellow solid product compound 2, with a yield of 93%. R f =0.4(petroleum ether / EtOAc=4:1).

[0060] Step 3:

[0061] Take a 500 mL two-necked bottle, dehumidify, replace argon three times, add potassium tert-butoxide (98%, 22.5 g, 224.4 mmol, 2.3 equiv) and (methoxymethyl)triphenylphosphonium chloride (68.4 g, 205.0 mmol, 2.1 equiv), and replace argon three times again. Redistilled tetrahydrofuran (150 mL) was added at 0°C. After reacting at this temperature for 40 minutes, compound 2 (34 g, 97.6 mmol, 1.0 equiv) dissolved in dry tetrahydrofuran (150 mL) was added dropwise. The temperature was naturally raised from 0°C to room temperature. After 2 hours, a saturated ammonium chloride solution (50 mL) was added to quench the reaction. The mixture was extracted three times with ethyl acetate (300 mL), and then washed twice with water (200 mL) and once with a saturated sodium chloride solution (100 mL). The organic layer was collected, dried over anhydrous sodium sulfate, concentrated, and 3N HCl (325 mL, 975.9 mmol, 10.0 equiv) and tetrahydrofuran (300 mL) were added at room temperature. The mixture was reacted at 50°C for 3 h. After the reaction is completed, quench with saturated sodium bicarbonate, spin dry the excess solvent, extract with EA (300 mL) three times, wash twice with water (200 mL) and once with saturated sodium chloride solution (100 mL), collect the organic layer, add anhydrous sodium sulfate to dry, and concentrate. The obtained intermediate is not purified, take a 500 mL two-necked bottle, dehumidify, replace argon three times, add potassium tert-butoxide (98%, 18.2 g, 162.8 mmol, 2.0 equiv) and (methoxymethyl) triphenylphosphonium chloride (55.6 g, 162.8 mmol, 2.0 equiv), and replace argon three times again. Add redistilled tetrahydrofuran (150 mL) at 0°C, react at this temperature for 40 minutes, then add unpurified intermediate (29.5 g, 81.4 mmol, 1.0 equiv) dissolved in dry tetrahydrofuran (100 mL) dropwise, and naturally rise from 0°C to room temperature. After 4 hours, monitor the reaction. When the reaction is complete, add saturated ammonium chloride solution (50 mL) to quench the reaction, extract three times with ethyl acetate (300 mL), then wash twice with water (80 mL) and once with saturated sodium chloride solution (40 mL), collect the organic layer, dry over anhydrous sodium sulfate, concentrate, and column chromatograph. (Petroleum ether / EtOAc=40:1→Petroleum ether / EtOAc=25:1) to obtain light yellow oily liquid compound 3 (26.5 g, yield 65%, Z / E=1.4:1). f =0.6(petroleum ether / EtOAc=10:1).

[0062] Step 4:

[0063] Take a 500mL two-necked bottle to dehumidify, add compound 3 (26.5g, 67.9mmol), redistilled dichloromethane (300mL) and allyl alcohol (11.8g, 203.7mmol, 3.0equiv) at -20℃, stir for 10 minutes, add recrystallized NBS (14.5g, 81.4mmol, 1.2equiv) in batches, react for 30 minutes, monitor with a plate, if the reaction is over, quench the reaction with saturated sodium bicarbonate solution (30mL), extract three times with dichloromethane (150mL), wash twice with water (50mL) and once with saturated sodium chloride solution (50mL), collect the organic phase, dry with anhydrous sodium sulfate, concentrate, and column chromatography (Petroleum ether / EtOAc=20:1) to obtain a light yellow oily compound 4 (24.0g, yield 67%). f =0.5(petroleum ether / EtOAc=30:1).

[0064] Step 5:

[0065] A 10 mL double-necked round-bottom flask was dehumidified and replaced with argon three times. Anhydrous NiCl2 (463 mg, 3.6 mmol, 1.0 equiv), dtbpy (960 mg, 3.6 mmol, 1.0 equiv), and Zn powder (696 mg, 10.7 mmol, 3.0 equiv) were added at room temperature, and the argon was replaced again four times. Pyridine (8 mL) was added at room temperature, and the reaction flask was placed in a 53 ° C oil bath with a speed of 350 r / min and stirred for 20 minutes to obtain a black-red Ni (0) L complex. Compound 4 (1.9 g, 3.6 mmol) and 5-benzyloxy-6-iodopiperidinol (1.5 g, 4.2 mmol, 1.2 equiv) dissolved in acetonitrile (8 mL) were slowly added dropwise at room temperature. After the reaction was completed at 53 ° C for 4 h, water was added to quench the reaction. The mixture was washed with ethyl acetate (20 mL), the organic phases were combined and extracted twice with ethyl acetate (10 mL), washed 5 times with water (10 mL) and once with saturated sodium chloride solution (15 mL), dried over anhydrous sodium sulfate, concentrated and separated. Column chromatography (Petroleumether / EtOAc=8:1) gave compound 5 (744 mg, yield 31%) as a light yellow oily liquid. f =0.6(Petroleumether / EtOAc=3:1)

[0066] Step 6:

[0067] Dehumidify a 10mL two-necked round-bottom flask, add compound 5 (375mg, 0.56mmol) and Pd(OH)2 / C (1.17g, 1.67mmol, 3.0equiv, Pd 20% on carbon) into the two-necked flask. Add THF (6mL) at room temperature, replace H2 twice, use H2 balloon as H source, gradually raise the temperature to 50°C and react for 4 hours. After the reaction is completed by TLC detection, Pd(OH)2 / C is recovered by suction filtration, the filter cake is washed with ethyl acetate (10mL), and the filtrate is concentrated. Column chromatography separation (Petroleum ether / EtOAc=3:1) gives white solid compound 6 (100mg, yield 45%). f =0.55(Petroleum ether / EtOAc=1:1).

[0068] Step 7:

[0069] A 5 mL two-necked round-bottom flask was dehumidified, and compound 6 (142 mg, 0.35 mmol) and BF3·Et2O (55 mg, 0.39 mmol, 1.1 equiv) diluted with 1 mL DCM were added to the two-necked flask at -20°C. The reaction was completed after 5 min according to TLC detection, and the mixture was quenched with saturated NaHCO3 (2 mL), extracted twice with dichloromethane (2 mL), washed once with water (2 mL) and saturated sodium chloride solution (3 mL), dried over anhydrous sodium sulfate, and concentrated and separated. The product Sumatranin A (50 mg, yield 66%) was obtained by column chromatography separation (Petroleum ether / EtOAc=3:1). Rf=0.5 (Petroleum ether / EtOAc=1:1).

[0070] Its structure is characterized by TLC thin layer chromatography and nuclear magnetic resonance data. Specific as follows: 1 H NMR (400MHz, DMSO-d6) δ = 8.99 (s, 1H, OH), 8.78 (s, 1H, OH), 6.62 (s, 1H), 6.53 (s, 1H) ,6.40(s,1H),6.22(s,1H),5.86(s,2H),5.53(d,J=5.2Hz,1H),3.78(t,J=8.0Hz,1H) ,3.68(s,3H),3.49(t,J=8.0Hz,1H),2.73(dd,J=16.0,6.0Hz,1H),2.65(dd,J=13.2 ,6.0Hz,1H),2.45(dd,J=13.2,8.0Hz,1H),2.40–2.31(m,2H),2.36–2.28(m,1H)ppm.

[0071] In summary, the present invention mainly reports an efficient preparation method of Sumatranin A, which specifically comprises: removing the methyl protection of asarone aldehyde to obtain compound 1; obtaining compound 2 through benzyl protection; obtaining compound 3 through continuous Wittig reaction; and obtaining compound 4 through intermolecular S N 2 reaction to obtain the cyclization precursor 4; Ni-catalyzed tandem cyclization to obtain the intermediate 5; remove the benzyl protection to obtain compound 6; and finally close the ring under acidic conditions to obtain Sumatranin A. This preparation method achieves the total synthesis of the natural active drug Sumatranin A racemate with the three characteristics of high yield, low cost and short route. Taking Sumatranin A molecule as the target, through the method of chemical synthesis, the traditional Ni-catalyzed tandem cyclization is designed as the key reaction to quickly and efficiently construct the dibenzyl furan ring [6,5,6] skeleton, develop a new method for constructing this structural unit, expand the substrate of this method, and apply this method to the synthesis of various natural furan lignans. This method is simple to operate, with cheap raw materials and short steps, which lays the foundation for the subsequent synthesis of other types of polycyclic furan lignans, reflecting the superiority of this method and has high practical value. In addition, the synthesis of Sumatranin A breaks the limitations of existing separation technology and provides new technology and direction for the subsequent synthesis and biological exploration of natural products.

[0072] Finally, it should be noted that the terms "comprises," "includes," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements that are inherent to such process, method, article, or apparatus.

[0073] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0074] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. An efficient preparation method of tetrahydrofuran-type lignan Sumatranin A, characterized in that: The reaction process of the preparation method is as follows: The synthesis method comprises steps 1 to 7: Specific: Step 1: Under the conditions of aluminum chloride as acid and dichloromethane as solvent, the compound asarone is demethylated to obtain compound 1; Step 2: Compound 1, benzyl bromide, potassium carbonate and copper oxide are heated in acetonitrile solvent to obtain compound 2; Step 3: Compound 2 undergoes Wittig reaction in the presence of potassium tert-butoxide as a base, (methoxymethyl)-triphenylphosphine chloride and tetrahydrofuran, and then is treated with hydrochloric acid and subjected to Wittig reaction to obtain compound 3; Step 4: Compound 3 is treated with NBS and allyl alcohol to obtain compound 4; Step 5: Compound 4 and 5-benzyloxy-6-iodopiperidinol undergo tandem cyclization under the conditions of nickel chloride, zinc powder, pyridine and acetonitrile to obtain compound 5; Step 6: Compound 5 is treated with palladium hydroxide on carbon to remove the benzyl protecting group to obtain compound 6; Step 7: Compound 6 is treated with boron trifluoride etherate as an acid and subjected to ring closure under low temperature conditions to obtain the tetrahydrofuran-type lignan Sumatranin A.

2. The method for efficiently preparing a tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The structural formulas of the compound asarone, compounds 1 to 6 and tetrahydrofuran-type lignan Sumatranin A are:

3. The method for efficiently preparing a tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 1 is: The asarone aldehyde is demethylated to obtain compound 1, which specifically comprises: After replacing the argon, add asarone and aluminum chloride to the reaction bottle, add solvent dichloromethane at 0°C to 10°C; then transfer to 20°C to 35°C for stirring reaction, react at this temperature for 9 to 19 hours, and react under normal pressure; after the reaction, add concentrated HCl for quenching at 0°C to 10°C with vigorous stirring, extract the organic layer with DCM, wash with distilled water and saturated brine, add anhydrous Na2SO4 for drying, concentrate under reduced pressure, and crystallize with ethyl acetate to obtain compound 1; The molar ratio of asarone to aluminum chloride is 101.9-120.0:500.0-550.

0.

4. The method for efficiently preparing a tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 2 is: Compound 1 is protected with bromobenzyl to obtain compound 2, specifically comprising: After replacing argon, potassium carbonate, copper oxide and compound 1 dissolved in acetonitrile solvent were added to the reaction bottle; the temperature was raised to 60°C to 80°C after transfer to an oil bath and benzyl bromide was added. After reacting for 4 to 6 hours, the mixture was filtered with a sand core funnel, and the filtrate was concentrated and slurried with petroleum ether to obtain compound 2; The molar ratio of the compound 1, potassium carbonate, copper oxide and benzyl bromide is: 100.0-110.5-: 300.0-333.5: 10.0-11.1: 220.0-244.

6.

5. The method for efficiently preparing the tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 3 is: Compound 2 undergoes a continuous wittig reaction to obtain compound 3, specifically comprising: After replacing argon, potassium tert-butoxide and (methoxymethyl)-triphenylphosphonium chloride were added to the reaction flask, tetrahydrofuran was added at 0°C to 10°C, and the mixture was stirred for 20 to 40 minutes, followed by the addition of compound 2 dissolved in tetrahydrofuran; after reacting for 2 to 4 hours, ammonium chloride was added to quench the mixture, and tetrahydrofuran and hydrochloric acid were added after extraction with EtOAc, and the mixture was stirred at 30°C to 50°C for 2 to 3 hours, quenched with sodium bicarbonate, and extracted with EA. After concentration, the wittig reaction was repeated again, and compound 3 was obtained after extraction with EtOAc and concentration and column chromatography. The column chromatography conditions were: petroleum ether to ethyl acetate = 40:1 to 30:1; The molar ratio of the compound 2, potassium tert-butoxide, (methoxymethyl)-triphenylphosphonium chloride and hydrochloric acid is: 97.6-105.1: 224.4-241.6: 205.0-220.7: 975.9-1050.

9.

6. The method for efficiently preparing the tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 4 is: Compound 3 was synthesized by intermolecular S N 2 to obtain compound 4, which specifically includes: After replacing the argon, add allyl alcohol and compound 3 dissolved in dichloromethane to the reaction flask, cool to -30°C to -20°C, then add NBS in two batches within 10 to 15 minutes, and react for 30 to 40 minutes; after the reaction, add saturated sodium bicarbonate aqueous solution to quench, wash the aqueous phase with dichloromethane, wash the organic phase with distilled water and saturated brine, add anhydrous sodium sulfate to dry, concentrate under reduced pressure, and separate and purify by column chromatography, the eluent volume ratio is petroleum ether: ethyl acetate = 20:1 to 15:1, and compound 4 can be obtained; The molar ratio of the compound 3, allyl alcohol and NBS is: 67.9-72.0: 203.7-216.0: 81.4-86.

3.

7. The method for efficiently preparing the tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 5 is: Compound 4 is cyclized by Ni to obtain compound 5, which specifically includes: After replacing the argon, nickel chloride, zinc powder and 4,4′-di-tert-butyl-2,2′-bipyridine are added to the reaction bottle, pyridine is used as a solvent, and the ligand is prepared by stirring at 50° C. to 80° C. for 15 to 25 minutes, and then compound 4 and 5-benzyloxy-6-iodopiperidinol dissolved in acetonitrile are added, and the reaction is carried out at this temperature for 2 to 4 hours; after the reaction is completed, distilled water is added to quench, and the mixture is washed with ethyl acetate, extracted with ethyl acetate, washed with distilled water and saturated brine, and dried with anhydrous sodium sulfate. After reduced pressure concentration, the mixture is separated and purified by column chromatography, and the eluent volume ratio is petroleum ether:ethyl acetate=8:1 to 5:1, and compound 5 can be obtained; The molar ratio of the compound 4, 5-benzyloxy-6-iodopiperidinol, nickel chloride, zinc powder and 4,4'-di-tert-butyl-2,2'-bipyridine is: 3.6-4.2: 4.2-4.9: 3.6-4.2: 10.7-12.6: 3.6-4.

2.

8. The method for efficiently preparing the tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 6 is: Compound 5 is deprotected from the benzyl group to obtain compound 6, which specifically comprises: Add palladium hydroxide carbon and compound 5 dissolved in tetrahydrofuran into a reaction flask, and stir at 30°C to 50°C in a hydrogen environment for 4 to 8 hours; after the reaction, filter with a sand core funnel to recover palladium hydroxide carbon, and concentrate the product under reduced pressure and purify it by column chromatography, with the eluent volume ratio of petroleum ether: ethyl acetate = 3:1 to 2:1; to obtain compound 6; The molar ratio of palladium hydroxide carbon to compound 5 is: 1.7-2.1: 0.6-0.

7.

9. The method for efficiently preparing the tetrahydrofuran-type lignan Sumatranin A as claimed in claim 1, characterized in that: The specific synthesis method of step 7 is: Compound 6 is acidified to obtain tetrahydrofuran-type lignan Sumatranin A, which specifically includes: Add compound 6 dissolved in dichloromethane to a reaction flask, add boron trifluoride ether at 0°C to 10°C, and stir for 10 to 30 minutes; after the reaction is completed, add saturated NaHCO3 to quench, extract with dichloromethane, wash with distilled water and saturated brine, dry the organic phase with anhydrous Na2SO4, concentrate under reduced pressure, and separate and purify by column chromatography, the eluent volume ratio is petroleum ether: ethyl acetate = 3:1 to 2:1, and tetrahydrofuran-type lignan Sumatranin A can be obtained; The molar ratio of the compound 6 to boron trifluoride ether is 0.4-0.5: 0.4-0.6.

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