CN111662260B - Synthetic method of natural product saffloneoside - Google Patents

Synthetic method of natural product saffloneoside Download PDF

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CN111662260B
CN111662260B CN201910164493.5A CN201910164493A CN111662260B CN 111662260 B CN111662260 B CN 111662260B CN 201910164493 A CN201910164493 A CN 201910164493A CN 111662260 B CN111662260 B CN 111662260B
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safloneoside
ethyl acetate
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张培成
高万
杨桠楠
姜建双
冯子明
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Abstract

The invention belongs to the fields of organic synthesis and pharmaceutical chemistry, and relates to a total synthesis method of natural product safloneoside. The invention takes 2,4, 6-trihydroxy acetophenone as raw material, and completes the total synthesis of the compound safloneoside through seven steps of reactions. The total synthesis method has the advantages of easily available raw materials, stable intermediates, easy control of reaction and important reference and practical values for preparing the natural product, namely the safloneoside in large quantities. The prepared compound safloneoside has remarkable cerebral ischemia injury resistance activity, can be used as a raw material of medicines, and can be further used for preparing medicines for treating ischemic cerebral apoplexy.

Description

Synthetic method of natural product saffloneoside
Technical Field
The invention belongs to the fields of organic synthesis and pharmaceutical chemistry, relates to a natural product with anti-cerebral ischemia injury activity, and in particular relates to a total synthesis method of a natural chalcone carbon glycoside compound safloneoside with remarkable anti-cerebral ischemia injury activity.
Background
Cerebral ischemia disease is a major killer of modern human health and life, is one of three diseases causing human death, and especially has the greatest influence on the elderly. In China, cerebral ischemia diseases become the first disability and death cause at present, and the morbidity is in a trend of increasing year by year. Research shows that 150 to 200 thousands of new strokes occur in China each year, and most of the strokes are ischemic strokes. Along with the rapid development of medical science and technology, the diagnosis and treatment level of the cerebrovascular disease is continuously improved, but the disease has the characteristics of high morbidity, high recurrence rate, high disability rate and high death rate. Therefore, further research on the pathogenesis of ischemic cerebrovascular diseases and development of effective therapeutic drugs are increasingly urgent. There is no clinically effective treatment for such diseases. The research of the high-efficiency low-toxicity multi-target multi-link anti-cerebral ischemia injury drug is a hot spot problem of research at home and abroad in recent years. At present, medicines for resisting cerebral ischemia are relatively few in clinic, so that research for searching medicines for treating heart cerebral infarction diseases with high efficiency and low toxicity from abundant natural medicines has become a research hotspot in the current international medical community.
Figure BDA0001985843890000011
The traditional Chinese medicine has long history, definite curative effect and rich chemical diversity information, and is an important source of innovative medicines. Safflower is a traditional Chinese medicine for promoting blood circulation to remove blood stasis, has unique efficacy in treating cerebrovascular diseases, and safflower injection has been used for treating apoplexy clinically. The present subject group was isolated from safflower injection at an early stage to obtain a novel structural quinone type chalcone carboside compound named safflower neoside (Zhang Jinlan, zhu Haibo, zhang Peicheng, chengxin, jiang Jianshuang, zhang Ling, kai, feng Ziming, zhang Yinghao. Safflower effective fraction, its preparation method, pharmaceutical composition and use: 200710065070.5), and its activity was measured. In vivo pharmacological experiments show that the safloneoside improves the neurobehavioral symptoms of cerebral ischemia rats in a dose-dependent manner, reduces cerebral infarction area, has stronger anti-cerebral ischemia injury effect (Zhang Jinlan, zhu Haibo, zhang Peicheng, chengxin, jiang Jianshuang, zhang Ling, kai, feng Ziming, zhang Yinghao. Novel compounds separated from safflower, preparation methods, pharmaceutical compositions and applications thereof: 200710065069.2);
research shows that the compound safloneoside has low content in safflower, so that the deep development and utilization of the compound safloneoside are limited in practice, and researchers try to prepare the compound safloneoside by a chemical synthesis method, so that the compound safloneoside is a convenient and effective way. The inventor of the application, through looking up the literature, has not been reported to date about the total synthesis method of the compound safloneoside; meanwhile, the compound safloneoside belongs to natural quinoid chalcone carbon glycoside compounds, quinoid chalcone carbon glycoside is a difficult point of synthesis in the technical field at present, and no document report of Guan Kun type carbon glycoside exists.
Disclosure of Invention
The invention aims to overcome the defects existing in the prior art and provides a method for synthesizing a natural product; in particular to a method for synthesizing natural products with anti-cerebral ischemia injury activity, in particular to a method for fully synthesizing natural chalcone glycoside compounds safloneoside with remarkable anti-cerebral ischemia injury activity.
The synthesis method takes 2,4, 6-trihydroxy acetophenone as a raw material, and completes the total synthesis of the compound safloneoside through seven steps of reactions. The total synthesis method has the advantages of easily available raw materials, stable intermediates, easy control of reaction and important reference and practical values for preparing the compound saffloneoside in large quantities.
Specifically, the synthesis method of the natural product with the activity of resisting cerebral ischemia injury is characterized by preparing a natural product, namely, safloneoside according to the following synthesis route, and comprises the following steps of:
Figure BDA0001985843890000021
(1) Synthesis of Compound 3:
dissolving the compound 2 in anhydrous acetone, adding anhydrous potassium carbonate and methyl iodide under ice bath condition, stirring for reacting for 5-10 hours in ice bath, filtering to remove potassium carbonate, regulating pH of filtrate to neutrality by dilute hydrochloric acid, adding proper amount of water, extracting by ethyl acetate, mixing organic phases, drying by anhydrous sodium sulfate, filtering to remove desiccant, concentrating under reduced pressure, and performing silica gel column chromatography to obtain 3-methyl-2, 4, 6-trihydroxyacetophenone;
(2) Synthesis of Compound 5:
dissolving the compound 4 in acetic anhydride, slowly adding pyridine at room temperature, stirring at room temperature for reaction for 12-24 hours, adding methanol for quenching reaction, concentrating under reduced pressure to obtain crude product, and performing silica gel column chromatography to obtain 1-acetyl-2, 3,4, 6-tetrabenzyl glucose;
(3) Synthesis of Compound 6:
adding 1, 2-dichloroethane into the compound 3 and the compound 5, adding trifluoromethanesulfonic acid kang, stirring for reacting for 8-15 hours, quenching with saturated sodium bicarbonate, extracting with ethyl acetate, combining organic phases, washing with saturated NaCl, removing water with anhydrous sodium sulfate, concentrating under reduced pressure to obtain a crude product, and performing silica gel column chromatography to obtain 3-methyl-5- (2, 3,4, 6-tetrabenzyl glucosyl) -2,4, 6-trihydroxyacetophenone carbon glycoside;
(4) Synthesis of Compound 7:
dissolving a compound 6 in methanol, adding pyridine with the same volume as the methanol, reacting for 12-24 hours at room temperature under the condition of opening, concentrating under reduced pressure, and performing silica gel column chromatography to obtain 3-methyl-5- (2, 3,4, 6-tetrabenzyl glucosyl) -2,4, 6-trihydroxy quinoid acetophenone carbon glycoside;
(5) Synthesis of Compound 8:
dissolving a compound 7 in ethanol, adding an NaOH aqueous solution, heating and stirring to react for 4-8 hours, neutralizing a reaction solution with dilute hydrochloric acid, extracting with ethyl acetate, mixing organic phases, washing with saturated NaCl, drying with anhydrous sodium sulfate, concentrating the organic phases under reduced pressure, and performing silica gel column chromatography to obtain 2-acetyl-3, 4-dihydroxy-5- (2, 3,4, 6-tetrabenzyl glucose) cyclopentenone;
(6) Synthesis of Compound 9
Dissolving a compound 8 in absolute methanol, adding p-hydroxybenzaldehyde, adding triethylamine and L-proline, sealing at room temperature for reacting for 1-3 days, concentrating under reduced pressure, dissolving in methanol again, carrying out reflux reaction, concentrating under pressure to obtain a crude reaction solution, and purifying with Sephadex LH-20 to obtain 2-p-hydroxycinnamoyl-3, 4-dihydroxy-5- (2, 3,4, 6-tetrabenzyl glucosyl) cyclopentenone;
(7) Synthesis of Saffloneoside
Dissolving the compound 9 in anhydrous dichloromethane, cooling to below 0 ℃, dropwise adding BBr3 dissolved in the anhydrous dichloromethane, reacting for 1-25 hours at low temperature, adding water for quenching reaction, and directly purifying the water phase by using sephadex LH-20 to obtain the saffloneoside.
Wherein the compound 2 of step (1): anhydrous potassium carbonate: the molar ratio of methyl iodide is 1:5 to 7:3 to 5; the eluent used in the silica gel column chromatography is n-hexane/isopropanol, and the optimal volume ratio is 15:1.
wherein the eluent used in the silica gel column chromatography in the step (2) is petroleum ether/ethyl acetate, and the optimal volume ratio is 5:1.
wherein step (3) the compound 3: compound 5: the molar ratio of scandium triflate is 1:1 to 3:0.4 to 1; the eluent used in the silica gel column chromatography is petroleum ether/ethyl acetate, and the optimal volume ratio is 10:1.
wherein the volume ratio of the methanol to the pyridine in the step (4) is 1:1, a step of; the eluent used in the silica gel column chromatography is toluene/ethyl acetate/acetic acid, and the optimal volume ratio is 7:2:0.5.
wherein the concentration of the sodium hydroxide aqueous solution in the step (5) is 1-3 mol/L, and the reaction temperature is 50-65 ℃; the eluent used in the silica gel column chromatography is toluene/ethyl acetate/acetic acid, and the optimal volume ratio is 9:2:0.5.
wherein step (6) the compound 8: p-hydroxybenzaldehyde: l-proline: the molar ratio of triethylamine is 1: 1-2: 1 to 5:2 to 10; the eluent used by the sephadex LH-20 is methylene dichloride/methanol, and the optimal volume ratio is 2:1.
wherein the reaction temperature in the step (7) is-40-0 ℃; compound 9: the molar ratio of boron tribromide is 1:5 to 10; the eluent used by the sephadex LH-20 is water.
Detailed Description
The invention will be further understood by the following examples, which are not meant to be limiting in any way.
Example 1 synthetic preparation of safloneoside:
step 1 Synthesis of Compound 3
Compound 2 (5.0, 26.9 mmol) was dissolved in anhydrous acetone (80 mL), and anhydrous potassium carbonate (10.3, 74.6 mmol) was added under ice-bath conditions; after stirring for 15 minutes, methyl iodide (7.5 mL,107.6 mmol) was further added to the reaction mixture. After stirring and reacting for 10 hours in ice bath, filtering to remove potassium carbonate, regulating the pH of the filtrate to be neutral by dilute hydrochloric acid, adding proper amount of water, extracting with ethyl acetate for 3 times, combining organic phases, drying by anhydrous sodium sulfate, filtering to remove a drying agent, performing silica gel column chromatography, eluting with an eluent: n-hexane/isopropanol=15: 1, 2.8g of 3-methyl-2, 4, 6-trihydroxyacetophenone is obtained, and the yield is 52%; the process is as follows:
Figure BDA0001985843890000041
the structural characterization data of the product are: IR (KBr): 3200,2935,1630,1569,1443,1361,1113,796cm -1 ； 1 H NMR(500MHz,DMSO-d 6 ):δ13.97(s,1H),10.55(s,1H),10.32(s,1H),6.01(s,1H),2.55(s,3H),1.83(s,3H)ppm； 13 C NMR(500MHz,DMSO-d 6 ):δ203.1,164.0,163.3,160.7,104.4,101.9,94.5,33.1,7.9ppm.High Resolution MS(ESI):Calculated for C 9 H 9 O 4 [M-H] - :181.0579,Found:181.0504.
Step 2 Synthesis of Compound 5
Dissolving compound 4 (30.0 g,55.6 mmol) in acetic anhydride (50 mL), slowly adding pyridine (150 mL) at room temperature, stirring at room temperature for reaction for 12 hours, adding methanol for quenching reaction, concentrating under reduced pressure to obtain crude product, performing silica gel column chromatography, and performing petroleum ether/ethyl acetate=5:1 to obtain 32.4g of 1-acetyl-2, 3,4, 6-tetrabenzyl glucose with yield of 98%; the process is as follows:
Figure BDA0001985843890000042
step 3 Synthesis of Compound 6
Compound 3 (2.5 g,13.7 mmol) and compound 5 (23.9 g,41.1 mmol) were taken, 1, 2-dichloroethane (120 mL) was added, and then kang triflate (2.7 g,5.5 mmol) was added, the reaction was quenched at 45 ℃ for 10 hours, saturated sodium bicarbonate (150 mL) was quenched, extracted three times with ethyl acetate, 250mL each time, the organic phases were combined, washed with saturated NaCl, dried over anhydrous sodium sulfate, concentrated under reduced pressure to give crude product, silica gel column chromatography, eluent: petroleum ether/ethyl acetate = 10:1, 9.0g of 3-methyl-5- (2, 3,4, 6-tetrabenzyl glucosyl) -2,4, 6-trihydroxy acetophenone carbon glycoside is obtained, and the yield is 95%; the process is as follows:
Figure BDA0001985843890000043
the structural characterization data of the product are: IR (KBr) 3294,2916,2880,1621,1593,1088,751,694cm -1 ； 1 H NMR(500MHz,DMSO-d 6 ):δ7.43-7.03(20H),5.14-4.57(8H),4.18(d,J＝10.3Hz,1H),3.93-3.83(m,3H),3.79-3.74(m,3H),2.59(s,3H),2.04(s,3H)； 13 C NMR(500MHz,DMSO-d 6 ):δ204.5,159.7,139.9,139.4,138.5,129.2-128.2(20C),106.3,104.3,103.3,86.8,82.2,79.4,78.1,76.0,75.9,75.6,75.5,73.7,68.7,33.3,7.8ppm.High Resolution MS(ESI):Calculated for C 43 H 43 O 9 [M-H] - :703.2985,Found:703.2916.
Step 4 Synthesis of Compound 7
Compound 6 (3.0 g,4.5 mmol) was dissolved in methanol (30 mL), pyridine (30 mL) was added in the same volume as methanol, and reacted at room temperature for 24 hours under open condition, concentrated under reduced pressure, silica gel column chromatography, eluent: toluene/ethyl acetate/acetic acid = 7:2:0.5 g of 3-methyl-5- (2, 3,4, 6-tetrabenzyl glucose group) -3,4, 6-trihydroxy quinoid acetophenone carbon glycoside with the yield of 82 percent; the process is as follows:
Figure BDA0001985843890000051
the structural characterization data of the product are: IR (KBr): 3368,2924,2867,1623,1537,1455,1070,737,698cm -1 . 1 H NMR(500MHz,DMSO-d 6 ):δ17.77(s,1H),17.70(s,1H),7.33-7.17(m,40H),4.80-4.72(6H),4.61-4.50(10H),3.60-3.34(14H),2.34(6H),1.21(s,3H),1.17(3H). 13 C NMR(500MHz,DMSO-d 6 ):δ197.5,196.8,196.1(2C),193.9(2C),172.7(2C),139.5-138.9(8C),135.3(2C),102.0(2C),87.5,87.4,79.5-78.6(8C),75.1-71.9(10C),69.7(2C),29.7,29.2,27.8,27.5ppm.High Resolution MS(ESI):Calculated for C 43 H 45 O 10 [M+H] + :721.2934,Found:721.3003.
Step 5 Synthesis of Compound 8
Compound 7 (2.0 g,2.9 mmol) was taken and dissolved in ethanol (20 mL), then 2M NaOH aqueous solution (20 mL) was added in the same volume as ethanol and reacted at 50 ℃ for 6 hours, 1M diluted hydrochloric acid was used to neutralize the reaction solution, ethyl acetate was extracted 3 times, 100mL each time, the organic phases were combined, saturated NaCl water-washed, dried over anhydrous sodium sulfate, the organic phases were concentrated under reduced pressure, silica gel column chromatography, eluent: toluene/ethyl acetate/acetic acid = 9:2:0.5 to obtain 1.0g of 2-acetyl-3, 4-dihydroxy-5- (2, 3,4, 6-tetrabenzyl glucose group) cyclopentenone with a yield of 52%; the process is as follows:
Figure BDA0001985843890000052
the structural characterization data of the product are: [ alpha ]] 20 D ＝+25.8(c＝0.17,MeOH)；IR(KBr):3406,2917,2869,1596,1455,1095,736,698cm -1 ； 1 H NMR(500MHz,DMSO-d 6 )δ7.33-7.17(20H),5.89-5.81(OH),4.84-4.70(5H),4.54-4.42(3H),4.35(m,1H),3.90(d,J＝9.3Hz,1H),3.70-3.44(6H),2.63(m,1H),2.29(s,3H)； 13 C NMR(500MHz,DMSO-d 6 ) Delta 202.5,201.8,192.3,139.3,139.1,139.0,138.8,129.0-128.0 (20C), 112.5,87.2,80.5,80.0,78.8,76.6,75.2,74.8,74.7,72.6,70.8,69.0,53.5,28.2 step 6 Synthesis of Compound 9
Dissolving compound 8 (0.8 g,1.2 mmol) in anhydrous methanol (10 mL), adding p-hydroxybenzaldehyde (220 mg,1.8 mmol), adding triethylamine (4816 mg,4.8 mmol) and L-proline (276 mg,2.4 mmol), sealing at room temperature, reacting for 3 days, concentrating under reduced pressure, redissolving in methanol, refluxing for 8 hours, concentrating under pressure to obtain crude reaction liquid, purifying sephadex LH-20 (MeOH: H2O=20:80), and obtaining 580mg of 2-p-hydroxycinnamoyl-3, 4-dihydroxy-5- (2, 3,4, 6-tetrabenzyl glucose) cyclopentenone with the yield of 64%; the process is as follows:
Figure BDA0001985843890000061
the structural characterization data of the product are: [ alpha ]] 20 D ＝-18.2(c＝0.10,MeOH)；IR(KBr):3286,2903,1578,1396,1283,1097,982,738,698cm -1 ； 1 H NMR(500MHz,DMSO-d 6 ):δ10.47(OH,s),7.98(1H,d,J＝15.3Hz),7.74(1H,d,J＝15.3Hz),7.66(2H,d,J＝8.4Hz),7.35-7.20(20H),6.89(2H,d,J＝8.4Hz),4.87(2H,m),4.80(2H,dd,J＝4.2,8.6Hz),4.79(1H,m),4.56(2H,d,J＝10.9Hz),4.41(2H,q,J＝6.3,),3.99(1H,d,J＝9.9),3.77(1H,t,J＝8.9),3.60-3.48(5H),2.96(1H,m)； 13 C NMR(500MHz,DMSO-d 6 ):202.5,201.4,187.6,162.2,144.2,139.3,139.0,139.0,138.8,132.4(2C),129.0-127.9(20C),126.1,117.0(2C),110.8,87.0,79.8,78.9,78.8,75.6,75.3,74.1,74.7,72.5,70.1,69.0,54.1.High Resolution MS(ESI):Calculated for C 48 H 47 O 10 [M+H] + :783.3125,Found:783.3122.
Step 7, synthesizing the safloneoside
Dissolving compound 9 (500 mg,0.64 mmol) in anhydrous dichloromethane (10 mL), cooling to-40deg.C, and dropwise adding BBr dissolved in anhydrous dichloromethane (5 mL) 3 (1.6 g,6.4 mmol), reacting for 2 hours at 40 ℃, adding a proper amount of water for quenching reaction, directly purifying the water phase by using sephadex LH-20, and obtaining 311mg of safloneoside with the yield of 100%, wherein the following reaction is carried out:
Figure BDA0001985843890000062
the structural characterization data of the product are: [ alpha ]] 20 D -30.5(c 0.15,MeOH)；HR-ESI-MS m/z 423.1284[M+H] + (calcd for C 20 H 23 O 10 ,423.1247)；ECD(CH 3 OH)Δε278(-2.58),250(+7.72)nm；IR(KBr)3332,2923,2862,1684,1621,1578,1399,1093cm -1 ； 1 H NMR(500MHz,D 2 O-NaOD)δ H :7.42(1H,d,J＝15.8Hz,7-H),7.34(1H,d,J＝8.5Hz,10-H),7.34(1H,d,t,J＝8.5Hz,10-H and 14-H),7.32(1H,t,J＝15.8Hz,8-H),6.51(1H,d,J＝8.5Hz,10-H),4.33(1H,d,J＝4.5Hz,4-H),3.77(1H,dd,J＝8.5,2.0Hz,1′-H),3.65(1H,m,6′-H 1 ),3.50(1H,dd,J＝12.5,5.0Hz,6′-H 2 ),3.41(1H,m,3′-H),3.40(1H,m,4′-H),3.24(1H,m,2′-H),3.23(1H,m,5′-H),2.74(1H,brs,5-H)； 13 C NMR(500MHz,D 2 O-NaOD)δ C :202.6(C-3),201.2(C-1),188.8(C-6),170.8(C-12),144.3(C-8),131.2(C-10,14),121.2(C-9),119.6(C-11,13),119.4(C-7),114.5(C-2),79.4(C-5′),77.7(C-3′),76.0(C-1′),71.0(C-4′),70.2(C-4),69.6(C-2′),60.8(C-6′),53.0(C-5).

Claims (9)

1. The synthesis method of the natural product safflower neoglycoside as shown in formula 1 is characterized by comprising the following synthesis steps:
2,4, 6-trihydroxy acetophenone is taken as a raw material, and a compound, namely, safloneoside is synthesized according to the following synthesis route;
Figure FDA0004133726550000011
wherein Bn is benzyl and Ac is acetyl.
2. The synthetic method according to claim 1, characterized in that the compound safloneoside is prepared by the steps of:
(1) Synthesis of Compound 3:
dissolving the compound 2 in anhydrous acetone, adding anhydrous potassium carbonate and methyl iodide under ice bath condition, stirring for reacting for 5-10 hours in ice bath, filtering to remove potassium carbonate, regulating pH of filtrate to neutrality by dilute hydrochloric acid, adding proper amount of water, extracting by ethyl acetate, mixing organic phases, drying by anhydrous sodium sulfate, filtering to remove desiccant, concentrating under reduced pressure, and performing silica gel column chromatography to obtain 3-methyl-2, 4, 6-trihydroxyacetophenone;
(2) Synthesis of Compound 5:
dissolving the compound 4 in acetic anhydride, slowly adding pyridine at room temperature, stirring at room temperature for reaction for 12-24 hours, adding methanol for quenching reaction, concentrating under reduced pressure to obtain crude product, and performing silica gel column chromatography to obtain 1-acetyl-2, 3,4, 6-tetrabenzyl glucose;
(3) Synthesis of Compound 6:
adding 1, 2-dichloroethane into the compound 3 and the compound 5, adding scandium triflate, stirring and reacting for 8-15 hours, quenching by saturated sodium bicarbonate, extracting by ethyl acetate, merging organic phases, washing by saturated NaCl, removing water by anhydrous sodium sulfate, concentrating under reduced pressure to obtain a crude product, and performing silica gel column chromatography to obtain 3-methyl-5- (2, 3,4, 6-tetrabenzyl glucosyl) -2,4, 6-trihydroxyacetophenone carbon glycoside;
(4) Synthesis of Compound 7:
dissolving a compound 6 in methanol, adding pyridine, reacting for 12-24 hours at room temperature under an open condition, concentrating under reduced pressure, and performing silica gel column chromatography to obtain 3-methyl-5- (2, 3,4, 6-tetrabenzyl glucosyl) -2,4, 6-trihydroxy quinoid acetophenone carbon glycoside;
(5) Synthesis of Compound 8:
dissolving a compound 7 in ethanol, adding an NaOH aqueous solution, heating and stirring to react for 4-8 hours, neutralizing a reaction solution with dilute hydrochloric acid, extracting with ethyl acetate, mixing organic phases, washing with saturated NaCl, drying with anhydrous sodium sulfate, concentrating the organic phases under reduced pressure, and performing silica gel column chromatography to obtain 2-acetyl-3, 4-dihydroxy-5- (2, 3,4, 6-tetrabenzyl glucose) cyclopentenone;
(6) Synthesis of Compound 9
Dissolving a compound 8 in absolute methanol, adding p-hydroxybenzaldehyde, adding triethylamine and L-proline, sealing at room temperature for reacting for 1-3 days, concentrating under reduced pressure, dissolving in methanol again, carrying out reflux reaction, concentrating under pressure to obtain a crude reaction solution, and purifying with Sephadex LH-20 to obtain 2-p-hydroxycinnamoyl-3, 4-dihydroxy-5- (2, 3,4, 6-tetrabenzyl glucosyl) cyclopentenone;
(7) Synthesis of Saffloneoside
Dissolving the compound 9 in anhydrous dichloromethane, dropwise adding BBr3 dissolved in the anhydrous dichloromethane under ice bath condition, reacting for 1-5 hours at low temperature, adding water for quenching reaction, and directly purifying the water phase by using sephadex LH-20 to obtain the saffloneoside.
3. The method for synthesizing the natural product safloneoside according to claim 2, wherein: compound 2 of step (1): anhydrous potassium carbonate: the molar ratio of methyl iodide is 1:5 to 7:3 to 5; the eluent used in the silica gel column chromatography is n-hexane/isopropanol, and the volume ratio of n-hexane/isopropanol is 15:1.
4. the method for synthesizing the natural product safloneoside according to claim 2, wherein: the eluent used in the silica gel column chromatography in the step (2) is petroleum ether/ethyl acetate, and the volume ratio of petroleum ether/ethyl acetate is 5:1.
5. the method for synthesizing the natural product safloneoside according to claim 2, wherein: step (3) the compound 3: compound 5: the molar ratio of scandium triflate is 1:1 to 3:0.4 to 1; the eluent used in the silica gel column chromatography is petroleum ether/ethyl acetate, and the volume ratio of petroleum ether/ethyl acetate is 10:1.
6. the method for synthesizing the natural product safloneoside according to claim 2, wherein: the volume ratio of the methanol to the pyridine in the step (4) is 1:0.5 to 1; the eluent used in the silica gel column chromatography is toluene/ethyl acetate/acetic acid, and the volume ratio of toluene/ethyl acetate/acetic acid is 7:2:0.5.
7. the method for synthesizing the natural product safloneoside according to claim 2, wherein: the concentration of the sodium hydroxide aqueous solution in the step (5) is 1-3 mol/L, and the reaction temperature is 50-65 ℃; the eluent used in the silica gel column chromatography is toluene/ethyl acetate/acetic acid, and the volume ratio of toluene/ethyl acetate/acetic acid is 9:2:0.5.
8. the method for synthesizing the natural product safloneoside according to claim 2, wherein: compound 8 of step (6): p-hydroxybenzaldehyde: l-proline: the molar ratio of triethylamine is 1: 1-2: 1 to 5:2 to 10; the eluent used by the sephadex LH-20 is methylene dichloride/methanol, and the volume ratio of the methylene dichloride to the methanol is 2:1.
9. the method for synthesizing the natural product safloneoside according to claim 2, wherein: the reaction temperature in the step (7) is-40-0 ℃; compound 9: the molar ratio of boron tribromide is 1:5 to 10; the eluent used by the sephadex LH-20 is water.
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