CN112390834B - Chitosan oligosaccharide-g-citronellol derivative and preparation method thereof - Google Patents
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Abstract
The invention discloses a chitosan oligosaccharide-g-citronellol derivative and a preparation method thereof. The invention makes citronellol group with good anti-inflammatory activity connected to the reactive active site of chitosan oligosaccharide to enhance the anti-inflammatory activity of chitosan oligosaccharide and the water solubility of citronellol, thus obtaining the chitosan oligosaccharide-g-citronellol derivative. The invention has simple preparation process, low cost, simple purification method and stable property, and the obtained chitosan oligosaccharide derivative has good water solubility, thermal stability and anti-inflammatory activity, has good inhibitory activity on the swelling degree of feet of a rat induced by carrageenan, and has wide application prospect in the fields of medicine, agriculture, food, cosmetics and the like.
Description
Technical Field
The invention relates to a chitosan oligosaccharide-g-citronellol derivative and a preparation method thereof, belonging to the technical field of anti-inflammatory agents.
Background
In modern life, people are stimulated by factors such as living and working pressure, unhealthy diet, viruses, bacteria, tissue damage, necrosis and the like, acute inflammation is easy to occur, and if the treatment is not carried out in time, the chronic inflammation stage can be entered. Many diseases such as diabetes and arthritis, or cancer are accompanied by inflammatory reactions, and therefore, it is important to control and treat inflammation. The traditional anti-inflammatory drugs have obvious effect on inhibiting inflammation, but have some adverse reactions which can cause harm to human bodies. Natural compounds such as chitosan oligosaccharide and citronellol are favored by people due to the characteristics of safety, no toxicity, good thermal stability, good biological activity and the like, and the development of natural anti-inflammatory agents with stronger anti-inflammatory activity through chemical modification has become a hotspot of research.
Citronellol (3, 7-dimethyl-6-octen-1-ol) is an acyclic monoterpene enol, has two optical isomers of levorotation and dextrorotation, is naturally present in plant essential oil, has a fragrance similar to that of rose flowers, is a main component of essence and spice, has activities of oxidation resistance, inflammation resistance, bacteria resistance, tumor resistance, organism immunity improvement and the like, and is widely applied to the fields of medicines, tobacco, food ingredients and the like. However, the disadvantage of water insolubility of citronellol limits the application thereof, so that it is urgently required to overcome the disadvantage so as to widely apply citronellol to the fields of medicine, food and the like.
The chitosan oligosaccharide is low molecular weight basic amino oligosaccharide with polymerization degree of 2-20 obtained by degrading and breaking chitosan main chain physically, chemically or enzymatically. Has no biological toxicity, natural degradability, biocompatibility and chemical reactivity, and is often used as an antioxidant and a natural antibacterial agent in the food industry. In addition, the chitosan oligosaccharide has stronger biological functional characteristics of anti-inflammatory activity, tumor growth inhibition, immunoregulation, being used as a carrier for gene delivery, a hemostatic agent for wound dressing and the like, so that the chitosan oligosaccharide can be developed as a potential anti-inflammatory agent. However, since chitosan oligosaccharide is a natural macromolecular product, when used as an anti-inflammatory agent, it still has the disadvantages of low anti-inflammatory activity, etc., compared to the conventional common anti-inflammatory drugs, so that research on the anti-inflammatory activity thereof is very limited at present.
Disclosure of Invention
In order to solve the technical problems, the invention provides a chitosan oligosaccharide-g-citronellol derivative and a preparation method thereof, wherein a citronellol group with good anti-inflammatory activity is grafted onto a reactive active site of chitosan oligosaccharide to enhance the anti-inflammatory activity of the chitosan oligosaccharide and the water solubility of citronellol, so that the chitosan oligosaccharide derivative with good water solubility and thermal stability is obtained.
The first purpose of the invention is to provide a chitosan oligosaccharide-g-citronellol derivative, which is shown in a formula (1):
wherein n is 2-20.
The second purpose of the invention is to provide a preparation method of the chitosan oligosaccharide-g-citronellol derivative, which comprises the following steps:
and (2) dropwise adding the citronellyl bromine solution into the chitosan oligosaccharide solution in the presence of a catalyst to react, and collecting a product after the reaction is finished to obtain the chitosan oligosaccharide-g-citronellol derivative.
Furthermore, the molecular weight of the chitosan oligosaccharide is less than or equal to 2000Da, and the deacetylation degree is 80-95%.
Further, the mass-volume ratio of the chitosan oligosaccharide to the citronellyl bromide is 1:2-1:6(g: mL).
The invention mainly adjusts the substitution degree of the chitosan oligosaccharide-g-citronellol derivative by changing the proportion of the chitosan oligosaccharide and citronellol, and synthesizes the chitosan oligosaccharide-g-citronellol derivative with the substitution degree of 0.16-0.20 within the mass-volume ratio of the chitosan oligosaccharide to citronellyl bromide of 1:2-1:6(g: mL), and the yield is 60% -80%. More preferably, the chitosan oligosaccharide-g-citronellol derivative with the substitution degree of 0.19-0.20 is synthesized when the mass-volume ratio of the chitosan oligosaccharide to the citronellyl bromide is 1:3-5(g: mL), and has better anti-inflammatory activity.
Further, the catalyst is triethylamine, pyridine or ethylenediamine.
Furthermore, the addition amount of the catalyst is 1-5ml of catalyst per gram of chitosan oligosaccharide.
Further, the reaction temperature is 45-50 ℃, and the reaction time is 6-10 h.
Further, the method also comprises a step of terminating the reaction by using an excessive amount of organic solvent after the reaction is finished.
Further, the organic solvent is acetone.
Further, the collecting the product comprises the following steps: and after the reaction is finished, centrifuging, collecting precipitate, extracting by adopting an organic solvent, drying in vacuum to obtain solid powder, dialyzing the solid powder, and freeze-drying to obtain the chitosan oligosaccharide-g-citronellol derivative.
Further, the organic solvent is ethanol, diethyl ether, petroleum ether or acetone.
Further, the dialysis is carried out for 12-36h by adopting a dialysis bag with the molecular weight cut-off of 77-100 Da.
Further, the citronellyl bromide is prepared by the following method: slowly dripping a phosphorus tribromide solution into a citronella alcohol solution containing a catalyst according to the volume ratio of 5:2-4, and stirring and reacting for 45-120min under the condition of an ice salt bath; after the reaction is finished, sequentially washing the mixture for 3 to 5 times by using 4 to 6 percent sodium bicarbonate solution, deionized water and saturated saline solution, adding anhydrous magnesium sulfate, drying, filtering, and performing rotary evaporation and concentration to obtain light yellow oily liquid citronellyl bromide; wherein the catalyst is triethylamine, pyridine or ethylenediamine.
The third purpose of the invention is to provide the application of the chitosan oligosaccharide-g-citronellol derivative in medicine, agriculture, food and cosmetics.
The invention has the beneficial effects that:
the invention makes citronellol group with good anti-inflammatory activity connected to the reactive active site of chitosan oligosaccharide to enhance the anti-inflammatory activity of chitosan oligosaccharide and the water solubility of citronellol, thus obtaining the chitosan oligosaccharide-g-citronellol derivative. The invention has simple preparation process, low cost, simple purification method and stable property, and the obtained chitosan oligosaccharide derivative has good water solubility, thermal stability and anti-inflammatory activity, has good inhibitory activity on the swelling degree of feet of a rat induced by carrageenan, and has wide application prospect in the fields of medicine, agriculture, food, cosmetics and the like.
Drawings
FIG. 1 is a scheme of the synthesis of the chitosan oligosaccharide-g-citronellol derivative;
FIG. 2 is an infrared spectrum of a chitosan oligosaccharide of the present invention;
FIG. 3 is an infrared spectrum of a chitooligosaccharide-g-citronellol derivative of the present invention;
FIG. 4 shows the results of the present invention for chitooligosaccharide (a), citronellol (b), and chitooligosaccharide-g-citronellol derivative (c)1H-NMR chart;
FIG. 5 is a Thermogram (TGA) of the thermo-gravimetric rate of the chitosan oligosaccharide, chitosan oligosaccharide-g-citronellol derivative of the present invention;
FIG. 6 is a first derivative graph (DTG) of a thermogram of chitosan oligosaccharide, chitosan oligosaccharide-g-citronellol derivative of the present invention.
Detailed Description
The present invention is further described below in conjunction with the following figures and specific examples so that those skilled in the art may better understand the present invention and practice it, but the examples are not intended to limit the present invention.
Example 1: preparation of chitosan oligosaccharide-g-citronellol derivative
1. Preparation of citronellyl bromide
Dissolving 5mL of citronellol and 2mL of phosphorus tribromide with 30mL of anhydrous ether respectively, adding a chitosan oligosaccharide solution and 0.45mL of pyridine into a three-neck flask, quickly stirring under the condition of ice salt bath, slowly dropwise adding the phosphorus tribromide solution into the reaction system, continuously and quickly stirring for 45min after dropwise adding is finished, washing with a 5% sodium bicarbonate solution, deionized water and saturated salt solution for 3 times in sequence, adding anhydrous magnesium sulfate, drying, filtering with a 0.22-micron filter membrane, and rotationally evaporating and concentrating for 30min at 35 ℃ to obtain the light yellow oily liquid citronellyl bromide.
2. Preparation of chitosan oligosaccharide-g-citronellol derivative
Dissolving 1g of chitosan oligosaccharide and 2mL of citronellyl bromide by using dimethyl sulfoxide and dimethyl formamide respectively, adding triethylamine as a catalyst, slowly adding citronellyl bromide solution into the chitosan oligosaccharide solution by using a constant-pressure funnel, reacting at 45 ℃ for 6 hours, adding excessive acetone after the reaction is finished, stopping the reaction, centrifuging and collecting precipitates. Extracting with petroleum ether in a Soxhlet extraction device for 12h, vacuum drying to obtain brown solid powder, dialyzing the powder in a dialysis bag with molecular weight cutoff of 77-100Da for 12h, and freeze drying to obtain the chitosan oligosaccharide-g-citronellol derivative.
The substitution degree of the chitosan oligosaccharide-g-citronellol derivative is 0.165, the yield is 60%, and the chitosan oligosaccharide-g-citronellol derivative is characterized by infrared spectroscopy, nuclear magnetic resonance and thermogravimetric analysis.
FIG. 2 is a drawing showing the preparation of chitooligosaccharides in this exampleInfra-red spectrum of 3400.56cm-1Is the stretching vibration absorption peak of O-H and N-H, 2920.78cm-1The absorption peak of C-H stretching vibration is 1620.59cm-1Is NH2Has a bending vibration absorption peak of 1155.97cm-1And 1071.52cm-1The absorption peak of C-O stretching vibration is 893.24cm-1Is a ring expansion vibration absorption peak.
FIG. 3 is an infrared spectrum of a chitooligosaccharide-g-citronellol derivative of this example, in which 1620cm is shown-1The obvious double bond absorption peak is caused by the coincidence of the C ═ C absorption peak in citronellol and the C ═ O absorption peak in chitosan oligosaccharide; 1520cm-1The absorption peak of the amino group is weakened; 2920cm-1The absorption peak of methyl group at (1) is enhanced, 3400cm-1The absorption peak width of the derivative is reduced and the intensity is weakened, which shows that the chitosan oligosaccharide-g-citronellol derivative is successfully synthesized, and the alkylation reaction simultaneously occurs in-OH and-NH of the chitosan oligosaccharide2The above.
FIG. 4 a is the chitosan oligosaccharide of this example1H NMR chart, peaks at 2.05-2.25ppm of chemical shift corresponding to-CH on acetamido residue3A proton peak of (a); the peak at which the chemical shift occurred at 3.19ppm corresponded to H on the glucosamine and acetamido residues of the chitosan oligosaccharide2A proton peak of (a); chemical shift chemical shifts occur at multiplets of 3.21-3.92ppm are methine hydrogens on glucosamine and acetylglucosamine.
FIG. 4c shows the preparation of the chitooligosaccharide-g-citronellol derivative of this example1H NMR chart, chemical shift occurring at 0.90ppm proton peak assignable to H-10 on 3, 7-dimethyl-6-octen-1-ol backbone; 1.20-1.69ppm can be assigned as proton peak at H-3, H-4, H-5, H-9 on 3, 7-dimethyl-6-octen-1-ol skeleton; 2.06ppm was assigned as the proton peak at H-2 on the 3, 7-dimethyl-6-octen-1-ol backbone; 3.63ppm was assigned as the proton peak at H-1 on the 3, 7-dimethyl-6-octen-1-ol backbone; 5.08-5.34ppm can be assigned as the proton peak at H-6 on the 3, 7-dimethyl-6-octen-1-ol backbone. Therefore, the attribution of the chemical shifts proves that the citronellol and the chitosan oligosaccharide have alkylation reaction, and the chitosan oligosaccharide-g-citronellol derivative is successfully prepared.
Example 2: preparation of chitosan oligosaccharide-g-citronellol derivative
1. Preparation of citronellyl bromide
Dissolving 5mL of citronellol and 3mL of phosphorus tribromide with 40mL of anhydrous ether respectively, adding a chitosan oligosaccharide solution and 0.5mL of pyridine into a three-neck flask, quickly stirring under the condition of ice salt bath, dropwise adding a phosphorus tribromide solution into the reaction system, continuously and quickly stirring for 90min after dropwise adding is finished, washing with a 5% sodium bicarbonate solution, deionized water and saturated saline water for 4 times in sequence, adding anhydrous magnesium sulfate, drying, filtering with a 0.22-micron filter membrane, and rotationally evaporating and concentrating for 40min at 40 ℃ to obtain the light yellow oily liquid citronellyl bromide.
2. Preparation of chitosan oligosaccharide-g-citronellol derivative
Dissolving 1g of chitosan oligosaccharide and 4mL of citronellyl bromide by using dimethyl sulfoxide and dimethyl formamide respectively, adding triethylamine as a catalyst, slowly adding a citronellyl bromide solution into the chitosan oligosaccharide solution by using a constant-pressure funnel, reacting for 8 hours at 45 ℃, adding excessive acetone to terminate the reaction after the reaction is finished, and centrifuging and collecting precipitates. Extracting with petroleum ether in a Soxhlet extraction device for 12h, vacuum drying to obtain brown solid powder, dialyzing the powder in a dialysis bag with molecular weight cutoff of 77-100Da for 24h, and freeze drying to obtain the chitosan oligosaccharide-g-citronellol derivative. The substitution degree of the chitosan oligosaccharide-g-citronellol derivative is 0.199, and the yield is 80%.
Example 3: preparation of chitosan oligosaccharide-g-citronellol derivative
1. Preparation of citronellyl bromide
Dissolving 5mL of citronellol and 4mL of phosphorus tribromide with 50mL of anhydrous ether respectively, adding a chitosan oligosaccharide solution and 0.55mL of pyridine into a three-neck flask, quickly stirring under the condition of an ice salt bath, dropwise adding the phosphorus tribromide solution into the reaction system, continuously and quickly stirring for 120min after dropwise adding is finished, washing with a 5% sodium bicarbonate solution, deionized water and saturated salt solution for 5 times in sequence, adding anhydrous magnesium sulfate, drying, filtering with a 0.22-micron filter membrane, and rotationally evaporating and concentrating for 45min at 50 ℃ to obtain the light yellow oily liquid citronellyl bromide.
2. Preparation of chitosan oligosaccharide-g-citronellol derivative
Dissolving 1g of chitosan oligosaccharide and 6mL of citronellyl bromide by using dimethyl sulfoxide and dimethyl formamide respectively, adding triethylamine as a catalyst, slowly adding the chitosan oligosaccharide solution into the citronellyl bromide solution by using a constant-pressure funnel, reacting at 50 ℃ for 10 hours, adding excessive acetone after the reaction is finished, stopping the reaction, centrifuging and collecting precipitates. Extracting with petroleum ether in a Soxhlet extraction device for 12h, vacuum drying to obtain brown solid powder, dialyzing the powder in a dialysis bag with molecular weight cutoff of 77-100Da for 24h, and freeze drying to obtain the chitosan oligosaccharide-g-citronellol derivative. The substitution degree of the chitosan oligosaccharide-g-citronellol derivative is 0.172, and the yield is 70%.
Example 4: thermal stability test
The thermal stability was determined by a thermal analyzer of the Mettler-Torledo instruments Ltd. The detection conditions are that the heating rate is 20 ℃/min, N2The flow rate is 40mL/min, and the heating temperature range is 30-600 ℃. The Thermogram (TGA) and the first Derivative (DTG) of the thermogram of chitosan oligosaccharide and chitosan oligosaccharide-g-citronellol derivative are shown in FIG. 5 and FIG. 6. As can be seen from FIGS. 5 and 6, the weight loss of the chitosan oligosaccharide and the chitosan oligosaccharide-g-citronellol derivative gradually increases with the increase of temperature. The chitosan oligosaccharide has two weight loss stages at the temperature of 30-600 ℃, the first-order weight loss occurs at the temperature of 40-160 ℃, and the weight loss is about 8.9 percent, which is caused by the volatilization of adsorbed water, crystallized water and other micromolecular substances in a sample. The second order weight loss occurred at 180 ℃ and 300 ℃ and was about 47.06% weight loss, mainly due to decomposition of the polymer of the dehydration, depolymerization and alkylation units of the glycorings of chitosan. Wherein, TmaxAt 210 deg.c. The modified chitosan oligosaccharide-g-citronellol derivative also has two weight loss stages at 30-600 ℃, wherein the first-order weight loss occurs at 40-150 ℃, the weight loss is about 10%, the second-order weight loss occurs at 350 ℃ and the weight loss is about 41.17%, wherein T ismaxAt 250 ℃. The results of thermogravimetric experiments show that the thermal stability of the chitosan oligosaccharide-g-citronellol derivative is higher than that of the raw material chitosan oligosaccharide, so that the molecular arrangement of the chitosan oligosaccharide is changed after citronellol is introduced into the sugar chain of the chitosan oligosaccharide, the structure is more regular and consistent, and the thermal stability of the chitosan oligosaccharide-g-citronellol derivative is enhanced.
Example 5: anti-inflammatory assay
(1) Laboratory animal
SD male rats weighing 130-.
(2) Experimental procedure
The experiment adopts a carrageenan induced rat foot swelling experimental model. Animals should be acclimated for three days in the animal room prior to purchase in the animal experiment, after which the rats are randomly divided into 10 groups of 10 animals per group, namely a blank control group 1 (equal volume of distilled water), a blank control group 2 (equal volume of 0.2% Tween-80 solution), a positive control group (5mg/kg of indometacin dissolved by 0.2% Tween-80), a model group (equal volume of distilled water), a chitosan oligosaccharide group (dissolved by distilled water and 100mg/kg), citronellol group (dissolved by 0.2% Tween-80 and 100mg/kg), a chitosan oligosaccharide and citronellol compound group (100mg/kg), a COS-g-Cit1 group (dissolved by distilled water and 100mg/kg), a COS-g-Cit2 group (100mg/kg) and a COS-g-Cit3 group (100mg/kg), wherein the rats in each group are subjected to gastric lavage, and the dosage is 1mL/100g of body weight. The administration was 1 time per day for 7 consecutive days at a fixed time. 1% carrageenan (0. lmL/mouse) is injected subcutaneously into the right hind toe of each mouse 1h after the last administration to cause inflammation, after 4h, the mouse is killed by dislocation of cervical vertebra, inflammation swelling feet are cut off at a position of 0.5cm above the ankle joint, and the mouse is washed by normal saline, wiped dry, weighed, placed into a centrifuge tube and stored in a refrigerator at-80 ℃ for later use.
Swelling degree of foot (mg) ═ weight of right foot (mg) — weight of left foot (mg)
The inhibition rate is (average swelling degree of model group-average swelling degree of administration group)/average swelling degree of model group X100%
The anti-inflammatory results are shown in table 1.
TABLE 1 Effect of Chitosan oligosaccharide-citronellol derivatives on carrageenan-induced foot swelling in rats (x. + -.s)
Note: significant difference compared with the model (P < 0.05), and significant difference compared with the model (P < 0.01)
From the results in table 1, in the carrageenan-induced rat paw edema model, compared with the model group, the paw edema degree in the positive control group is significantly reduced, and the paw edema degrees of the three derivative groups with different degrees of substitution are all lower than those in the model group, and the difference is significant. In addition, the inhibition rate of the examples on the degree of foot swelling is obviously higher than that of chitosan oligosaccharide, and the differences are obvious, so the chitosan oligosaccharide can be used as a potential anti-inflammatory agent.
In summary, the principle of the present invention is as follows: the molecular structure of the chitosan oligosaccharide has three chemical reaction sites, and according to the activity of the three positions, if alkylation reaction occurs, the chemical reaction sites preferentially occur on C-2-site amino, secondly on C-6-site primary hydroxyl and finally on C-3-site secondary hydroxyl. Mainly because the electron cloud density on the amino nitrogen at the C-2 position is the largest and the nucleophilicity is the strongest, while the electron cloud density of the hydroxyl at the C-3 and C-6 positions is smaller than that of the electron cloud at the C-2 position, the nucleophilicity is weaker and the steric hindrance effect is certain. However, the invention does not carry out protection reaction on the hydroxyl at C-3 and C-6 positions of the chitosan oligosaccharide, and the infrared spectrum result also proves that citronellol is grafted to the amino group of the chitosan oligosaccharide and a small part of citronellol is grafted to the hydroxyl of the chitosan oligosaccharide.
The above-mentioned embodiments are merely preferred embodiments for fully illustrating the present invention, and the scope of the present invention is not limited thereto. The equivalent substitution or change made by the technical personnel in the technical field on the basis of the invention is all within the protection scope of the invention. The protection scope of the invention is subject to the claims.
Claims (7)
1. The application of the chitosan oligosaccharide-g-citronellol derivative in preparing the anti-inflammatory agent is characterized in that the preparation method of the chitosan oligosaccharide-g-citronellol derivative comprises the following steps:
dropwise adding a citronellyl bromine solution into a chitosan oligosaccharide solution in the presence of a catalyst to react, and collecting a product after the reaction is finished to obtain a chitosan oligosaccharide-g-citronellol derivative; the molecular weight of the chitosan oligosaccharide is less than or equal to 2000Da, and the deacetylation degree is 80-95%;
the structure of the chitosan oligosaccharide-g-citronellol derivative is shown as the following formula:
wherein n is 2-20.
2. The use of claim 1, wherein the mass to volume ratio of the chitosan oligosaccharide to the citronellyl bromide in g/mL is 1:2 to 1: 6.
3. The use according to claim 1, wherein the catalyst is triethylamine, pyridine or ethylenediamine.
4. The use according to claim 3, wherein the catalyst is added in an amount of 1-5ml per gram of chito-oligosaccharide.
5. The use according to claim 1, wherein the reaction temperature is 45-50 ℃ and the reaction time is 6-10 h.
6. The use of claim 1, wherein said collecting the product comprises the steps of: and after the reaction is finished, centrifuging, collecting precipitate, extracting by adopting an organic solvent, drying in vacuum to obtain solid powder, dialyzing the solid powder, and freeze-drying to obtain the chitosan oligosaccharide-g-citronellol derivative.
7. The use according to claim 1, wherein the citronellyl bromide is prepared by the following method: slowly dripping a phosphorus tribromide solution into a citronella alcohol solution containing a catalyst according to the volume ratio of 5:2-4, and stirring and reacting for 45-120min under the condition of an ice salt bath; after the reaction is finished, sequentially washing the mixture for 3 to 5 times by using 4 to 6 percent sodium bicarbonate solution, deionized water and saturated saline solution, adding anhydrous magnesium sulfate, drying, filtering, and performing rotary evaporation and concentration to obtain light yellow oily liquid citronellyl bromide; wherein the catalyst is triethylamine, pyridine or ethylenediamine.
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| CN111333750A (en) * | 2020-03-24 | 2020-06-26 | 江南大学 | Chitosan oligosaccharide-N-geraniol derivative and preparation method and application thereof |
| CN111620966A (en) * | 2020-06-23 | 2020-09-04 | 江南大学 | Chitosan oligosaccharide-N-linalool copolymer and preparation method and application thereof |
| CN111732674A (en) * | 2020-07-31 | 2020-10-02 | 江南大学 | Chitosan oligosaccharide-M-cinnamyl alcohol derivative, preparation method and application thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111333750A (en) * | 2020-03-24 | 2020-06-26 | 江南大学 | Chitosan oligosaccharide-N-geraniol derivative and preparation method and application thereof |
| CN111620966A (en) * | 2020-06-23 | 2020-09-04 | 江南大学 | Chitosan oligosaccharide-N-linalool copolymer and preparation method and application thereof |
| CN111732674A (en) * | 2020-07-31 | 2020-10-02 | 江南大学 | Chitosan oligosaccharide-M-cinnamyl alcohol derivative, preparation method and application thereof |
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