CN112028955B - Trimethoxylated arabinose triazole structure spiroisoxazole-pyrrolizine derivative and preparation method and application thereof - Google Patents
Trimethoxylated arabinose triazole structure spiroisoxazole-pyrrolizine derivative and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a spiro isoxazole-pyrrolizine derivative with a trimethoxy substituted arabinose triazole structure and a preparation method and application thereof, firstly, (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one and acetyl arabinose triazole salicylaldoxime are synthesized, then dissolving the compounds in absolute ethyl alcohol, carrying out 1, 3-dipolar cycloaddition reaction, introducing arabinose triazole and isoxazole structures, finally suspending the intermediate compound in methanol, slowly dropwise adding a methanol solution of sodium methoxide under the protection of nitrogen, heating to room temperature for continuous reaction, washing ion exchange resin with methanol, decompressing the filtrate to remove the methanol to obtain a light yellow solid, and carrying out column chromatography separation to obtain the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure. The spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure, which is prepared by the invention, has a strong tumor cell inhibition effect.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a spiro isoxazole-pyrrolizine derivative with a trimethoxy substituted arabinose triazole structure, and a preparation method and application thereof.
Background
Chemical name: (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizin-1-one having the following chemical structural formula:
pyrrolizine is an important component of alkaloids with biological activity, and derivatives thereof are widely applied in the aspects of inflammation diminishing, pain easing, diabetes resisting, sugar anxiety resisting, tumor resisting and the like.
The triazole has aromaticity and abundant electrons in a molecular structure, can interact with enzymes and receptors in organisms by forming hydrogen bonds, and has various biological activities. Glycoside compounds widely exist in organisms and play important physiological functions, and introduction of glycoside into compound molecules can increase water solubility and guidance of the compounds and improve pharmacological properties of the compounds. Recent studies have shown that some compounds containing glycosylated triazole show better inhibition effects on carbonic anhydrase, glycosyltransferase and protein tyrosine phosphatase.
The isoxazoline skeleton is an important pharmacophore in the application of medicines and has obvious physiological and pharmacological activity. In addition, spiroisoxazolines synthesized by 1, 3-dipolar cycloaddition of nitrile oxides to exocyclic double bonds have attracted attention by pharmacologists because of exhibiting some important physiological properties.
The 1, 3-dipolar cycloaddition reaction is the most important method for synthesizing five-membered heterocyclic compounds with good regioselectivity and body selectivity, and is also a more active reaction in heterocyclic pharmaceutical chemistry research. Therefore, the heterocyclic compound has high synthetic value in terms of pharmacology and synthesis angle.
Disclosure of Invention
The invention aims to provide a trimethoxy substituted arabinose triazole structure spiroisoxazole-pyrrolizine derivative, and a preparation method and application thereof.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a spiro isoxazole-pyrrolizine derivative with a trimethoxy-substituted arabinose triazole structure has a chemical structural formula as follows:
wherein-Glu' is an arabinosyl group represented by the formula:
the application also provides a preparation method of the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure, and the preparation method comprises the following steps:
Further, the ratio of the amount of the 2, 3-dihydropyrrolizine-1-one to the amount of the 3,4, 5-trimethoxybenzaldehyde substance is 1:1.
Further, 2-3mL of 40% NaOH aqueous solution was added to 10mmol of 2, 3-dihydropyrrolizin-1-one and 10mmol of 3,4, 5-trimethoxybenzaldehyde, which were dissolved in 20-30mL of ethanol.
Furthermore, the amount ratio of the substances (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one, the acetyl arabinose triazole salicylaldoxime and chloramine T is 1:1: 1.2.
Further, the ratio of the amount of (2S,3R,4S,5S) -2- (4- ((2- (4- (3,4, 5-trimethoxyphenyl) -1 '-oxo-1' H,3'H,4H spiro [ isoxazole-5, 2' -pyrrolizin ] -3-yl) phenoxy) methyl) -1H-1,2, 3-triazol-1-yl) tetrahydro-2H-pyran-3, 4, 5-triacetate to sodium methoxide species is 1: 2.
Further, the volume ratio of chloroform to methanol in the eluent adopted by the column chromatography separation is 20: 1.
The application also provides an application of the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure in the aspect of antitumor drugs.
According to the preparation method, an isoxazole ring is introduced into a chemical structure of (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one by using a 1, 3-dipole cycloaddition method, so that a novel spiro isoxazole-pyrrolizine derivative with a trimethoxy substituted arabinose triazole structure is finally synthesized. The spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure, which is prepared by the invention, has a strong tumor cell inhibition effect, and provides a basis for further application in the medical field.
Drawings
FIG. 1 is a schematic diagram showing the chemical structure of the preparation of (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizin-1-one of the present application;
FIG. 2 is a schematic diagram of a chemical structural formula of a preparation of a spiro isoxazole-pyrrolizine derivative with a trimethoxy substituted arabinose triazole structure.
Detailed Description
The technical solutions of the present invention are further described in detail below with reference to the drawings and examples, which should not be construed as limiting the present invention.
Isoxazole derivatives have attracted much attention as a class of useful intermediates and as a variety of pharmaceutical activities that they themselves exhibit. The general idea of the invention is to skillfully introduce glucoside with biological activity, 1,2, 3-triazole pharmacodynamic structure and five-membered isoxazole ring into the molecular structure of (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one, finally prepare the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure, and improve the pharmacological activity.
The application relates to a spiro isoxazole-pyrrolizine derivative with a trimethoxy substituted arabinose triazole structure, which has the following chemical structural formula:
wherein-Glu' is an arabinosyl group represented by the formula:
the application of the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure is also called as a spiro isoxazole-pyrrolizine derivative with the 3,4, 5-trimethoxy substituted arabinose triazole structure.
The embodiment provides a preparation method of a spiro isoxazole-pyrrolizine derivative with a trimethoxy substituted arabinose triazole structure, which comprises the following steps:
as shown in figures 1 and 2, chemical structural formula 1 in figure 2 is 2, 3-dihydropyrrolizine-1-one, chemical structural formula 2 is 3,4, 5-trimethoxybenzaldehyde, and (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-one, (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-one corresponds to chemical structural formula 3.
The amount ratio of 2, 3-dihydropyrrolizine-1-one to 3,4, 5-trimethoxybenzaldehyde substance is 1:1, each 10mmol of 2, 3-dihydropyrrolizine-1-one and 10mmol of 3,4, 5-trimethoxybenzaldehyde are dissolved in 20-30mL of ethanol, and 2-3mL of 40% NaOH aqueous solution is added.
One example of the present application, synthesis of (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizin-1-one: dissolving 10mmol of 2, 3-dihydropyrrolizine-1-one (compound 1) and 10mmol of 3,4, 5-trimethoxybenzaldehyde (compound 2) in 20mL of ethanol, adding 2mL of 40% NaOH aqueous solution, stirring at 75 ℃ for 4 hours, filtering and separating by using a Buchner funnel, washing a filter cake with water, recrystallizing and purifying by using ethanol, filtering and drying to obtain the product (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-one (compound 3).
In another example, the synthesis of (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizin-1-one: dissolving 10mmol of 2, 3-dihydropyrrolizine-1-one (compound 1) and 10mmol of 3,4, 5-trimethoxybenzaldehyde (compound 2) in 30mL of ethanol, adding 3mL of 40% NaOH aqueous solution, stirring at 85 ℃ for 3 hours, filtering and separating by using a Buchner funnel, washing a filter cake with water, recrystallizing and purifying by using ethanol, filtering and drying to obtain the product (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-one (compound 3).
In another example, the synthesis of (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizin-1-one: dissolving 10mmol of 2, 3-dihydropyrrolizine-1-one (compound 1) and 10mmol of 3,4, 5-trimethoxybenzaldehyde (compound 2) in 20mL of ethanol, adding 2mL of 40% NaOH aqueous solution, stirring at 80 ℃ for 3 hours, filtering and separating by using a Buchner funnel, washing a filter cake with water, recrystallizing and purifying by using ethanol, filtering and drying to obtain the product (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-one (compound 3).
The application dissolves 2, 3-dihydropyrrolizin-1-one and 3,4, 5-trimethoxybenzaldehyde in ethanol, wherein the ethanol is 95% aqueous ethanol. Ethanol is only the reaction solvent and is present in excess. The ethanol is less in 2, 3-dihydropyrrolizine-1-ketone and 3,4, 5-trimethoxybenzaldehyde, and the ethanol is not dissolved and more in the ethanol, so that the molar concentration of the solution is too dilute, and the reaction is slow.
And 2, carrying out dehydration reaction on the acetyl arabinose triazole salicylaldehyde and hydroxylamine hydrochloride to generate the acetyl arabinose triazole salicylaldoxime.
In the embodiment, the preparation of the acetaarabinotriazole salicylaldoxime by the dehydration reaction of the acetaarabinotriazole salicylaldehyde and hydroxylamine hydrochloride comprises the following steps:
suspending acetyl azide arabinose and 2-propargyloxybenzaldehyde in a mixed solvent of dichloromethane and water, heating to 40-44 ℃, and adding sodium ascorbate and CuSO in turn under vigorous stirring4·5H2And O, continuously carrying out reflux reaction for 4-5 hours, stopping the reaction, separating liquid when the solution system of the chemical reaction is cooled to room temperature, and using CH for a water layer2C12Extracting twice, combining organic phases, drying over night by using anhydrous sodium sulfate, carrying out suction filtration, removing the solvent by pressure reduction, and then carrying out flash column chromatography separation to obtain the acetyl arabinose triazole salicylaldehyde;
adding hydroxylamine hydrochloride and water into a reaction bottle, magnetically stirring until the hydroxylamine hydrochloride is dissolved, adding the acetyl arabinose triazole salicylaldehyde and the absolute ethyl alcohol under stirring, violently stirring for 2-3 hours, and adding 20% Na after the reaction is finished2CO3And (3) regulating the pH value of the reaction solution to be neutral, standing and cooling to room temperature to generate a large amount of white precipitate, putting the white precipitate into a refrigerator for a night, filtering under reduced pressure, and drying at room temperature to obtain granular white crystal acetyl arabinose triazole salicylaldoxime.
In this example, the ratio of the amount of the acetyl arabinose triazole salicylaldehyde to the amount of the hydroxylamine hydrochloride species was 4: 5.
For example:
12mmol of acetyl azidoarabinose, 1.60g (10 mmol 1) of 2-propargyloxybenzaldehyde were suspended in 100mL (dichloromethane): (water) ═ 1:1, heating to 40-44 ℃, and adding 0.2mmol of sodium ascorbate and 0.1mmol of CuSO in sequence under vigorous stirring4·5H2And O, continuously carrying out reflux reaction for 4-5 hours, stopping the reaction, separating liquid when the solution system of the chemical reaction is cooled to room temperature (20-30 ℃), and using CH for a water layer2C12Extracting twice (50mL multiplied by 2), combining organic phases, drying over night by anhydrous sodium sulfate, filtering, decompressing, removing a solvent, and separating by fast column chromatography to obtain the acetyl arabinose triazole salicylaldehyde.
Into a 250mL Erlenmeyer flask, 35.6g (0.5mol) of hydroxylamine hydrochloride and 90mL of H were added2And O, magnetically stirring until the hydroxylamine hydrochloride is dissolved (usually stirring by a magnetic stirrer). The arabinofuranotriazole salicylaldehyde (0.4mol) and 50mL of absolute ethanol are weighed into a 250mL conical flask under stirring, and stirred vigorously for 3 hours. After the reaction is finished, 20% Na is used2CO3And (3) adjusting the pH value of the reaction solution to be neutral, standing and cooling to room temperature to generate a large amount of white precipitate, putting the white precipitate into a refrigerator for overnight, filtering under reduced pressure, and drying at room temperature to obtain granular white crystal, namely the acetyl arabinose triazole salicylaldoxime.
It should be noted that, the dehydration reaction of the arabinoside triazole salicylaldehyde and hydroxylamine hydrochloride to generate the arabinoside triazole salicylaldoxime in this embodiment is already a relatively mature technology, and is not described herein again.
And 3, dissolving (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one (compound 3) and acetyl arabinoltriazole salicylaldoxime (compound 4) in absolute ethyl alcohol, adding chloramine T, refluxing for 8-12 hours, carrying out 1, 3-dipolar cycloaddition reaction, introducing an arabinoltriazole and isoxazole structure, recrystallizing with methanol, and drying in vacuum to obtain an intermediate compound 5.
The ratio of the (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one, the acetyl arabinose triazole salicylaldoxime and the chloramine T substance is 1:1: 1.2.
In one example of the present application, 10mmol (e) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizin-1-one (compound 3) and 10mmol of acetoacetarabinotriazole salicylaldoxime (compound 4) are dissolved in 30mL of absolute ethanol, 12mmol of chloramine T is added, reflux is performed for 12 hours, 1, 3-dipolar cycloaddition reaction is performed, arabinotriazole and isoxazole structures are introduced, recrystallization is performed with methanol, and compound 5((2S,3R,4S,5S) -2- (4- ((2- (4- (3,4, 5-trimethoxyphenyl) -1 '-oxo-1' H,3'H,4H spiro [ isoxazole-5, 2' -pyrrolizine ] -3-yl) phenoxy) methyl) -1H-1 is obtained, 2, 3-triazol-1-yl) tetrahydro-2H-pyran-3, 4, 5-triacetate).
As shown in FIG. 2, the chemical structural formula 3 in the figure is (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-one, the chemical structural formula 4 is acetyl arabinose triazole salicylaldoxime, and the chemical structural formula 5 is the generated intermediate compound 5.
The ratio of the amount of compound 5 to the amount of sodium methoxide material in the column chromatography separation is 1:2, and the volume ratio of chloroform to methanol in the eluent used for the column chromatography separation is 20: 1. In this example, 5mmol of compound 5 is suspended in 20mL of methanol, cooled to 0 ℃ with ice water, slowly added dropwise with 0.6mL of a methanol solution of sodium methoxide at a concentration of 1.0mol/L under the protection of nitrogen, reacted at room temperature for 4 hours, monitored by TLC until the starting material point disappears, the system is adjusted to neutral with 732 strong acid styrene cation exchange resin, filtered, the ion exchange resin is washed with methanol, and the filtrate is decompressed to remove methanol to obtain a pale yellow solid, which is separated by column chromatography [ eluent: and obtaining the spiro isoxazole-pyrrolizine derivative 4- (3,4, 5-trimethoxyphenyl) -3- (2- ((1- ((2S,3R,4S,5S) -3,4, 5-trihydroxy tetrahydro-2H-pyran-2-yl) -1H-1,2, 3-triazole-4-yl) methoxyl) phenyl) -1'H,3' H,4H spiro [ isoxazole-5, 2 '-pyrrolizine ] -1' -ketone (compound 6) with the trimethoxy substituted arabinose triazole structure according to the volume ratio (chloroform: methanol ═ 20: 1) ].
As shown in fig. 2, the chemical structural formula 6 is the generated spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure, i.e. compound 6.
The experimental data are as follows: the spiro isoxazole-pyrrolizine derivative (compound 6) with the trimethoxy substituted arabinose triazole structure is light yellow powder, the yield is 26.3 percent, the melting point is m.p.172-174 ℃, and the nuclear magnetic hydrogen spectrum, the infrared spectrogram and the element analysis data are as follows:
1H NMR(DMSO-d6)δ:7.28-7.49(m,4H,Ar-H),6.81(dd,J＝2.1,0.8Hz,1H),6.56(dd,J＝4.1,2.3Hz,1H),6.47(s,1H,C＝C-H),5.82(d,J＝10.0Hz,1H),5.34(d,J＝10.0Hz,1H),8.40(1H,s),7.62(1H,d,J＝6.4H z),7.52～7.53(1H,m),7.35～7.37(1H,m),7.01～7.20(1H,m),5.57(1H,d,J＝9.6H z),5.26(2H,s),5.20(s,1H),4.36(1H,t),4.33(d,J＝12.8Hz,1H),4.01(1H,dd,J＝3.2,10.0Hz),3.90(d,J＝12.8Hz,1H),3.78(1H,t),3.67～3.68(1H,m),3.80(s,3H,-OCH3),3.56(s,6H,-OCH3),3.44～3.46(2H,m)。
IR(KBr)v/cm-1 3450,3433,2916,1694,1603,1458,1242,1095,1047,754
m/e:647(100.0％)。
Anal.calcd.for C32H33N5O10：C,59.35；H,5.17；N,10.83。
in this example, the MTT method is used to determine the in vitro inhibitory effect of compound 6 on different tumor strains, and the results of the determination of the anti-tumor activity of the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure are as follows:
dissolving and diluting compound 6 with DMSO, and obtaining tumor cells HepG2 (liver cancer cell), A375 (melanoma cell), SW620 (human colorectal adenocarcinoma cell), A549 (lung adenocarcinoma cell), SGC7901 (gastric cancer cell), SKOV3 (ovary adenocarcinoma cell)Cancer cells) were seeded into 4000/200. mu.L/well of 96-well plate, and 2. mu.L of compound was added to each well to a final concentration of 12.0. mu.M, 6.0. mu.M, 3.0. mu.M, 1.5. mu.M, together at 37 ℃ with 5% CO2The cells were incubated in an incubator for 72 hours, with DMSO (1%) as a blank control. After 72 hours, MTT was added to a final concentration of 0.25mg/mL and the mixture was left at 37 ℃ with 5% CO2After 4 hours in the cell incubator, the solvent was blotted, 100. mu.l DMSO was added to each well, absorbance (OD value) was measured at 570nm with an enzyme-linked immunosorbent assay, and the data obtained was used to calculate IC50The value is obtained. Selecting compounds with high inhibitory activity, and determining the influence of different action times of the compounds at different concentrations on the human tumor cell cycle and apoptosis.
The test compounds of different concentrations were coarse-screened in 96-well plates and IC was calculated from the resulting inhibition50Values, results are given in the following table.
Table 1 compound 6: IC of trimethoxy substituted arabinose triazole structure spiroisoxazole-pyrrolizine derivative on six tumor cell strains50Value of
TABLE 1
In Table 1, the IC of trimethoxy substituted arabinose triazole structure spiroisoxazole-pyrrolizine derivative (compound 6) on six tumor cell lines is shown50The value shows that the compound 6 has stronger tumor cell inhibition effect on SW620 (human colorectal adenocarcinoma cells), A549 (lung adenocarcinoma cells) and SGC7901 (gastric cancer cells), and provides a foundation for further application in the medical field.
The above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and those skilled in the art can make various corresponding changes and modifications according to the present invention without departing from the spirit and the essence of the present invention, but these corresponding changes and modifications should fall within the protection scope of the appended claims.
Claims (8)
1. The spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure is characterized in that the chemical structural formula of the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure is as follows:
wherein-Glu' is an arabinosyl group represented by the formula:
2. a preparation method of the spiroisoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure according to claim 1, which is characterized by comprising the following steps:
step 1, (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-ketone synthesis: dissolving 2, 3-dihydropyrrolizine-1-ketone and 3,4, 5-trimethoxybenzaldehyde in ethanol, adding 40% NaOH aqueous solution, stirring at 75-85 ℃ for 3-4 hours, filtering and separating by using a Buchner funnel, washing a filter cake, recrystallizing and purifying by using ethanol, filtering and drying to obtain a product (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydropyrrolizine-1-ketone;
step 2, carrying out dehydration reaction on the acetyl arabinose triazole salicylaldehyde and hydroxylamine hydrochloride to generate the acetyl arabinose triazole salicylaldoxime, wherein the chemical structural formula of the acetyl arabinose triazole salicylaldoxime is as follows:
step 3, dissolving (E) -2- (3,4, 5-trimethoxy benzylidene) -2, 3-dihydro pyrrolizine-1-one and acetyl arabinose triazole salicylaldoxime in absolute ethyl alcohol, adding chloramine T, refluxing for 8-12 hours, carrying out 1, 3-dipolar cycloaddition reaction, introducing arabinose triazole and isoxazole structure, recrystallizing with methanol to obtain (2S,3R,4S,5S) -2- (4- ((2- (4- (3,4, 5-trimethoxyphenyl) -1 '-oxy-1' H,3'H,4H spiro [ isoxazole-5, 2' -pyrrolizine ] -3-yl) phenoxy) methyl) -1H-1,2, 3-triazol-1-yl) tetrahydro-2H-pyran-3, 4, 5-triacetate;
step 4, (2S,3R,4S,5S) -2- (4- ((2- (4- (3,4, 5-trimethoxyphenyl) -1 '-oxygen-1' H,3'H,4H spiro [ isoxazole-5, 2' -pyrrolizine ] -3-yl) phenoxy) methyl) -1H-1,2, 3-triazol-1-yl) tetrahydro-2H-pyran-3, 4, 5-triacetate is suspended in methanol, ice water is cooled to-5 ℃ -0 ℃, a methanol solution of sodium methoxide is slowly dripped under the protection of nitrogen, the mixture is heated to room temperature for continuous reaction for 3-4 hours, TLC monitors that the raw material point disappears, 732 strong acid styrene cation exchange resin is used for regulating the system to be neutral, filtering, washing the ion exchange resin with methanol, decompressing the filtrate to remove the methanol to obtain a light yellow solid, and performing column chromatography separation to obtain the spiro isoxazole-pyrrolizine derivative with the trimethoxy-substituted arabinose triazole structure: 4- (3,4, 5-trimethoxyphenyl) -3- (2- ((1- ((2S,3R,4S,5S) -3,4, 5-trihydroxytetrahydro-2H-pyran-2-yl) -1H-1,2, 3-triazol-4-yl) methoxy) phenyl) -1'H,3' H,4H spiro [ isoxazole-5, 2 '-pyrrolizine ] -1' -one.
3. The preparation method of the spiroisoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure as claimed in claim 2, wherein the amount ratio of the 2, 3-dihydro pyrrolizin-1-one to the 3,4, 5-trimethoxybenzaldehyde substance is 1:1.
4. The preparation method of the spiro isoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure as claimed in claim 3, wherein 10mmol 2, 3-dihydro pyrrolizin-1-one and 10mmol 3,4, 5-trimethoxybenzaldehyde are dissolved in 20-30mL ethanol, and 2-3mL 40% NaOH aqueous solution is added.
5. The preparation method of the spiroisoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure according to claim 2, wherein the ratio of the amounts of the (E) -2- (3,4, 5-trimethoxybenzylidene) -2, 3-dihydro pyrrolizin-1-one, the acetyl arabinose triazole salicylaldoxime and the chloramine T is 1:1: 1.2.
6. The method for preparing spiro isoxazole-pyrrolizine derivatives with trimethoxy substituted arabinose triazole structure according to claim 2, wherein the ratio of the amount of (2S,3R,4S,5S) -2- (4- ((2- (4- (3,4, 5-trimethoxyphenyl) -1 '-oxo-1' H,3'H,4H spiro [ isoxazole-5, 2' -pyrrolizin ] -3-yl) phenoxy) methyl) -1H-1,2, 3-triazol-1-yl) tetrahydro-2H-pyran-3, 4, 5-triacetate to sodium methoxide material is 1: 2.
7. The preparation method of the spiroisoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure as claimed in claim 2, wherein the volume ratio of chloroform to methanol in eluent for column chromatography separation is 20: 1.
8. An application of the spiroisoxazole-pyrrolizine derivative with the trimethoxy substituted arabinose triazole structure as claimed in claim 1 in the preparation of drugs for resisting human colorectal adenocarcinoma, lung adenocarcinoma or gastric cancer.
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