CN112110969B - Triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, and preparation method and application thereof - Google Patents

Triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, and preparation method and application thereof Download PDF

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CN112110969B
CN112110969B CN202010471655.2A CN202010471655A CN112110969B CN 112110969 B CN112110969 B CN 112110969B CN 202010471655 A CN202010471655 A CN 202010471655A CN 112110969 B CN112110969 B CN 112110969B
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邓莉平
罗蒙强
沈润溥
徐慧婷
席眉扬
杜奎
程凯
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Hubei Chibi Jiji Industrial Technology Research Institute Co ltd
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Abstract

The invention belongs to the technical field of medicines, and particularly relates to a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, and a preparation method and application thereof. The invention relates to a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, which is specifically named as (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol.

Description

Triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, and preparation method and application thereof
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, and a preparation method and application thereof.
Background
Chemical name: 3-nitro-1-carboxylic acid ethyl ester-7-azaindole, the chemical structural formula is as follows:
Figure BDA0002514474420000011
in the process of drug discovery, 7-azaindole is an important structural unit, and many natural compounds with biological activity all contain 7-azaindole structures, and people find that the structural compounds have wide application and can be used for anticancer, antibacterial, antiviral, antidepressant, hypertension treatment and the like.
The alkaloid can be directly extracted from natural animals and plants, and is used as a lead compound to carry out structural modification and modification on the alkaloid, so that a medicament with more ideal curative effect is found by analyzing the structure-activity relationship with a target spot, and the alkaloid is also a good choice.
Disclosure of Invention
The invention aims to provide a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, and a preparation method and application thereof, and the specific scheme is as follows:
a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, which is specifically named as (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol, the (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol has the following chemical structural formula:
Figure BDA0002514474420000012
a preparation method of triazole glucoside derivatives of 3-nitro-1-ethyl formate-7-azaindole comprises the following steps:
(1) synthesis of N-ethyl formate-7-azaindole: adding 1.18g of 7-azaindole and 10mL of DMF (dimethyl formamide) into a 50mL round-bottom flask, slowly adding 0.6g of NaH under an ice bath condition, stirring for 10 minutes, adding 5mL of DMF (dimethyl formamide) solution dissolved with 1.19g of ethyl chloroformate, stirring at room temperature, monitoring the reaction end point by TLC (thin layer chromatography), after the reaction is finished, adding 20mL of water into the reaction solution, extracting with 20mL of 3 times of ethyl acetate, combining organic layers, and evaporating the solvent to obtain the N-ethyl formate-7-azaindole;
(2) synthesis of 3-nitro-1-ethyl formate-7-azaindole: adding 20mL of acetic anhydride into a 50mL round-bottom flask, slowly dripping 0.2mL of concentrated nitric acid into the round-bottom flask under an ice bath condition, stirring for 10 minutes, directly dripping the reaction solution into 30mL of acetic anhydride solution dissolved with N-ethyl formate-7-azaindole, stirring overnight at room temperature after dripping, monitoring the reaction end point by TLC (thin layer chromatography), pouring the reaction solution onto 50g of ice after the reaction is finished, stirring for 1 hour, extracting with 20mL multiplied by 3 of ethyl acetate, combining organic layers, drying with anhydrous sodium sulfate, evaporating the solvent to dryness, and performing column chromatography by using an eluent to obtain 3-nitro-1-ethyl formate-7-azaindole;
(3) introducing a galactoside triazole structure: mixing 3-nitro-1-ethyl formate-7-azaindole and 1-azido-peracetylgalactose in methanol at room temperature, carrying out [3+2] dipolar cycloaddition reaction, refluxing for about 5 hours, monitoring by TLC until the raw material point disappears, and removing the solvent under reduced pressure until the solvent is dried to obtain the intermediate compound.
(4) And (2) putting the intermediate compound into a reaction bottle, adding methanol and dichloromethane for dissolving, slowly adding sodium methoxide, after dropwise adding for about half an hour, heating, condensing, refluxing and continuing to react for 3-4 hours, monitoring by TLC (thin layer chromatography) until the raw material point disappears, adding cation exchange resin for neutralization under stirring, adjusting the pH value to 5-6, filtering, washing the ion exchange resin for several times by using methanol, decompressing the filtrate to remove the mixed solvent to obtain a yellow solid, performing column chromatography purification by using V (chloroform) and V (methanol) to 15:1, and performing vacuum drying to obtain the triazole glycoside derivative of 3-nitro-1-ethyl formate-7-azaindole.
In the step (3), the ratio of the 3-nitro-1-ethyl formate-7-azaindole to the 1-azide-peracetylgalactose substance is 1: 1.
In the step (4), the volume ratio of the mixed solvent methanol to the dichloromethane is 3:1, and the mass ratio of the intermediate compound to the sodium methoxide is 1: 2.
And (3) eluting agent in the step (2) is V (petroleum ether) and V (ethyl acetate) which are 5: 1.
The triazole glucoside derivative of the 3-nitro-1-ethyl formate-7-azaindole is applied to antitumor drugs.
The application of the triazole glucoside derivative of the 3-nitro-1-ethyl formate-7-azaindole in the aspect of hepatitis B virus resistance.
The 1,2, 3-triazole compound has various biological activities of resisting bacteria, tumors, tuberculosis, viruses, convulsion and the like. Because the structure of the aromatic biodegradable polyester is aromatic, the biodegradable polyester is not easy to be biodegraded; is rich in electrons, can be tightly combined with biomacromolecules through hydrogen bonds and dipole interaction, and is often used as an effective functional group to be introduced into the structure of the existing medicament so as to improve the physicochemical property and pharmacokinetic parameters of the medicament and improve the biological activity of the medicament. The glucoside compound has good antibacterial and anticancer activities. The introduction of a glucoside structure into the compound can enhance the water solubility and targeting property of the compound and improve the pharmacological property of the compound. The present invention introduces this structure.
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. The indole or 7-azaindole becomes an electrophilic reagent with the property similar to that of an electron-deficient olefin after connecting electron-withdrawing groups on the 3-position and the 1-position N, and the research reports on the aspect are relatively less. 7-azaindole, as a member of indole compounds, has important physiological and pharmacological activities, and reports thereof are less than that of indole. Therefore, the research on 7-azaindole and in-situ generated 1, 3-dipole dearomatization cycloaddition reaction is carried out, and the polycyclic 7-azaindoline skeleton derivative is constructed, so that the method has important significance for enriching the application range of azaindole and constructing a compound with physiological activity.
Meanwhile, drug absorption requires appropriate water solubility and lipid solubility to be able to permeate the lipid bilayer of the biological membrane. The transdermal absorption of the medicine in vitro and the dissolution, absorption, distribution and transportation of the medicine in vivo are all related to the lipid-water partition coefficient. 7-azaindole and triazole glucoside structures are combined together to obtain a more ideal lipid-water partition coefficient.
The invention provides a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, namely (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol and a preparation method and application thereof, wherein the preparation method uses a 1, 3-dipolar cycloaddition method to introduce glycosyl triazole ring into the chemical structure of 3-nitro-1-ethyl formate-7-azaindole, thereby finally synthesizing a novel 7-azaindole derivative containing galactose triazole structure. The (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol prepared by the invention has stronger tumor cell inhibition effect and in-vitro anti-hepatitis B virus activity, and provides a foundation for further application in the medical field.
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FIG. 1 is a schematic diagram of a chemical structural formula of a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole.
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.
7-azaindole derivatives are widely concerned as a class of useful intermediates and various pharmaceutical activities shown by the intermediates. The general idea of the invention is to skillfully introduce glucoside with biological activity and 1,2, 3-triazole pharmacodynamic structure into the molecular structure of 3-nitro-1-ethyl formate-7-azaindole, highly specifically prepare (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol and improve pharmacological activity.
The invention relates to a triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole, namely (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol, which has the following chemical structural formula:
Figure BDA0002514474420000051
this embodiment is a method for preparing a triazole glycoside derivative of 3-nitro-1-ethyl formate-7-azaindole, that is, (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridinyl) -tetrahydropyran-3, 4, 5-triol (compound 6), including the steps of:
as shown in fig. 1, chemical formula 1 is 7-azaindole (compound 1), chemical formula 2 is N-ethyl formate-7-azaindole (compound 2), chemical formula 3 is 3-nitro-1-ethyl formate-7-azaindole (compound 3), chemical formula 4 is 1-azido-peracetyl galactose (compound 4), under mild conditions, a dipolar cycloaddition reaction is performed to generate an intermediate 5 (compound 5), the compound 5 is deacetylated to generate a compound corresponding to chemical formula 6, namely (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol (Compound 6).
The specific preparation method of the compound (6) comprises the following steps:
(1) synthesis of N-ethyl formate-7-azaindole: adding 1.18g (10mmol) of 7-azaindole (compound 1) and 10mL of DMF (dimethyl formamide) into a 50mL round-bottom flask, slowly adding 0.6g (25mmol) of NaH under ice bath condition, stirring for 10 minutes, adding 5mL of DMF solution dissolved with 1.19g (11mmol) of ethyl chloroformate, stirring at room temperature, monitoring the reaction end point by TLC (thin layer chromatography), adding 20mL of water into the reaction solution after the reaction is finished, extracting with 20mL of ethyl acetate multiplied by 3, combining organic layers, and evaporating the solvent to obtain N-ethyl formate-7-azaindole (compound 2);
(2) synthesis of 3-nitro-1-ethyl formate-7-azaindole: adding 20mL of acetic anhydride into a 50mL round-bottom flask, slowly dripping 0.2mL of concentrated nitric acid into the round-bottom flask under an ice bath condition, stirring for 10 minutes, directly dripping the reaction solution into 30mL of acetic anhydride solution dissolved with N-ethyl formate-7-azaindole, stirring overnight at room temperature after dripping, monitoring the reaction end point by TLC, pouring the reaction solution onto 50g of ice after the reaction is finished, stirring for 1 hour, extracting with 20mL of ethyl acetate multiplied by 3, combining organic layers, drying with anhydrous sodium sulfate, evaporating the solvent to dryness, and performing column chromatography by using V (petroleum ether) column and V (ethyl acetate) column of 5:1 as eluent to obtain 3-nitro-1-ethyl formate-7-azaindole (compound 3);
(3) introducing a galactoside triazole structure: 31.7mg (0.1mmol) of 3-nitro-1-carboxylic acid ethyl ester-7-azaindole and 37.3mg (0.1mmol) of 1-azido-peracetylgalactose (compound 4) were mixed in methanol at room temperature to carry out [3+2] dipolar cycloaddition reaction, and after refluxing for about 5 hours, TLC was monitored until the starting material point disappeared, and the solvent was removed under reduced pressure to dryness to give intermediate compound 5.
(4) Taking an intermediate compound 5(0.2mmo1) into a reaction bottle, adding 12mL of methanol and 3mL of dichloromethane for dissolving, slowly adding sodium methoxide (0.98mL, 0.41mol/L and 0.4mmo1), after dropwise adding for about half an hour, heating, condensing, refluxing and continuously reacting for 3-4 hours, monitoring by TLC until a raw material point disappears, adding cation exchange resin for neutralization under stirring, adjusting the pH to 5-6, filtering, washing the ion exchange resin for a plurality of times by using methanol, removing a mixed solvent from a filtrate under reduced pressure to obtain a yellow solid, purifying by using column chromatography with V (chloroform) to V (methanol) 15:1, and drying in vacuum to obtain a compound 6.
As shown in fig. 1, the chemical structural formula 6 is triazole glycoside derivative of 3-nitro-1-ethyl formate-7-azaindole, namely (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol.
The experimental data are as follows: (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-carboxylic acid ethyl ester-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridinyl) -tetrahydropyran-3, 4, 5-triol (compound 6) as a pale yellow powder in 56.3% yield, m.p.156-157 ℃ melting point, and its nuclear magnetic hydrogen spectrum, infrared spectrum and elemental analysis data are as follows:
1HNMR(DMSO-d6)δ:8.49～8.47(m,1H),7.82～7.80(m,1H),7.03(dd，J＝7.2，4.8Hz，1H)，5.50(dd，J＝6.8，3.6Hz，1H)，4.86-3.40(m,11H,7×GalactosylH,OH)，3.61(d，J＝9.6Hz，2H)，1.37(t，J＝7.2Hz，3H)；
IR(KBr)v/cm-13446,3430,2983,1707,1632,1576,1462,1209,1162,1092,753
m/e:440(100.0％)。
Anal.calcd.forC16H20N6O9：C,43.64；H,4.58；N,19.08；foundC,43.63；H,4.60；N,19.06；。
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 antitumor activity of (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-ethyl formate-4, 8 b-dihydro- [1,2,3] triazole pyrrolopyridinyl) -tetrahydropyran-3, 4, 5-triol (compound 6) are as follows:
compound 6 was diluted with DMSO, and tumor cells HepG2 (liver cancer cells), A375 (melanoma cells), SW620 (human colorectal adenocarcinoma cells), A549 (lung adenocarcinoma cells), SGC7901 (stomach cancer cells), SKOV3 (ovarian cancer cells) were plated in a 96-well plate at 4000/200. mu.L/well, and 2. mu.L of compound was added to each well at a final concentration of 12.0. mu.M, 6.0. mu.LM, 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 of DMSO was added to each well, absorbance (OD value) was measured at 570nm with an enzyme-linked immunosorbent assay, and the obtained data 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 table below.
TABLE 1 Compound 6(2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-carboxylic acid ethyl ester-4, 8 b-dihydro- [1,2,3]Triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol) on six tumor cell lines50Value of
Figure BDA0002514474420000071
In Table 1, (2S,3S,4R,5S) -2- (hydroxymethyl) -6- (8 b-nitro-4-carboxylic acid ethyl ester-4, 8 b-dihydro- [1,2,3]IC of triazole pyrrolopyridyl) -tetrahydropyran-3, 4, 5-triol (compound 6) on six tumor cell lines50The value shows that the compound 6 has stronger tumor cell inhibition effect on HepG2 (liver cancer cells) and SGC7901 (stomach cancer cells), and provides a foundation for further application in the medical field.
The target compounds were tested for anti-HBV activity. Taking HepG22.2.15 cells in logarithmic phase, washing with 0.02% EDTA for 2 times, digesting with 0.25% trypsin, blowing uniformly, and counting to 2.5 × 10 cells/mL-1And (4) inoculating the cells into a 24-well plate, wherein each well is 0.5mL, and the administration is started after the cells are attached to the wall. Samples were prepared at 12.5, 25, 50. mu.g/mL in DMSO-containing medium -13 concentrations of DMS0 were added to 24-well culture plates, 0.6mL per well, and 2 wells per concentration, and cells containing the same amount of DMS0 were used as control groups instead of the drug solution. The 3 rd day is changed into the same concentration liquid medicine, and the second day is administeredCells were collected on day 6. After washing 2 times with Phosphate Buffered Saline (PBS), extraction was performed with a reagent for extracting virus core particles. And (3) adopting a Taqman probe to perform fluorescent quantitative PCR to determine the content of HBVDNA in the cells. The inhibition rate of the sample on the replication of hbv dna in the cells was calculated by the formula (control group copy number-administration group copy number)/control group copy number × 100%. The compound 6 has inhibition effect on the replication of HBVDNA in HepG22.2.15 cells, and presents a certain dose-effect relationship. As can be seen from Table 2, compound 6 was present at 50. mu.g/mL-1The inhibition rate on HBVDNA is 90.32%, and the in vitro anti-HBV activity is better.
TABLE 2 replication inhibition of HBV DNA cells by Compound 6
Figure BDA0002514474420000081
Drug absorption requires appropriate water and lipid solubility to be able to permeate the biofilm lipid bilayer. The n-octanol/water partition coefficient is of great significance for predicting drug absorption in vivo. The lipid-water partition coefficient is an important parameter for expressing lipophilicity and ability to permeate biological membranes of a compound. The transdermal absorption of the medicine in vitro and the dissolution, absorption, distribution and transportation of the medicine in vivo are all related to the lipid-water distribution coefficient. It is generally considered that the lipid-water partition coefficient P is too low (1ogP < -2), and the compound cannot pass through the lipid membrane; conversely, if the P value is too high (1ogP >3), the compound is difficult to release from the membrane on the other side of the cell because of its high lipid solubility, and enters the nearby blood or lymph vessels. The experimental result shows that the LogP of the n-octanol/water distribution coefficient of the compound 6 is 2.87, is relatively ideal and meets the principle of patent medicine.
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 (7)

1. The triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole is characterized by having a chemical structural formula as follows:
Figure 15316DEST_PATH_IMAGE001
2. a method for preparing triazole glycoside derivatives of 3-nitro-1-ethyl formate-7-azaindole according to claim 1, comprising the steps of:
(1) synthesis of N-ethyl formate-7-azaindole: adding 1.18g of 7-azaindole and 10mL of DMF (dimethyl formamide) into a 50mL round-bottom flask, slowly adding 0.6g of NaH under an ice bath condition, stirring for 10 minutes, adding 5mL of DMF (dimethyl formamide) solution dissolved with 1.19g of ethyl chloroformate, stirring at room temperature, monitoring the reaction end point by TLC (thin layer chromatography), after the reaction is finished, adding 20mL of water into the reaction solution, extracting with 20mL of 3 times of ethyl acetate, combining organic layers, and evaporating the solvent to obtain N-ethyl formate-7-azaindole;
(2) synthesis of 3-nitro-1-ethyl formate-7-azaindole: adding 20mL of acetic anhydride into a 50mL round-bottom flask, slowly dropping 0.2mL of concentrated nitric acid into the flask under an ice bath condition, stirring for 10 minutes, directly dropping the reaction solution into 30mL of acetic anhydride solution dissolved with N-ethyl formate-7-azaindole, stirring overnight at room temperature after the dropping is finished, monitoring the reaction end point by TLC (thin layer chromatography), pouring the reaction solution onto 50g of ice after the reaction is finished, stirring for 1 hour, extracting with 20mL of ethyl acetate multiplied by 3, combining organic layers, drying with anhydrous sodium sulfate, evaporating the solvent to dryness, and carrying out column chromatography by using an eluent to obtain 3-nitro-1-ethyl formate-7-azaindole;
(3) introducing a galactoside triazole structure: mixing 3-nitro-1-ethyl formate-7-azaindole and 1-azido-peracetylgalactose in methanol at room temperature to perform [3+2] dipolar cycloaddition reaction, refluxing for about 5 hours, monitoring by TLC until the raw material point disappears, and removing the solvent under reduced pressure until the solvent is dried to obtain an intermediate compound;
(4) putting the intermediate compound into a reaction bottle, adding methanol and dichloromethane for dissolving, slowly adding sodium methoxide, after dropwise adding for about half an hour, heating, condensing, refluxing and continuing to react for 3-4 hours, monitoring by TLC (thin layer chromatography) until the raw material point disappears, adding cation exchange resin for neutralization under stirring, adjusting the pH to 5-6, filtering, washing the ion exchange resin for several times by using methanol, decompressing the filtrate to remove the mixed solvent to obtain a yellow solid, performing column chromatography purification by using chloroform and methanol at a volume ratio of 15:1, and performing vacuum drying to obtain the triazole glycoside derivative of 3-nitro-1-ethyl formate-7-azaindole.
3. The preparation method of the triazole glycoside derivative of 3-nitro-1-ethyl formate-7-azaindole as claimed in claim 2, characterized in that: in the step (3), the ratio of the 3-nitro-1-ethyl formate-7-azaindole to the 1-azide-peracetylgalactose substance is 1: 1.
4. The preparation method of the triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole as claimed in claim 2, which is characterized in that: in the step (4), the volume ratio of the mixed solvent methanol to the dichloromethane is 3:1, and the mass ratio of the intermediate compound to the sodium methoxide is 1: 2.
5. The preparation method of the triazole glycoside derivative of 3-nitro-1-ethyl formate-7-azaindole as claimed in claim 2, characterized in that: and (3) eluting the eluent in the step (2) by using petroleum ether and ethyl acetate, wherein the volume ratio of the petroleum ether to the ethyl acetate is 5: 1.
6. Application of the triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole as defined in claim 1 in preparation of drugs for inhibiting HepG2 cells or SGC7901 cells.
7. An application of the triazole glucoside derivative of 3-nitro-1-ethyl formate-7-azaindole as claimed in claim 1 in preparing anti-hepatitis B virus medicines.
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