High isotope abundance deuterium-labeled gibberellin GA3 compound and preparation method and application thereof

Abstract

The invention discloses a deuterium labeled gibberellin GA3 compound with high isotope abundance. The molecular formula of the deuterium labeled gibberellin GA3 compound is C19H20D2O6. The invention also discloses a preparation method and application of the compound. According to the deuterium-labeled gibberellin GA3 compound with high isotope abundance, the isotope abundance of deuterium exceeds 99%, a relatively cheap standard sample with higher sensitivity is provided, and an important support is provided for researches on metabolic pathways, pharmacodynamics, pharmacokinetics and the like of the gibberellin GA3 compound.

Description

Technical Field

[0001] The present invention relates to the field of compound synthesis, and in particular to a high-isotope-abundance deuterium-labeled gibberellin GA3 compound, a preparation method thereof, and an application thereof. Background Art

[0002] Gibberellin Acid (GA3) is a chemical compound named (1S,2S,4aR,4bR,7S,9aS,10S,10aR)-2,7-dihydroxy-1-methyl-8-methylene-13-oxo-1,2,4b,5,6,7,8,9,10,10a-decahydro-4a,1-(epoxymethylene)-7,9a-methylbenzene[a]azepine-10-carboxylic acid. The molecular formula of Gibberellin Acid (GA3) is C 19 H 22 O6, molecular weight is 346.38, and the structural formula is as follows:

[0003]

[0004] Since the initial isolation of crude gibberellic acid (GA3) in 1938, research on GA3 has spanned over 80 years. GA3 is currently the most widely used plant growth regulator in agriculture, forestry, and horticulture in my country. Its primary physiological effects include altering the ratio of male to female flowers in certain crops, inducing parthenocarpy, accelerating fruit growth, and promoting fruit set; breaking seed dormancy, accelerating seed germination, and accelerating stem elongation and bolting in some crops; expanding leaf area, accelerating shoot growth, promoting the accumulation of metabolites in the phloem, and activating the cambium; and inhibiting maturation and senescence, controlling lateral bud dormancy, and promoting tuber formation.

[0005] The applications of stable isotope labeled compounds are mainly reflected in the following aspects:

[0006] 1. In vivo metabolic experiments: Stable isotope labels play an important role in in vivo metabolic experiments in animals or plants. They are used to confirm metabolic pathways, explore disease mechanisms, discover new regulatory principles, confirm new therapeutic targets and biomarkers, etc. Commonly used tracers include deuterium (2H), carbon-13 ( 13 C), carbon-15 ( 15 N), oxygen-18 ( 18 These markers can be administered into the body to analyze downstream metabolites and identify upstream and downstream metabolic pathways and their relationships.

[0007] 2. Proteomics research: In proteomics research, stable isotope labeling techniques such as SILAC (stable isotope labeling with amino acids in cell culture) and SILAM (stable isotope labeling in mammals) are widely used. These techniques introduce heavy stable isotope-labeled amino acids into cells or animals, allowing researchers to quantitatively analyze changes in the proteome, thereby gaining a deeper understanding of the role of proteins in health and disease.

[0008] 3. Drug R&D: Stable isotope labeling technology also has important applications in drug R&D. By using stable isotope-labeled compounds, we can study the metabolic pathways, pharmacodynamics, and pharmacokinetics of drugs in animals or plants, thereby optimizing drug design and improving drug efficacy.

[0009] Since stable isotope labeling does not change the function of drug molecules, it becomes the best means to detect and quantify drugs and their metabolites. For example, the introduction of deuterium (2H) is particularly economical and 13 C and 15 N labeling is simpler and more readily available. Polydeuterium-labeled drug molecules can effectively eliminate matrix effects, making them ideal internal standards for mass spectrometry measurements. Furthermore, the high specific activity of tritium-labeled compounds plays a key role in nanomolar ligand binding affinity studies and in vivo compound distribution imaging using autoradiography. These applications not only advance basic scientific research but also provide important tools and methods for drug development and disease treatment. Stable isotope labeling technology is of great significance in drug development.

[0010] Isotope dilution mass spectrometry (IDMS) uses a reference material with a natural isotopic composition as a reference diluent to calibrate the concentration of the enriched isotope. This enriched isotope is then used as the diluent to measure unknown samples. The position, number, and abundance of the labeled atoms in an isotope-labeled compound significantly influence the expected sensitivity and, consequently, the accuracy and reliability of the test values. Insufficient isotopic abundance can result in poor sensitivity, and the accuracy and reliability of the test values can also be compromised.

[0011] Zeitschrift fur Chemie, 1984 (24), 4, 152-153, Chem. Commun., 2014, 50, 5224-5226. and other literatures mentioned the synthesis of stable isotope labeled gibberellin GA3 compounds. Among them, Zeitschrift fur Chemie, 1984 (24), 4, 152-153. disclosed a The synthesis reaction only introduces one deuterium atom, and the resulting gibberellin GA3-d1 compound has an isotopic abundance of only 90%. Chem. Commun., 2014, 50, 5224-5226. The reaction introduced three 13 C atom, the resulting product is gibberellin GA3- 13 C3 compound, but its synthetic raw materials are expensive, the route is long and the cost is high.

[0012] Therefore, it is necessary to develop new high-isotope abundance deuterium-labeled gibberellin GA3 compounds and their preparation methods to increase isotope abundance and reduce preparation costs. Summary of the Invention

[0013] Purpose of the invention: In response to the shortcomings and defects of the existing technology, the present invention provides a high-isotope abundance deuterium-labeled gibberellin GA3 compound and its preparation method and application. The deuterium isotope abundance exceeds 99%, providing a more sensitive and relatively inexpensive standard sample, which provides important support for the research on the metabolic pathways, pharmacodynamics and pharmacokinetics of gibberellin GA3 compounds.

[0014] Technical solution: A high isotope abundance deuterium-labeled gibberellin GA3 compound of the present invention is characterized in that: the molecular formula of the compound is C 19 H 20 D2O6, the structural formula is:

[0015]

[0016] The method for preparing a high-isotope-abundance deuterium-labeled gibberellin GA3 compound of the present invention is characterized by comprising the following steps:

[0017] 1) Dissolve compound I in an organic solvent:

[0018]

[0019] 2) Add a base and a silicon etherification reagent to an organic solvent, stir and react for 1 h to 45 h, and recrystallize to obtain compound II:

[0020]

[0021] 3) Compound II was dissolved in an organic solvent, an organic base was added, ozone was introduced at -40°C to 20°C, and the mixture was stirred for 1h to 15h. Compound III was obtained by recrystallization:

[0022]

[0023] 4) Compound III is dissolved in a deuterated solvent, an organic base is added, and the reaction is carried out for 1 to 30 hours. Compound IV is obtained by recrystallization:

[0024]

[0025] 5) Compound V was dissolved in an organic solvent, and a base was added under ice-cooling and stirred for 10 min. Compound IV was added and reacted for 1 h to 18 h. Compound VI was obtained by recrystallization:

[0026]

[0027] 6) Compound VI was dissolved in an organic solvent, acid was added, and the mixture was stirred for 1 to 28 hours. Compound VII was obtained by recrystallization, i.e., a high isotope abundance deuterium-labeled gibberellin GA3 compound:

[0028]

[0029] Wherein, the organic solvent in step 1) and step 2) is N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone; the base is triethylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine, cesium carbonate, potassium carbonate or sodium carbonate; the silicon etherification agent is trimethylchlorosilane, tert-butyldimethylchlorosilane, triisopropylchlorosilane or tert-butyldiphenylchlorosilane; and the reaction temperature during stirring is 5°C to 40°C.

[0030] Preferably, the organic solvent is N,N-dimethylformamide or N,N-dimethylacetamide; the base is potassium carbonate or cesium carbonate; and the silicon etherification agent is tert-butyldiphenylchlorosilane.

[0031] Furthermore, the organic solvent is N,N-dimethylacetamide; the base is cesium carbonate; the silicon etherification agent is tert-butyldiphenylchlorosilane; the reaction temperature during stirring is 7° C. to 40° C., and the reaction time is 2 h to 35 h.

[0032] Wherein, the organic solvent in step 3) is diethyl ether, tetrahydrofuran, 1,4-dioxane, dichloromethane or chloroform; the organic base is triethylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine or pyridine; the molar ratio of compound II to the organic base is 1:0.1 to 1:5.3; and the reaction temperature during stirring is -40°C to 20°C.

[0033] Preferably, the organic solvent is diethyl ether, tetrahydrofuran, dichloromethane or chloroform; the organic base is 4-dimethylaminopyridine or pyridine; the molar ratio of compound II to the organic base is 1:0.1 to 1:5.0; the reaction temperature during stirring is -40°C to 15°C, and the reaction time is 1h to 13h.

[0034] Furthermore, the organic solvent is tetrahydrofuran; the organic base is 4-dimethylaminopyridine; the molar ratio of compound II to the organic base is 1:1.5 to 1:3.0; the reaction temperature during stirring is -30°C to -5°C, and the reaction time is 2h to 11h.

[0035] Wherein, the deuterated solvent in step 4) is a mixed solvent formed by one of methanol-OD, ethanol-OD, isopropanol-OD and deuterated water; the organic base is triethylamine, N,N-diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene or 4-dimethylaminopyridine; and the reaction temperature is 10°C to 80°C.

[0036] Preferably, the deuterated solvent is a mixed solvent formed by isopropyl alcohol-OD and deuterated water; the organic base is triethylamine, N,N-diisopropylethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene; the reaction temperature is 20°C to 80°C, and the reaction time is 3h to 30h.

[0037] Furthermore, the deuterated solvent is a mixed solvent formed by isopropyl alcohol-OD and deuterated water; the organic base is triethylamine; the reaction temperature is 20° C. to 75° C., and the reaction time is 5 h to 26 h.

[0038] Wherein, the organic solvent in step 5) is diethyl ether, tetrahydrofuran or ethylene glycol dimethyl ether; the base is lithium bistrimethylsilylamide, n-butyl lithium, sodium hydride, potassium tert-butoxide, sodium tert-butoxide or lithium diisopropylamide; and the reaction temperature is 0-50°C.

[0039] Preferably, the organic solvent is diethyl ether or ethylene glycol dimethyl ether; the base is lithium bis(trimethylsilyl)amide, n-butyl lithium, sodium hydride or lithium diisopropylamide; the reaction temperature is 0-45° C., and the reaction time is 1 h to 16 h.

[0040] Furthermore, the organic solvent is ethylene glycol dimethyl ether; the base is lithium bis(trimethylsilyl)amide; the reaction temperature is 0-40° C., and the reaction time is 1 h to 12 h.

[0041] Wherein, the organic solvent in step 6) is a mixed solvent formed by one of diethyl ether, methyl tert-butyl ether, tetrahydrofuran or 1,4-dioxane and water; the acid is formic acid, acetic acid, propionic acid, pivalic acid, hydrochloric acid or sulfuric acid; and the reaction temperature is -10°C to 60°C.

[0042] Preferably, the organic solvent is a mixed solvent of tetrahydrofuran or 1,4-dioxane and water; the acid is acetic acid or pivalic acid; the reaction temperature is -10°C to 45°C, and the reaction time is 1h to 25h.

[0043] Furthermore, the organic solvent is a mixed solvent formed by one of 1,4-dioxane and water; the acid is pivalic acid; the reaction temperature is 0-40° C., and the reaction time is 1 h to 20 h.

[0044] The high-isotope-abundance deuterium-labeled gibberellin GA3 compound of the present invention is used as a standard sample in the quality control of gibberellin GA3 medicine and in pharmacological research.

[0045] Among them, the isotope dilution mass spectrometry method uses high isotope abundance deuterium-labeled gibberellin GA3 compounds as standard samples, providing important support for the study of the metabolic pathways, pharmacodynamics and pharmacokinetics of gibberellin GA3 compounds.

[0046] Principle of the invention: The deuterium isotope abundance of the deuterium in the deuterium-labeled gibberellin GA3 of the present invention exceeds 99%. The high isotope abundance deuterium labeling can provide extremely high sensitivity and provide a standard sample for drug quality control in the production process of gibberellin GA3. Compared with Zeitschrift fur Chemie, 1984 (24), 4, 152-153, the deuterium exchange is carried out under the conditions of potassium tert-butoxide / deuterium water under ultraviolet light irradiation, but only one deuterium atom can be introduced, and its isotope abundance is only 90%, and the mixture obtained is difficult to separate. The technology of the present invention uses relatively mild reaction conditions, avoids the reaction conditions that may cause the substrate to lose deuterium, and improves the stability of deuterium. It provides important support for the study of the metabolic pathway, pharmacodynamics and pharmacokinetics of gibberellin GA3 compounds through isotope dilution mass spectrometry (IDMS). More accurate and reliable test results can be obtained, which plays an important role in the scientific evaluation of the quality, safety and efficacy of drugs.

[0047] Beneficial Effects: Compared with existing technologies, the present invention has the following significant advantages: the deuterium-labeled gibberellin GA3 compound obtained in the present invention contains one more deuterium than the deuterium-labeled gibberellin GA3 compound obtained in the prior art; the deuterium isotopic abundance in the compound exceeds 99%, and the high isotopic abundance significantly enhances sensitivity; the preparation method of the present invention is simple to operate, has a reasonable process design, relatively mild reaction conditions, and a high yield. The chemical purity of the product gibberellin GA3 compound is high, with an HPLC purity analysis of 99.41%. Industrial production is achievable, and the high-isotopic-abundance deuterium-labeled gibberellin GA3 compound provides a more sensitive and relatively inexpensive standard sample, providing important support for research on the metabolic pathways, pharmacodynamics, and pharmacokinetics of gibberellin GA3 compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 This is a synthesis diagram of the high isotope abundance deuterium-labeled gibberellin GA3 compound of the present invention;

[0049] Figure 2 The NMR spectrum of the high isotope abundance deuterium-labeled gibberellin GA3 compound of the present invention;

[0050] Figure 3 The HPLC spectrum of the high isotope abundance deuterium-labeled gibberellin GA3 compound of the present invention. DETAILED DESCRIPTION

[0051] The technical solution of the present invention is further described below in conjunction with the accompanying drawings and specific implementation methods.

[0052] Example 1:

[0053] Preparation method of the high isotope abundance deuterium-labeled gibberellin GA3 compound of this embodiment:

[0054] Compound I (3.00 g, 0.009 mol) was dissolved in 15 mL of N,N-dimethylacetamide, and cesium carbonate (11.29 g, 0.035 mol) and tert-butyldiphenylsilyl chloride (7.86 g, 0.029 mol) were added. The mixture was stirred at 10°C for 37 hours. The reaction solution was poured into 6 mL of aqueous solution and extracted with ethyl acetate. After the organic phase was dried, n-hexane was added for recrystallization to obtain 4.32 g of off-white solid Compound II with a yield of 46.90%.

[0055] Compound II (3.10 g, 0.003 mol) was dissolved in 25 mL of tetrahydrofuran, 4-dimethylaminopyridine (0.14 g, 0.001 mol) was added, and ozone was introduced at -30°C with stirring for 9 hours. The reaction solution was poured into 25 mL of 10% aqueous sodium sulfite solution and extracted with ethyl acetate. After the organic phase was dried, ether was added and recrystallized to obtain 1.09 g of white solid Compound III with a yield of 35.10%.

[0056] Compound III (1.97 g, 0.002 mol) was dissolved in 7.9 mL of isopropanol-OD and 2.0 mL of deuterated water, and triethylamine (0.043 g, 0.0004 mol) was added. The mixture was stirred at 35 ° C for 23 hours. The reaction solution was poured into 15 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, ether was added and recrystallized to obtain 1.05 g of off-white solid compound IV with a yield of 53.20%.

[0057] Compound V (1.18 g, 0.003 mol) was dissolved in 16 mL of ethylene glycol dimethyl ether. Lithium bistrimethylsilylamide (1 mol / L in THF) (2.9 mL, 0.003 mol) was added under ice cooling and stirred for 10 minutes. Compound IV (1.56 g, 0.002 mol) was added and stirred at 8°C for 6 hours. The reaction solution was poured into 15 mL of saturated brine and extracted with ethyl acetate. After drying the organic phase, n-hexane was added for recrystallization to obtain 0.69 g of white solid compound VI with a yield of 44.31%.

[0058] Compound VI (0.95 g, 0.001 mol) was dissolved in 5.7 mL of 1,4-dioxane and 1.9 mL of water, and pivalic acid (0.11 g, 0.001 mol) was added. The mixture was stirred at 5°C for 16 hours. The reaction solution was poured into 14 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, acetonitrile was added for recrystallization to obtain 0.16 g of white solid compound VII with a yield of 51.42%.

[0059] Example 2:

[0060] Preparation method of the high isotope abundance deuterium-labeled gibberellin GA3 compound of this embodiment:

[0061] Compound I (5.00 g, 0.014 mol) was dissolved in 25 mL of N,N-dimethylacetamide, and cesium carbonate (18.81 g, 0.058 mol) and tert-butyldiphenylsilyl chloride (13.09 g, 0.048 mol) were added. The mixture was stirred at 27 ° C for 13 hours. The reaction solution was poured into 10 mL of aqueous solution and extracted with ethyl acetate. After the organic phase was dried, n-hexane was added for recrystallization to obtain 13.86 g of off-white solid Compound II with a yield of 90.28%.

[0062] Compound II (2.83 g, 0.003 mol) was dissolved in 23 mL of tetrahydrofuran, and 4-dimethylaminopyridine (0.83 g, 0.007 mol) was added. Ozone was introduced at -23°C and stirred for 7 hours. The reaction solution was poured into 23 mL of 10% aqueous sodium sulfite solution and extracted with ethyl acetate. After the organic phase was dried, diethyl ether was added and recrystallized to obtain 2.45 g of white solid Compound III with a yield of 86.41%.

[0063] Compound III (1.44 g, 0.001 mol) was dissolved in 5.8 mL of isopropanol-OD and 1.4 mL of deuterated water, and triethylamine (0.032 g, 0.0003 mol) was added. The mixture was stirred at 46 ° C for 13 hours. The reaction solution was poured into 10 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, ether was added for recrystallization to obtain 1.32 g of off-white solid compound IV with a yield of 91.49%.

[0064] Compound V (1.03 g, 0.003 mol) was dissolved in 14 mL of ethylene glycol dimethyl ether. Lithium bistrimethylsilylamide (1 mol / L in THF) (2.6 mL, 0.003 mol) was added under ice cooling and stirred for 10 minutes. Compound IV (1.36 g, 0.001 mol) was added and stirred at 21°C for 4 hours. The reaction solution was poured into 14 mL of saturated brine and extracted with ethyl acetate. After drying the organic phase, n-hexane was added for recrystallization to obtain 1.18 g of white solid Compound VI with a yield of 86.93%.

[0065] Compound VI (1.02 g, 0.001 mol) was dissolved in 6.1 mL of 1,4-dioxane and 2 mL of water, and pivalic acid (0.12 g, 0.001 mol) was added. The mixture was stirred at 16°C for 12 hours. The reaction solution was poured into 16 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, acetonitrile was added for recrystallization to obtain 0.29 g of white solid compound VII with a yield of 86.80%.

[0066] Example 3:

[0067] Preparation method of the high isotope abundance deuterium-labeled gibberellin GA3 compound of this embodiment:

[0068] Compound I (2.50 g, 0.007 mol) was dissolved in 12.5 mL of N,N-dimethylacetamide, and cesium carbonate (9.41 g, 0.029 mol) and tert-butyldiphenylsilyl chloride (6.55 g, 0.024 mol) were added. The mixture was stirred at 38 ° C for 21 hours. The reaction solution was poured into 5 mL of aqueous solution and extracted with ethyl acetate. After the organic phase was dried, n-hexane was added for recrystallization to obtain 2.93 g of off-white solid Compound II with a yield of 38.17%.

[0069] Compound II (1.96 g, 0.002 mol) was dissolved in 16 mL of tetrahydrofuran, and 4-dimethylaminopyridine (1.06 g, 0.009 mol) was added. Ozone was introduced at -5°C and stirred for 3 hours. The reaction solution was poured into 16 mL of 10% aqueous sodium sulfite solution and extracted with ethyl acetate. After the organic phase was dried, ether was added and recrystallized to obtain 1.17 g of white solid Compound III with a yield of 59.58%.

[0070] Compound III (1.55 g, 0.001 mol) was dissolved in 6.2 mL of isopropanol-OD and 1.6 mL of deuterated water, and triethylamine (0.034 g, 0.0003 mol) was added. The mixture was stirred at 59 ° C for 9 hours. The reaction solution was poured into 12 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, ether was added for recrystallization to obtain 1.09 g of off-white solid compound IV with a yield of 70.19%.

[0071] Compound V (0.99 g, 0.003 mol) was dissolved in 13 mL of ethylene glycol dimethyl ether. Lithium bistrimethylsilylamide (1 mol / L in THF) (2.5 mL, 0.002 mol) was added under ice cooling and stirred for 10 minutes. Compound IV (1.31 g, 0.001 mol) was added and stirred at 33 ° C for 3 hours. The reaction solution was poured into 13 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, n-hexane was added for recrystallization to obtain 0.45 g of white solid compound VI with a yield of 34.41%.

[0072] Compound VI (1.18 g, 0.001 mol) was dissolved in 7.1 mL of 1,4-dioxane and 2.4 mL of water, and pivalic acid (0.14 g, 0.001 mol) was added. The mixture was stirred at 28°C for 10 hours. The reaction solution was poured into 19 mL of saturated brine and extracted with ethyl acetate. After the organic phase was dried, acetonitrile was added for recrystallization to obtain 0.25 g of white solid compound VII with a yield of 64.68%. (99.41% HPLC), the isotopic abundance of deuterium is 99.11%, and the yield is 57.98%; 1H NMR (400 MHz, DMSO~d6): δ12.60 (br, 1H), 6.33 (d, 1H), 5.79 (dd, 1H), 5.58 (d, 1H), 5.12 (s, 1H), 4.85 (s, 2H), 3.87 (t, 1H), 3.07 (d, 1H), 2.48 (d, 1H), 1.87 (m, 2H), 1.66 (m, 5H), 1.07 (s, 3H).

[0073] Effect Analysis: The deuterium-labeled gibberellin GA3 compound of the present invention contains one more deuterium than the deuterium-labeled compound obtained by the prior art; the deuterium isotopic abundance in the compound exceeds 99%, significantly enhancing its sensitivity. The preparation method of the present invention is simple to operate, has a rational process design, and employs relatively mild reaction conditions, resulting in a high yield. The chemical purity of the product gibberellin GA3 compound is high, reaching 99.41% by HPLC analysis. Industrial production is feasible, and the high-isotopic-abundance deuterium-labeled gibberellin GA3 compound provides a more sensitive and relatively inexpensive standard sample, providing important support for research on the metabolic pathways, pharmacodynamics, and pharmacokinetics of gibberellin GA3 compounds.

Claims

1. A high isotope abundance deuterium-labeled gibberellin GA3 compound, characterized in that: The molecular formula of this compound is C 19 H 20 D2O6, the structural formula is:

2. The method for preparing a high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 1, wherein: The steps include: 1) Dissolve compound I in an organic solvent: 2) Add a base and a silicon etherification reagent to an organic solvent, stir and react for 1 h to 45 h, and recrystallize to obtain compound II: 3) Compound II was dissolved in an organic solvent, an organic base was added, ozone was introduced at -40°C to 20°C, and the mixture was stirred for 1h to 15h. Compound III was obtained by recrystallization: 4) Compound III is dissolved in a deuterated solvent, an organic base is added, and the reaction is carried out for 1 to 30 hours. Compound IV is obtained by recrystallization: 5) Compound V was dissolved in an organic solvent, and a base was added under ice-cooling and stirred for 10 min. Compound IV was added and reacted for 1 h to 18 h. Compound VI was obtained by recrystallization: 6) Compound VI was dissolved in an organic solvent, acid was added, and the mixture was stirred for 1 to 28 hours. Compound VII was obtained by recrystallization, i.e., a high isotope abundance deuterium-labeled gibberellin GA3 compound:

3. The method for preparing a high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 2, wherein: The organic solvent in steps 1) and 2) is N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone; the base is triethylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine, cesium carbonate, potassium carbonate or sodium carbonate; the silicon etherification agent is trimethylchlorosilane, tert-butyldimethylchlorosilane, triisopropylchlorosilane or tert-butyldiphenylchlorosilane; and the reaction temperature during stirring is 5°C to 40°C.

4. The method for preparing a high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 3, wherein: The organic solvent is N,N-dimethylformamide or N,N-dimethylacetamide; the base is potassium carbonate or cesium carbonate; and the silicon etherification agent is tert-butyldiphenylchlorosilane.

5. The method for preparing a high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 2, wherein: In the step 3), the organic solvent is diethyl ether, tetrahydrofuran, 1,4-dioxane, dichloromethane or chloroform; the organic base is triethylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine or pyridine; the molar ratio of the compound II to the organic base is 1:0.1 to 1:5.3; and the reaction temperature during stirring is -40°C to 20°C.

6. The method for preparing the high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 5, wherein: The organic solvent is ether, tetrahydrofuran, dichloromethane or chloroform; the organic base is 4-dimethylaminopyridine or pyridine; the molar ratio of the compound II to the organic base is 1:0.1 to 1:5.0; the reaction temperature during stirring is -40°C to 15°C, and the reaction time is 1h to 13h.

7. The method for preparing a high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 2, wherein: In the step 4), the deuterated solvent is a mixed solvent of one of methanol-OD, ethanol-OD, and isopropanol-OD and deuterated water; the organic base is triethylamine, N,N-diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, or 4-dimethylaminopyridine; and the reaction temperature is 10°C to 80°C.

8. The method for preparing the high isotopic abundance deuterium-labeled gibberellin GA3 compound according to claim 7, wherein: The deuterated solvent is a mixed solvent formed by isopropyl alcohol-OD and deuterated water; the organic base is triethylamine, N,N-diisopropylethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene; the reaction temperature is 20°C to 80°C, and the reaction time is 3h to 30h.

9. The method for preparing the high isotopic abundance deuterium-labeled gibberellin GA3 compound according to claim 2, wherein: In the step 5), the organic solvent is diethyl ether, tetrahydrofuran or ethylene glycol dimethyl ether; the base is lithium bistrimethylsilylamide, n-butyl lithium, sodium hydride, potassium tert-butoxide, sodium tert-butoxide or lithium diisopropylamide; and the reaction temperature is 0-50°C.

10. The method for preparing the high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 9, characterized in that: The organic solvent is diethyl ether or ethylene glycol dimethyl ether; the base is lithium bis(trimethylsilyl)amide, n-butyl lithium, sodium hydride or lithium diisopropylamide; the reaction temperature is 0-45° C., and the reaction time is 1 h-16 h.

11. The method for preparing a high-isotope-abundance deuterium-labeled gibberellin GA3 compound according to claim 2, wherein: In step 6), the organic solvent is a mixed solvent of diethyl ether, methyl tert-butyl ether, tetrahydrofuran or 1,4-dioxane and water; the acid is formic acid, acetic acid, propionic acid, pivalic acid, hydrochloric acid or sulfuric acid; and the reaction temperature is -10°C to 60°C.

12. The method for preparing a high-isotope-abundance deuterium-labeled gibberellin GA3 compound according to claim 11, characterized in that: The organic solvent is a mixed solvent formed by tetrahydrofuran or 1,4-dioxane and water; the acid is acetic acid or pivalic acid; the reaction temperature is -10°C to 45°C, and the reaction time is 1h to 25h.

13. Use of the high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 1 as a standard sample in gibberellin GA3 drug quality control and in pharmacological research.

14. The use of the high isotope abundance deuterium-labeled gibberellin GA3 compound according to claim 13, characterized in that: Isotope dilution mass spectrometry was used with a high isotopic abundance deuterated gibberellin GA3 compound as a standard.

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