CN114605483B - Preparation process of icariside I - Google Patents
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- CN114605483B CN114605483B CN202210357981.XA CN202210357981A CN114605483B CN 114605483 B CN114605483 B CN 114605483B CN 202210357981 A CN202210357981 A CN 202210357981A CN 114605483 B CN114605483 B CN 114605483B
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- IYCPMVXIUPYNHI-UHFFFAOYSA-N Icariside I Natural products C1=CC(OC)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 IYCPMVXIUPYNHI-UHFFFAOYSA-N 0.000 title claims abstract description 61
- IYCPMVXIUPYNHI-WPKKLUCLSA-N 3,5-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 IYCPMVXIUPYNHI-WPKKLUCLSA-N 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229930182721 icariside Natural products 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 11
- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 claims description 9
- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 claims description 9
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 12
- 239000002904 solvent Substances 0.000 abstract description 9
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 5
- 235000011149 sulphuric acid Nutrition 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000004809 thin layer chromatography Methods 0.000 description 18
- 239000012265 solid product Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 8
- 229940125904 compound 1 Drugs 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- TUUXBSASAQJECY-UHFFFAOYSA-N 3,5,7-trihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C(CC=C(C)C)=C2O1 TUUXBSASAQJECY-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000893536 Epimedium Species 0.000 description 2
- CTGVBHDTGZUEJZ-UHFFFAOYSA-N Noricaritin Natural products CC(C)(O)CCC1=C(O)C=C(O)C(C(C=2O)=O)=C1OC=2C1=CC=C(O)C=C1 CTGVBHDTGZUEJZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 235000018905 epimedium Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 241000133570 Berberidaceae Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- NGMYNFJANBHLKA-SENBMHEBSA-N Icariside II Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O)c(C/C=C(\C)/C)c3O2)cc1 NGMYNFJANBHLKA-SENBMHEBSA-N 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010041497 Spermatorrhoea Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000020696 epimedium extract Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000017561 flaccidity Diseases 0.000 description 1
- 150000002214 flavonoid derivatives Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- NGMYNFJANBHLKA-LVKFHIPRSA-N icariside II Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O)C(CC=C(C)C)=C2O1 NGMYNFJANBHLKA-LVKFHIPRSA-N 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 230000009818 osteogenic differentiation Effects 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The application discloses a preparation process of icariside I in the technical field of medicine preparation processes, which comprises the steps of taking icariside as a reaction raw material, taking anhydrous lower alcohol as a reaction solvent, taking a proper amount of 98% concentrated H2SO4 as a catalyst, and reacting for a proper time at a proper reaction temperature to obtain the icariside I. The raw materials, the reagents and the solvent adopted in the preparation process are all conventional synthetic reagents, and the cost is low and the solvent is easy to obtain; the reaction conditions of each step are mild, the post-treatment operation is simple, the reaction yield is higher, and the purity of the product is high. The whole preparation cost of the product is low, and the product meets the industrial production requirement.
Description
Technical Field
The invention relates to the technical field of medicine preparation processes, in particular to a preparation process of icariside I.
Background
Herba Epimedii is a traditional Chinese medicine, and is of the genus Epimedium of berberidaceae, and has pungent and sweet taste and warm nature, and can be used as medicine for treating sexual impotence, spermatorrhea, deficiency of kidney-yang, rheumatalgia, flaccidity of tendons and bones, numbness, contracture, etc. Modern pharmacological research proves that the main active ingredients of the epimedium extract comprise a plurality of epimedium flavonoid derivatives such as icariin, icariside and the like. In addition, after oral administration of icariside, various metabolites such as icariside I, icariside II, icaritin and the like are produced in vivo, wherein the chemical formulas of icariside and icariside I are as follows:
the chemical formula of icariin is shown in formula 1, and the chemical formula of icariside I is shown in formula 2
Research shows that icariside I has better pharmacological activities of promoting bone marrow mesenchymal stem cell osteogenic differentiation, resisting tumor and the like compared with the original medicine icariside. In order to be able to prepare icariside I, pharmaceutical researchers have tried to perform hydrolysis reaction on icariside, and the methods reported in the literature mainly involve methods of enzyme catalysis and acid-enzyme mixed catalysis.
As author Yi Peng reports "a preparation method of icaritin" in "Chinese medicinal materials", a preparation method of icariside I is reported herein, and the chemical reaction formula is as follows:
the specific preparation process comprises the following steps: 1g of icariin, 75mL of ethanol and 75mL of 5% dilute sulfuric acid are sequentially added into a 250mL round bottom flask; the reaction mixture was stirred at 50℃for 24 hours and then filtered with a Buchner funnel. The solid filter residue is separated by a silica gel column to obtain 243mg of icariside I, but the yield of the preparation process is only 31%, and in the discussion part of the document, the authors further indicate that the yield of acidolysis intermediate icariside I is only about 30%, and the product is difficult to purify and separate. The preparation process reported in the document has the problems that the yield of the target product is low, and the product is difficult to separate and purify.
Therefore, the application provides a preparation process of icariside I, so as to solve the problems that the yield of a target product is low and the product is difficult to separate and purify in the existing preparation process.
Disclosure of Invention
The invention aims to provide a preparation process of icariside I, which has the advantages of higher reaction yield, high product purity, low overall preparation cost of the product and meeting the requirements of industrial production.
In order to achieve the above purpose, the present invention provides the following technical solutions: the preparation process of icariside I includes the reaction of icariside I in the presence of anhydrous lower alcohol as reaction solvent and 98% concentration H2SO4 as catalyst at proper reaction temperature for proper time to obtain icariside I, and the synthesis process includes the following steps:
the icariside I preparation process of the present invention is a preferable embodiment, wherein the anhydrous lower alcohol includes, but is not limited to, anhydrous methanol, anhydrous ethanol, anhydrous propanol or anhydrous isopropanol, preferably, anhydrous methanol or anhydrous ethanol
In the preparation process of icariside I, a preferable implementation mode, wherein the proper amount of the 98% concentrated H2SO4 catalyst is 1-100 equivalent of the reaction raw material. Preferably 3 to 100 equivalents. More preferably 5 to 25 equivalents.
In a preferred embodiment of the preparation process of icariside I, the reaction temperature is at least 40 ℃ and the reaction solvent is at most reflux temperature. Preferably from 40℃to 80 ℃. More preferably 50 to 70 ℃.
In a preferred embodiment of the process for preparing icariside I according to the present invention, the suitable reaction time is 1 to 12 hours, preferably 1 to 5 hours. More preferably 1 to 3 hours.
The invention has the advantages that: the raw materials, the reagents and the solvent adopted in the preparation process are all conventional synthetic reagents, so that the preparation method is low in cost and easy to obtain; the reaction conditions of each step are mild, the post-treatment operation is simple, the reaction yield is higher, and the purity of the product is high. The whole preparation cost of the product is low, and the product meets the industrial production requirement.
Detailed Description
The following is a further detailed description of the embodiments:
in the examples below, unless otherwise indicated, the test methods described are generally carried out under conventional conditions or conditions recommended by the manufacturer; the raw materials and reagents shown can be obtained by the way of commercial purchase
Example 1: preparation of Compound 1 (icariside I) icariside (100 mg,0.15 mmol) was weighed into a round bottom flask, 4mL of absolute ethyl alcohol was added, 98% concentrated sulfuric acid (0.04 mL,5 equiv.) was added under stirring, after stirring at room temperature for 10 minutes, the reaction flask was put into an oil bath at 60℃and heated, at this time, the reaction solution became clear, the reaction was continued, a yellow solid was gradually precipitated in the reaction solution, after 1 hour, TLC thin layer chromatography showed that the substrate icariside had been completely converted into the target product, the reaction was stopped, the solvent was removed under reduced pressure, the remaining solid product was washed with distilled water, suction filtration and oven drying to obtain a yellow solid product of icariside I (74.5 mg, 95%). m.252-253 ℃ 1H NMR (400 mhz, dmso-d 6) δ=12.41 (s, 1H), 9.61 (s, 1H), 8.12 (d, j=8.8 hz, 2H), 7.10 (d, j=8.9 hz, 2H), 6.57 (s, 1H), 5.33 (d, j=4.4 hz, 1H), 5.17 (t, j=7.2 hz, 1H), 5.12 (d, j=3.8 hz, 1H), 5.05 (d, j=5.3 hz, 1H), 4.97 (d, j=6.8 hz, 1H), 4.62 (t, j=5.6 hz, 1H), 3.81 (s, 3H), 3.65 (ddd, j=21.9, 12.9,6.5hz, 2H), 3.48-3.40 (m, 2H), 3.38 (d, j=6.9 hz, 1H), 3.37 hz, 3.37H), 4.97 (d, j=6.37 hz, 1H), 4.62 (d, j=3.37 hz, 1H), 3.37 (d, 37H).
Consistent with the reference, LC-MS 369 (m+h); HPLC purity 99.5%.
Example 2: preparation of Compound 1 (icariside I) icariside (200 mg,0.30 mmol) was weighed into a round bottom flask, 7mL of absolute methanol was added, 98% of concentrated sulfuric acid (0.08 mL,5 equiv.) was added under stirring, after stirring at normal temperature for 10 minutes, the reaction flask was put into an oil bath at 55deg.C and heated, at this time the reaction solution became clear, the reaction was continued, a yellow solid was gradually precipitated in the reaction solution, and after 2 hours, TLC thin layer chromatography showed that the reaction substrate icariside had been completely converted into the target product. The reaction was stopped, the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the remaining solid product was washed with distilled water, suction-filtered and dried to give a yellow solid product (147.4 mg, 94%) of icariside I. m.p.252-253 ℃.
Example 3: preparation of Compound 1 (icariside I) icariside (50 mg,0.074 mmol) was weighed into a round bottom flask, 5mL of anhydrous isopropanol was added, 98% concentrated sulfuric acid (0.02 mL,5 equiv.) was added under stirring, after stirring at room temperature for 20 minutes, the reaction flask was placed into an oil bath at 60℃and heated, at this time the reaction solution became clear, the reaction was continued, a yellow solid was gradually precipitated in the reaction solution, and after 5 hours, TLC thin layer chromatography showed that the reaction substrate icariside had been completely converted into the target product. The reaction was stopped, the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the remaining solid product was washed with distilled water, suction-filtered and dried to give a yellow solid product (35.3 mg, 90%) of icariside I. m.p.252-253 ℃.
Example 4: preparation of Compound 1 (icariside I) icariside (150 mg,0.22 mmol) was weighed into a round bottom flask, 11ml of ethanol, 11ml of a 5% dilute aqueous H2SO4 solution was added, and stirred at 50℃for 24 hours. TLC thin layer chromatography followed the progress of the reaction, a larger amount of unreacted starting substrate was also present in the reaction solution, and the number of newly obtained product spots was 3. The reaction was stopped, the reaction mixture was cooled to room temperature, ethanol was removed by concentration under reduced pressure, 10mL of saturated brine was added, extraction was performed three times with ethyl acetate (5 mL each time), the ethyl acetate layer was washed twice with saturated aqueous NaHCO3 solution (10 mL each time), 10mL of saturated brine was washed once, and after drying over anhydrous sodium sulfate, icariside I (37.6 mg, 32%) was obtained by column chromatography. m.p.252-253 ℃.
Example 5: icariin (100 mg,0.15 mmol) was weighed into a round bottom flask, 3mL of 2mol/L H SO4 solution and 3mL of ethanol solution were added, the reaction flask was placed into an oil bath at 60℃and heated, a yellow solid gradually precipitated in the reaction solution, and TLC thin layer chromatography after 2.5 hours showed that the substrate icariin disappeared and 3 new spots were produced. To the reaction mixture was added 10mL of saturated brine, and the mixture was extracted three times with ethyl acetate (10 mL each time), and after drying the ethyl acetate layer over anhydrous sodium sulfate, the product of icariside I was obtained by column chromatography as a yellow solid (43.9 mg, 56%). m.p.252-253 ℃.
Example 6: icariin (50 mg,0.074 mmol) was weighed into a round bottom flask, 10ml of 80% HOAc solution was added, the flask was heated in an oil bath at 60℃for 12 hours, and after completion of the reaction, TLC thin layer chromatography showed that there were a small amount of unreacted starting material substrate in the reaction solution and 3 newly obtained product spots. To the reaction solution was added 10mL of saturated brine, and the mixture was extracted three times with ethyl acetate (10 mL each time), and after drying the ethyl acetate layer over anhydrous sodium sulfate, the product of icariside I was obtained by column chromatography as a yellow solid (10.6 mg, 27%). m.p.252-253 ℃.
Example 7: icariin (50 mg,0.074 mmol) was weighed into a round bottom flask, 2mL of isopropanol and 2mL of tetrahydrofuran were added, 98% concentrated sulfuric acid (0.1 mL,25 equiv.) was added under stirring, after stirring at normal temperature for 10 minutes, the reaction flask was placed into an oil bath pot at 60 ℃ and heated, at this time, the reaction solution became clear, the reaction was continued, a yellow solid was gradually precipitated in the reaction solution, and after 4 hours, TLC thin layer chromatography showed that the icariin as a reaction substrate had been completely converted into the target product. The reaction was stopped, the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the remaining solid product was washed with distilled water, suction-filtered and dried to give a yellow solid product (35.3 mg, 90%) of icariside I. m.p.252-253 ℃.
Example 8: preparation of Compound 1 (icariside I) icariside (100 mg,0.15 mmol) was weighed into a round bottom flask, 4mL of absolute ethanol was added, 98% concentrated sulfuric acid (0.2 mL,25 equiv.) was added under stirring, after stirring at normal temperature for 10 minutes, the reaction flask was placed into an oil bath at 60℃and heated, at this time the reaction solution became clear, the reaction was continued, a yellow solid was gradually precipitated in the reaction solution, and after 1 hour, TLC thin layer chromatography showed that the reaction substrate icariside had been completely converted into the target product. The reaction was stopped, the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the remaining solid product was washed with distilled water, suction-filtered and dried to give a yellow solid product (71.3 mg, 91%) of icariside I.
Example 9: preparation of Compound 1 (icariside I) icariside (100 mg,0.15 mmol) was weighed into a round bottom flask, 4mL of absolute ethanol was added, 98% concentrated sulfuric acid (0.8 mL,100 equiv.) was added under stirring, after stirring at normal temperature for 10 minutes, the reaction flask was put into an oil bath at 60℃and heated, at this time the reaction solution became clear, the reaction was continued, after 2.5 hours, TLC thin layer chromatography showed that the substrate icariside disappeared, the target product point was lighter, and there was a very thick point on the base line. The reaction was stopped, the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the remaining solid product was washed with distilled water, suction-filtered and dried to give a yellow solid product (7.8 mg, 10%) of icariside I. m.p.252-253 ℃.
Claims (5)
1. A preparation process of icariside I is characterized in that: icariin is used as a reaction raw material, anhydrous lower alcohol is used as a reaction solvent, and 98% of concentrated H is used 2 SO 4 As a catalyst, icariside I is obtained by reaction, wherein the anhydrous lower alcohol is anhydrous methanol, anhydrous ethanol, anhydrous propanol or anhydrous isopropanol, and the 98% concentration H 2 SO 4 The dosage of the catalyst is 5-20 equivalents of the reaction raw materials; the reaction temperature is 50-70 ℃, the reaction time is 1-10 h,
the synthetic route is as follows:
。
2. the process for preparing icariside I according to claim 1, wherein: the anhydrous lower alcohol is anhydrous methanol or anhydrous ethanol.
3. The process for preparing icariside i according to claim 2, characterized in that: the concentration of the H is 98% 2 SO 4 The catalyst is used in an amount of 5 to 15 equivalents of the reaction raw materials.
4. A process for preparing icariside i according to claim 3, characterized in that: the reaction time is 1 to 5 hours.
5. The process for preparing icariside I according to claim 4, wherein: the reaction time is 1-3 hours.
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Citations (3)
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|---|---|---|---|---|
| WO2002013842A1 (en) * | 2000-08-15 | 2002-02-21 | Hauser, Inc. | Compositions comprising icariside i and anhydroicaritin and methods for making the same |
| CN101113157A (en) * | 2006-07-28 | 2008-01-30 | 上海特化医药科技有限公司 | Isoamylene radical chromocor derivative, preparation method and uses thereof |
| CN106148449A (en) * | 2015-03-24 | 2016-11-23 | 北京珅奥基医药科技有限公司 | A kind of preparation method of icariside I |
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2022
- 2022-04-06 CN CN202210357981.XA patent/CN114605483B/en active Active
Patent Citations (3)
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|---|---|---|---|---|
| WO2002013842A1 (en) * | 2000-08-15 | 2002-02-21 | Hauser, Inc. | Compositions comprising icariside i and anhydroicaritin and methods for making the same |
| CN101113157A (en) * | 2006-07-28 | 2008-01-30 | 上海特化医药科技有限公司 | Isoamylene radical chromocor derivative, preparation method and uses thereof |
| CN106148449A (en) * | 2015-03-24 | 2016-11-23 | 北京珅奥基医药科技有限公司 | A kind of preparation method of icariside I |
Non-Patent Citations (2)
| Title |
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| Synthesis and antimultidrug resistance evaluation of icariin and its derivatives;Dong-Fang Liu et al.;《Bioorganic & Medicinal Chemistry Letters》;第19卷;第4237-4240页 * |
| 淫羊藿苷在不同质子酸催化下的选择性水解反应研究;董维维等;《化学研究与应用》;第34卷(第9期);第2254-2259页 * |
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