Method for catalytic preparation of asarinin by sesamin and application thereof

Abstract

The application provides a method for catalytically preparing asarinin from sesamin and application thereof, and relates to the technical field of organic synthesis.The method comprises the following steps: reacting sesamin under the action of an acid catalyst to obtain asarinin; and the acid catalyst comprises at least one of a heteropoly acid and a salt of the heteropoly acid.The application solves the technical problems of low catalyst activity, low sesamin concentration and low asarinin yield in the prior art, and achieves the technical effects of improving catalyst activity, improving sesamin concentration and improving asarinin yield.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and in particular to a method for catalytically preparing asarinin from sesamin. BACKGROUND

[0002] Asarinin is also known as asarinol, and its molecular formula is C 20 H 18 O6, and its common physical state is flaky or powdery solid. Asarinin is a natural trace compound existing in some medicinal plants, such as asarum herbaceous plants and rutaceae plants. In addition, asarinin is also a by-product in the processing of sesame oil and can be converted from sesamin under specific conditions.

[0003] Asarinin and sesamin are isomers of each other and both belong to fat-soluble lignans. Asarinin has various pharmacological activities, such as anticancer, antibacterial, anti-inflammatory, and immunosuppression, and its pharmacological activity is even stronger than that of sesamin. Therefore, asarinin has wide application prospects in the medical and health fields.

[0004] At present, asarinin is mainly extracted from medicinal plants such as asarum. However, the natural content of asarinin is low, and the extraction efficiency is low and time-consuming, so asarinin cannot be obtained in large quantities. Catalyzing sesamin to asarinin by a chemical method is a relatively efficient preparation route. The catalysts for converting sesamin to asarinin include hydrochloric acid, sulfuric acid, camphor sulfonic acid, phosphoric acid, bromic acid, aluminum trichloride, ferric trichloride, tin chloride, titanium chloride, montmorillonite, molecular sieve, and silicoaluminate, etc. The solvents include methanol, ethanol, acetone, ethyl acetate, and oil, etc. However, the existing catalytic system for converting sesamin to asarinin has two shortcomings: first, the activity of the catalyst is not high enough, so more catalyst needs to be added and a longer reaction time is required; second, the concentration of the raw material sesamin in the catalytic reaction system is too low, which seriously limits the yield of the reaction system.

[0005] In view of this, the present application is proposed. SUMMARY

[0006] One of the purposes of the present application is to provide a method for catalytically preparing asarinin from sesamin, which has the advantages of high catalytic reaction activity and high sesamin concentration, and can improve the yield of asarinin.

[0007] The second purpose of the present application is to provide an application of the method for catalytically preparing asarinin from sesamin.

[0008] In order to achieve the above purposes of the present application, the following technical solutions are adopted:

[0009] In a first aspect, a method for catalytically preparing asarinin from sesamin comprises the following steps:

[0010] The acid catalyst is reacted with the sesamin to obtain the asarinin.

[0011] The acid catalyst comprises at least one of a heteropoly acid and a salt of the heteropoly acid.

[0012] Further, the heteropoly acid comprises a supported heteropoly acid.

[0013] Further, the salt of the heteropoly acid comprises a supported salt of the heteropoly acid.

[0014] Further, the salt of the heteropoly acid comprises at least one of a cesium salt of the heteropoly acid, a silver salt of the heteropoly acid, an ammonium salt of the heteropoly acid, a lithium salt of the heteropoly acid, a sodium salt of the heteropoly acid, and a potassium salt of the heteropoly acid.

[0015] Further, the heteropoly acid comprises at least one of phosphotungstic acid, phosphotungstovanadic acid, phosphomolybdic acid, phosphomolybdovanadic acid, silicotungstic acid, silicotungstovanadic acid, silicomolybdic acid, silicomolybdovanadic acid, germanotungstic acid, borotungstic acid, and cobaltotungstic acid, and is preferably phosphotungstic acid.

[0016] Further, the solvent for the reaction comprises an ether solvent.

[0017] Preferably, the ether solvent comprises at least one of propyl ether, butyl ether, ethyl propyl ether, ethyl butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, 3-methyl tetrahydrofuran, 1,4-dioxane, and 12-crown-4 ether, and is preferably tetrahydrofuran.

[0018] Further, the reaction temperature is 30-120℃, and the reaction time is 1-10h.

[0019] Further, the molar ratio of the acid catalyst to the sesamin is 50:1-1:50.

[0020] In a second aspect, the method described in any one of the above aspects is used in the preparation of a pharmaceutical product.

[0021] Further, the pharmaceutical product comprises at least one of an anticancer product, an antibacterial product, an anti-inflammatory product, and an immunosuppressive product.

[0022] Compared with the prior art, the present application has at least the following beneficial effects:

[0023] The method for catalytically preparing asarinin from sesamin provided by the present application uses a heteropoly acid and / or a salt of the heteropoly acid as an acid catalyst, has the advantage of high catalytic activity, and thus can improve the yield of asarinin. The method for catalytically preparing asarinin from sesamin provided by the present application has the advantage of efficient catalysis, and can effectively improve the yield and yield of asarinin.

[0024] The application provides application of the method for catalytically preparing asarinin from sesamin in preparation of a medicine, and has the same advantages as the method, which will not be repeated here. DETAILED DESCRIPTION

[0025] The technical solutions of the application will be described clearly and completely below with reference to the embodiments. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative efforts belong to the protection scope of the application.

[0026] According to a first aspect of the application, a method for catalytically preparing asarinin from sesamin is provided, comprising the following steps:

[0027] The sesamin is reacted under the action of the acid catalyst to obtain asarinin.

[0028] The acid catalyst comprises at least one of a heteropoly acid and a salt of the heteropoly acid.

[0029] In the application, the specific kind of acid catalyst has a high-activity catalytic effect, can cause the sesamin to undergo epimerization, and then efficiently convert the sesamin into asarinin, so that the asarinin pure product can be obtained by combining a separation and purification method such as chromatography and recrystallization.

[0030] The method for catalytically preparing asarinin from sesamin provided by the application solves the technical problems of low catalyst activity and low asarinin yield in the prior art, and achieves the technical effects of improving the catalyst activity and the asarinin yield.

[0031] In the application, the form of the heteropoly acid and the salt of the heteropoly acid is not particularly limited, for example, the heteropoly acid includes but is not limited to a supported heteropoly acid; the salt of the heteropoly acid includes but is not limited to a supported salt of the heteropoly acid; and the medium for supporting is not particularly limited, for example, the medium can be a molecular sieve, but is not limited thereto. The application can use the supported heteropoly acid and / or the supported salt of the heteropoly acid to catalyze the sesamin to undergo epimerization to obtain asarinin, and the catalytic effect can be improved.

[0032] In a preferred embodiment, the salt of the heteropoly acid in the application includes but is not limited to at least one of a cesium salt of the heteropoly acid, a silver salt of the heteropoly acid, an ammonium salt of the heteropoly acid, a lithium salt of the heteropoly acid, a sodium salt of the heteropoly acid and a potassium salt of the heteropoly acid, which is beneficial to improving the catalytic effect of converting the sesamin into asarinin.

[0033] In a preferred embodiment, the heteropoly acid of the present application includes, but is not limited to, at least one of phosphotungstic acid, phosphotungstovanadic acid, phosphomolybdic acid, phosphomolybdovanadic acid, silicotungstic acid, silicotungstovanadic acid, silicomolybdic acid, silicomolybdovanadic acid, germanotungstic acid, borotungstic acid, and cobaltotungstic acid, which has preferable catalytic activity and can efficiently catalyze the conversion of sesamin into asarinin.

[0034] The acid catalyst of the present application can be further preferably phosphotungstic acid and its salt, wherein the salt of phosphotungstic acid can be, for example, at least one of cesium salt of phosphotungstic acid, silver salt of phosphotungstic acid, ammonium salt of phosphotungstic acid, lithium salt of phosphotungstic acid, sodium salt of phosphotungstic acid, and potassium salt of phosphotungstic acid, but is not limited thereto, which has super strong acidity and thus excellent catalytic activity and can more efficiently catalyze the conversion of sesamin into asarinin.

[0035] Compared with the hydrochloric acid catalyst commonly used in the prior art to catalyze the conversion of sesamin into asarinin, the phosphotungstic acid and its salt are selected as the catalyst for catalyzing sesamin in the present application, and the intrinsic catalytic activity conversion frequency value TOF of the phosphotungstic acid and its salt is about 64 times higher than that of hydrochloric acid, which shows that the phosphotungstic acid and its salt have excellent catalytic activity for the conversion of sesamin.

[0036] In a preferred embodiment, the reaction solvent of the present application can be an ether solvent, which can be, for example, at least one of symmetrical ether and / or asymmetrical ether, wherein the symmetrical ether includes, but is not limited to, at least one of propyl ether and butyl ether, and the asymmetrical ether includes, but is not limited to, at least one of ethyl propyl ether and ethyl butyl ether, and the ether solvent of the present application further includes, but is not limited to, at least one of tetrahydrofuran, 2-methyl tetrahydrofuran, 3-methyl tetrahydrofuran, 1,4-dioxane, and 12-crown-4 ether. According to the principle of similar dissolves similar, the ether solvent can improve the solubility of sesamin, thereby effectively increasing the mass concentration of sesamin in the reaction system, so that sesamin can be fully utilized, and the purpose of greatly increasing the yield of single reaction under the same reaction volume is achieved, and the reactant is saved.

[0037] The ether solvent of the present application can be further preferably tetrahydrofuran, which has very excellent solubility for sesamin, and thus can greatly increase the mass concentration of sesamin in the reaction system, so that sesamin can be more fully utilized, and the yield of asarinin is greatly increased.

[0038] Compared with the ethanol commonly used in the prior art as the solvent of the reaction system, the tetrahydrofuran is selected as the solvent of the sesamin reaction system in the present application, which can increase the mass concentration of sesamin from 0.2% to 20%, which is increased by 100 times, which means that the yield of single reaction will be greatly increased when the volume of the reactor is the same.

[0039] In the present application, the temperature for the reaction of sesamin under the action of the acid catalyst is 30-120℃, and the typical but non-limiting temperature is, for example, 40℃, 50℃, 60℃, 70℃, 80℃, 100℃, 120℃, and the reaction time is 1-10h, and the typical but non-limiting time is, for example, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, which is more favorable to improve the reaction effect of the conversion of sesamin into asarinin, to make the reactants fully utilized, and to further improve the yield and output of the reaction.

[0040] In the present application, the molar ratio of the acid catalyst to sesamin is 50:1-1:50, and the typical but non-limiting molar ratio is, for example, 40:1, 30:1, 20:1, 10:1, 1:1, 1:10, 1:20, 1:30, 1:40, which is more favorable to improve the reaction effect of the catalytic preparation of asarinin from sesamin, and to further improve the yield and output of asarinin.

[0041] The method for the catalytic preparation of asarinin from sesamin provided by the present application has the advantages of high catalytic activity and high conversion rate, and high reaction output.

[0042] According to the second aspect of the present application, the use of the method for the catalytic preparation of asarinin from sesamin in the preparation of a pharmaceutical product is provided.

[0043] The use of the method for the catalytic preparation of asarinin from sesamin in the preparation of a pharmaceutical product provided by the present application has the advantages of high catalytic activity, high conversion rate, and high reaction output.

[0044] The pharmaceutical product includes, but is not limited to, at least one of an anticancer drug, a bacteriostatic drug, an anti-inflammatory drug, and an immunosuppressive drug.

[0045] The present application will be further described by the following examples. Unless otherwise specified, the materials in the examples are prepared according to the existing methods, or directly purchased from the market.

[0046] Example 1

[0047] A method for the catalytic preparation of asarinin from sesamin includes the following steps:

[0048] A flask was charged with 100 g of tetrahydrofuran, 20 g of sesamol and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (66 °C), the stirring was continued under reflux for 1 h, after which the sample was treated and measured by HPLC, the asarinin content was 17.5%.

[0049] Example 2

[0050] A method for the catalytic preparation of asarinin from sesamol, comprising the following steps:

[0051] A flask was charged with 100 g of tetrahydrofuran, 20 g of sesamol and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (66 °C), the stirring was continued under reflux for 1 h, after which the sample was treated and measured by HPLC, the asarinin content was 17.5%.

[0052] Example 3

[0053] A method for the catalytic preparation of asarinin from sesamol, comprising the following steps:

[0054] A flask was charged with 100 g of tetrahydrofuran, 20 g of sesamol and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (66 °C), the stirring was continued under reflux for 1 h, after which the sample was treated and measured by HPLC, the asarinin content was 17.5%.

[0055] Example 4

[0056] A method for the catalytic preparation of asarinin from sesamol, comprising the following steps:

[0057] A flask was charged with 100 g of tetrahydrofuran, 20 g of sesamol and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (66 °C), the stirring was continued under reflux for 1 h, after which the sample was treated and measured by HPLC, the asarinin content was 17.5%.

[0058] Example 5

[0059] A method for the catalytic preparation of asarinin from sesamol, comprising the following steps:

[0060] A flask was charged with 100 g of tetrahydrofuran, 20 g of sesamol and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (66 °C), the stirring was continued under reflux for 1 h, after which the sample was treated and measured by HPLC, the asarinin content was 17.5%.

[0061] Example 6

[0062] A method for catalytic preparation of asarinin from sesamin, comprising the following steps:

[0063] A flask was charged with 100 g of ethyl butyl ether, 20 g of sesamin and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (92°C), continuously stirred under reflux for 1 h, after which the sample liquid was treated and determined by HPLC, the asarinin content was 22.5%.

[0064] Example 7

[0065] A method for catalytic preparation of asarinin from sesamin, comprising the following steps:

[0066] A flask was charged with 100 g of 2-methyl tetrahydrofuran, 20 g of sesamin and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (80°C), continuously stirred under reflux for 1 h, after which the sample liquid was treated and determined by HPLC, the asarinin content was 18.8%.

[0067] Example 8

[0068] A method for catalytic preparation of asarinin from sesamin, comprising the following steps:

[0069] A flask was charged with 100 g of 3-methyl tetrahydrofuran, 20 g of sesamin and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (84°C), continuously stirred under reflux for 1 h, after which the sample liquid was treated and determined by HPLC, the asarinin content was 19.1%.

[0070] Example 9

[0071] A method for catalytic preparation of asarinin from sesamin, comprising the following steps:

[0072] A flask was charged with 100 g of 12-crown-4 ether, 20 g of sesamin and 1.74 mmol of phosphotungstic acid, a condenser was attached, stirred and heated to boiling (70°C / 0.5 mmHg), continuously stirred under reflux for 1 h, after which the sample liquid was treated and determined by HPLC, the asarinin content was 18.2%.

[0073] Example 10

[0074] The difference between this embodiment and Example 1 is that this embodiment uses an equal amount of phosphotungstic acid heteropoly acid to replace the phosphotungstic acid of Example 1, and the rest is the same as Example 1, and the asarinin content is 14.3%.

[0075] Example 11

[0076] The difference between this embodiment and embodiment 2 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 2, and the rest is the same as embodiment 2, and the content of asarinin generated is 15.0%.

[0077] Embodiment 12

[0078] The difference between this embodiment and embodiment 2 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 2, and the rest is the same as embodiment 2, and the content of asarinin generated is 15.0%.

[0079] Embodiment 13

[0080] The difference between this embodiment and embodiment 3 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 3, and the rest is the same as embodiment 3, and the content of asarinin generated is 16.1%.

[0081] Embodiment 14

[0082] The difference between this embodiment and embodiment 3 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 3, and the rest is the same as embodiment 3, and the content of asarinin generated is 16.1%.

[0083] Embodiment 15

[0084] The difference between this embodiment and embodiment 4 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 1, and the rest is the same as embodiment 4, and the content of asarinin generated is 24.1%.

[0085] Embodiment 16

[0086] The difference between this embodiment and embodiment 4 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 4, and the rest is the same as embodiment 4, and the content of asarinin generated is 24.4%.

[0087] Embodiment 17

[0088] The difference between this embodiment and embodiment 5 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 5, and the rest is the same as embodiment 5, and the content of asarinin generated is 13.2%.

[0089] Embodiment 18

[0090] The difference between this embodiment and embodiment 6 is that this embodiment uses phosphomolybdic acid of equal amount of substance to replace phosphotungstic acid of embodiment 6, and the rest is the same as embodiment 6, and the content of asarinin generated is 17.7%.

[0091] Embodiment 19

[0092] The difference between this embodiment and embodiment 7 is that this embodiment uses the same amount of cobalt tungstate to replace the phosphotungstic acid in embodiment 7, and the rest is the same as embodiment 7, and the content of asarinin generated is 14.7%.

[0093] Embodiment 20

[0094] The difference between this embodiment and embodiment 8 is that this embodiment uses the same amount of cesium phosphotungstate to replace the phosphotungstic acid in embodiment 8, and the rest is the same as embodiment 8, and the content of asarinin generated is 20.0%.

[0095] Embodiment 21

[0096] The difference between this embodiment and embodiment 9 is that this embodiment uses mesoporous SBA-15 molecular sieve loaded phosphotungstic acid (the amount of loaded phosphotungstic acid is 1.74 mmol) to replace the phosphotungstic acid in embodiment 9, and the rest is the same as embodiment 9, and the content of asarinin generated is 12.1%.

[0097] Embodiment 22

[0098] A flask is added with 100 g of anhydrous ethanol, 0.2 g of sesamin and 1.74 mmol of phosphotungstic acid, a condenser is connected, stirring and heating to boiling (78°C), continuous stirring and keeping anhydrous ethanol boiling under reflux state, reaction for 1 h, then the sample liquid is treated and measured by HPLC, the content of asarinin generated is 20.7%.

[0099] Embodiment 23

[0100] A flask is added with 100 g of anhydrous ethanol, 0.2 g of sesamin and 1.74 mmol of cesium phosphotungstate, a condenser is connected, stirring and heating to boiling (78°C), continuous stirring and keeping anhydrous ethanol boiling under reflux state, reaction for 1 h, then the sample liquid is treated and measured by HPLC, the content of asarinin generated is 21.5%.

[0101] Embodiment 24

[0102] A flask is added with 100 g of anhydrous ethanol, 0.2 g of sesamin and 1.74 mmol of phosphomolybdic acid, a condenser is connected, stirring and heating to boiling (78°C), continuous stirring and keeping anhydrous ethanol boiling under reflux state, reaction for 1 h, then the sample liquid is treated and measured by HPLC, the content of asarinin generated is 18.6%.

[0103] Embodiment 25

[0104] A flask was charged with 100 g of absolute ethanol, 0.2 g of sesame oil, and 1.74 mmol of tungstophosphoric acid, fitted with a condenser, stirred, and heated to boiling (78 °C). The stirring was continued under reflux and the absolute ethanol was kept boiling for 1 h. After that, the sample was treated and analyzed by HPLC, and the content of asarinin was 15.1%.

[0105] Example 26

[0106] A flask was charged with 100 g of absolute ethanol, 0.2 g of sesame oil, and 1.74 mmol of tungstophosphoric acid, fitted with a condenser, stirred, and heated to boiling (78 °C). The stirring was continued under reflux and the absolute ethanol was kept boiling for 1 h. After that, the sample was treated and analyzed by HPLC, and the content of asarinin was 15.1%.

[0107] Example 27

[0108] A flask was charged with 100 g of absolute ethanol, 0.2 g of sesame oil, and 1.74 mmol of tungstophosphoric acid, fitted with a condenser, stirred, and heated to boiling (78 °C). The stirring was continued under reflux and the absolute ethanol was kept boiling for 1 h. After that, the sample was treated and analyzed by HPLC, and the content of asarinin was 15.1%.

[0109] Example 28

[0110] A flask was charged with 100 g of absolute ethanol, 0.2 g of sesame oil, and 1.74 mmol of tungstophosphoric acid, fitted with a condenser, stirred, and heated to boiling (78 °C). The stirring was continued under reflux and the absolute ethanol was kept boiling for 1 h. After that, the sample was treated and analyzed by HPLC, and the content of asarinin was 15.1%.

[0111] Comparative Example 1

[0112] The difference between this comparative example and Example 1 is that this comparative example uses sulfuric acid instead of tungstophosphoric acid in Example 1, and the amount of sulfuric acid added is 1.74 mmol. The rest is the same as Example 1, and the content of asarinin is 16.8%.

[0113] Comparative Example 2

[0114] The difference between this comparative example and Example 1 is that this comparative example uses phosphoric acid instead of tungstophosphoric acid in Example 1, and the amount of phosphoric acid added is 1.74 mmol. The rest is the same as Example 1, and the content of asarinin is 1.4%.

[0115] Comparative Example 3

[0116] The flask is added with 100 g of anhydrous ethanol, 0.2 g of sesamin and 100 mmol of hydrochloric acid, a condenser is connected, stirring and heating to boiling (78℃), continuously stirring and keeping anhydrous ethanol boiling under reflux state, reaction for 1 h, then the sample liquid is treated and determined by HPLC, the asarinin content is 18.5%.

[0117] From the above examples 1-28 and comparative examples 1-3, it can be seen that the method for catalytically preparing asarinin by using sesamin provided by the present application has the advantages of high catalytic reaction activity by using heteropoly acid and / or salt of heteropoly acid as an acid catalyst, and high yield by using ether solvent as the solvent of the reaction system according to the principle of similar solubility, which can improve the solubility of sesamin, the mass concentration in the reaction system and the yield. Therefore, the method for catalytically preparing asarinin by using sesamin provided by the present application can effectively improve the yield and the production of asarinin, and save the use of catalyst.

[0118] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the present application, but not to limit it; although the present application has been described in detail with reference to the above examples, those skilled in the art should understand that: it can still modify the technical solutions recorded in the above examples, or make equivalent replacement for part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A process for the catalytic preparation of asarinin from sesamin, characterized in that, The method comprises the following steps: The sesamin is reacted under the action of an acid catalyst to obtain asarinin; The acid catalyst is phosphotungstic acid. The solvent of the reaction is butyl ether.

2. The method of claim 1, wherein, The molar ratio of the acid catalyst to sesamin is 50:1-1:50.