Cannabidiol-3-sulfonic acid, preparation method and application thereof, and cannabidiol derivative
阅读说明：本技术 一种大麻二酚-3-磺酸及其制备方法和应用、大麻二酚衍生物 (Cannabidiol-3-sulfonic acid, preparation method and application thereof, and cannabidiol derivative ) 是由 曲桂武 崔明 于 2019-08-28 设计创作，主要内容包括：本发明属于医药化工技术领域,尤其涉及一种大麻二酚-3-磺酸及其制备方法和应用、大麻二酚衍生物。本发明在大麻二酚的分子结构中引入磺酸基,磺酸基作为极性基团,能够增加大麻二酚的极性,从而提高其水溶性,所述大麻二酚-3-磺酸可与无机碱或有机碱发生成盐反应,进一步增加大麻二酚的水溶性,并且可增大基于CBD结构母核与生理活性的药物的成药性；此外,在保证大麻二酚基本结构母核不发生大的变化的前提下,本发明提供的大麻二酚-3-磺酸中新引入的磺酸基可以作为新的作用位点与特定基团反应,进一步拓宽了大麻二酚-3-磺酸的研究与应用范围。(The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to cannabidiol-3-sulfonic acid, a preparation method and application thereof, and a cannabidiol derivative. According to the invention, a sulfonic group is introduced into a molecule structure of cannabidiol, the sulfonic group is used as a polar group, so that the polarity of the cannabidiol can be increased, the water solubility of the cannabidiol can be improved, the cannabidiol-3-sulfonic acid can be subjected to a salt forming reaction with inorganic base or organic base, the water solubility of the cannabidiol is further increased, and the druggability of a medicine based on a CBD structure mother nucleus and physiological activity can be increased; in addition, on the premise of ensuring that the basic structure mother nucleus of the cannabidiol is not changed greatly, the sulfonic group newly introduced into the cannabidiol-3-sulfonic acid provided by the invention can be used as a new action site to react with a specific group, so that the research and application range of the cannabidiol-3-sulfonic acid is further widened.)
1. Cannabidiol-3-sulfonic acid, characterized by having the structure shown in formula I:
2. a process for the preparation of cannabidiol-3-sulfonic acid as claimed in claim 1, comprising the steps of:
the cannabidiol is mixed with concentrated sulfuric acid for sulfonation reaction to obtain cannabidiol-3-sulfonic acid.
3. The method according to claim 2, wherein the molar ratio of cannabidiol to concentrated sulfuric acid is 1:15 to 30.
4. The preparation method according to claim 2, wherein the temperature of the sulfonation reaction is 0 to 35 ℃ and the time is 2 to 8 hours.
5. The method of claim 2, further comprising, after the sulfonation reaction is completed: extracting the obtained reaction liquid, and then purifying the material obtained by extraction.
6. The method of claim 5, wherein the purification comprises column chromatography and crystallization sequentially.
7. The preparation method as claimed in claim 6, wherein the chromatography medium for column chromatography comprises silica gel, octadecyl bonded silica gel, macroporous adsorbent resin or polyamide.
8. The method according to any one of claims 5 to 7, wherein the solvent used for the extraction, column chromatography and crystallization independently comprises water, ethanol, methanol, ethyl acetate or petroleum ether.
9. Use of cannabidiol-3-sulfonic acid as claimed in claim 1 in the preparation of cannabidiol derivatives wherein the sulfonic acid group of the cannabidiol-3-sulfonic acid acts as a reaction site.
10. Cannabidiol derivatives prepared for use as claimed in claim 9, comprising cannabidiol-3-sulphonate and cannabidiol-3-sulphonamide.
Technical Field
The invention relates to the technical field of pharmaceutical chemicals, in particular to a cannabidiol derivative, a preparation method and application thereof, and a cannabidiol derivative.
Background
Cannabidiol (CBD), also known as levo-trans-cannabidiol; the english name is (-) -canabidiol; the name of Chinese culture is 2- [ (1R, 6R) -3-methyl-6- (1-methylethenyl) -2-cyclohexene-1-yl]-5-pentyl-1, 3-benzenediol; chemical name of English: 2- [ (1R, 6R) -3-methyl-6- (1-methyhethyl) -2-cyclohexen-1-yl]-5-penthyl-1, 3-benzandiol; the molecular formula is as follows: c21H30O2(ii) a Molecular weight: 314.46, respectively; CAS accession number: 13956-29-1.
Cannabidiol (CBD) is one of the main phenolic chemical components in cannabis, and in vivo experiments show that CBD can not only antagonize the mental activity caused by THC agonizing cannabinoid I type receptor (CB1R), but also has the effects of anticonvulsant, sedative hypnotic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective, and is a natural active component with great application prospects in the fields of medicine and food.
In recent years, studies on the physiological activity and development of applications of CBD have been advanced. UK GW pharmaceutical company has developed Sative (oral mucosa spray with THC/CBD content ratio of 1) and Epidiolex (liquid formulation of CBD) two drugs for the treatment of Tuberous Sclerosis (TSC) and seizure epilepsy in children, respectively. AXIM (R) Biotech has also entered clinical trials for the treatment of irritable bowel syndrome using cannabidiol-containing chewing gum. In addition, CBD has been developed in the fields of foods, cosmetics, and the like.
Currently, the field of application research of CBD is mainly focused on drug development. The high-purity CBD is a white or light yellow crystal, has a melting point of 66-67 ℃, is hardly dissolved in water or a 10% sodium hydroxide solution, and is easily dissolved in organic solvents such as ethanol, methanol, diethyl ether, benzene, chloroform, petroleum ether and the like. This ester-soluble nature of CBD has made it a great limitation in drug development.
In view of the clinical need of medicines with faster absorption and higher bioavailability for certain specific diseases, the water solubility of the CBD is improved, and the CBD has important scientific research value and social value.
Disclosure of Invention
The invention aims to provide cannabidiol-3-sulfonic acid, a preparation method and application thereof, and a cannabidiol derivative, wherein the cannabidiol-3-sulfonic acid has high water solubility.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides cannabidiol-3-sulfonic acid which has a structure shown in a formula I:
the invention provides a preparation method of cannabidiol-3-sulfonic acid in the technical scheme, which comprises the following steps:
the cannabidiol is mixed with concentrated sulfuric acid for sulfonation reaction to obtain cannabidiol-3-sulfonic acid.
The invention provides a preparation method of cannabidiol-3-sulfonic acid in the technical scheme, which comprises the following steps:
the cannabidiol is mixed with concentrated sulfuric acid for sulfonation reaction to obtain cannabidiol-3-sulfonic acid.
Preferably, the molar ratio of the cannabidiol to the concentrated sulfuric acid is 1: 15-30.
Preferably, the temperature of the sulfonation reaction is 0-35 ℃ and the time is 2-8 h.
Preferably, after the sulfonation reaction is completed, the method further comprises: extracting the obtained reaction liquid, and then purifying the material obtained by extraction.
Preferably, the purification method comprises column chromatography and crystallization sequentially.
Preferably, the chromatography medium used for column chromatography comprises silica gel, octadecyl bonded silica gel, macroporous adsorption resin or polyamide.
Preferably, the solvent used for the extraction, column chromatography and crystallization independently comprises water, ethanol, methanol, ethyl acetate or petroleum ether.
The invention provides an application of the cannabidiol-3-sulfonic acid in the technical scheme in preparation of cannabidiol derivatives, wherein sulfonic groups in the cannabidiol-3-sulfonic acid are used as reaction sites.
The invention provides a cannabidiol derivative prepared by the application of the technical scheme, which comprises cannabidiol-3-sulfonate and cannabidiol-3-sulfonamide.
The invention provides cannabidiol-3-sulfonic acid, sulfonic groups are introduced into the molecular structure of cannabidiol, and the sulfonic groups are used as polar groups, so that the polarity of cannabidiol can be increased, and the water solubility of cannabidiol is further improved;
the cannabidiol-3-sulfonic acid can be subjected to salt forming reaction with inorganic base or organic base, so that the obtained cannabidiol-3-sulfonate has better water solubility, the water solubility of the cannabidiol derivative can be further increased, and the druggability of a medicine based on a CBD structure mother nucleus and physiological activity is increased;
in addition, on the premise of ensuring that the basic structure mother nucleus of the cannabidiol is not changed greatly, the sulfonic group newly introduced into the cannabidiol-3-sulfonic acid provided by the invention can be used as a new action site to react with a specific group, so that the research and application range of the cannabidiol-3-sulfonic acid can be further widened.
Drawings
FIG. 1 is a hydrogen spectrum of cannabidiol-3-sulfonic acid prepared in example 1;
FIG. 2 is a hydrogen spectrum of cannabidiol-3-sulfonamide prepared in example 4.
Detailed Description
The invention provides cannabidiol-3-sulfonic acid which has a structure shown in a formula I:
in the present invention, the chemical name of cannabidiol-3-sulfonic acid is fully known as: (1' R,2' R) -2, 6-dihydroxy-5 ' -methyl-4-pentyl-2 "- (prop-1-en-2-yl) -1", 2',3',4' -tetrahydro- [1,1' -biphenyl ] -3-sulfonic acid. In the cannabidiol-3-sulfonic acid provided by the invention, the sulfonic group is introduced into the structure of the cannabidiol as a polar group, so that the polarity of the cannabidiol can be enhanced, and the water solubility of the cannabidiol is further increased.
The invention provides a preparation method of cannabidiol-3-sulfonic acid in the technical scheme, which comprises the following steps:
the cannabidiol is mixed with concentrated sulfuric acid for sulfonation reaction to obtain cannabidiol-3-sulfonic acid.
In the present invention, unless otherwise specified, all the starting materials required for the preparation are commercially available products well known to those skilled in the art.
The invention mixes cannabidiol with concentrated sulfuric acid to carry out sulfonation reaction, thus obtaining cannabidiol-3-sulfonic acid. In the present invention, the concentrated sulfuric acid is preferably a commercially available concentrated sulfuric acid, i.e., a concentrated sulfuric acid with a mass fraction of 98%.
In the invention, the molar ratio of the cannabidiol to the concentrated sulfuric acid is preferably 1: 15-30, and more preferably 1: 20-25. In the present invention, the mixing process is preferably: adding concentrated sulfuric acid into a three-neck flask, cooling to 0 ℃ in an ice water bath, adding cannabidiol, controlling the temperature to be lower than 15-25 ℃, and finishing mixing after the addition.
In the invention, the temperature of the sulfonation reaction is preferably 0-35 ℃, more preferably 10-30 ℃, most preferably 15-25 ℃, and the time is preferably 2-8 hours, more preferably 3-6 hours, most preferably 4-5 hours. In the sulfonation reaction process, sulfonic groups on concentrated sulfuric acid are introduced into a cannabidiol structure to obtain cannabidiol-3-sulfonic acid with sulfonic groups.
In the present invention, after the sulfonation reaction is completed, it is preferable to further include: extracting the obtained reaction liquid, and then purifying the material obtained by extraction. In the present invention, the extraction is preferably carried out in an ice-water bath. After the extraction is finished, purifying an organic phase obtained by the extraction; the purification method preferably comprises column chromatography and crystallization, which are performed sequentially.
In the present invention, the chromatography medium used for the column chromatography preferably comprises silica gel, octadecyl bonded silica gel, macroporous adsorption resin or polyamide; the solvent used for the extraction, column chromatography and crystallization preferably independently comprises water, ethanol, methanol, ethyl acetate or petroleum ether. The specific process of the column chromatography is not particularly limited in the invention, and the process known to those skilled in the art can be selected.
In the embodiment of the invention, when silica gel is used for column chromatography, specifically, the organic phase obtained by extraction is subjected to reduced pressure concentration at 50 ℃, then is applied to a 200-300-mesh silica gel column, an eluant 1 (petroleum ether: ethyl acetate: methanol: 8:1:1) is used for eluting 2-3 column volumes, an eluant 2 (petroleum ether: ethyl acetate: methanol: 4:1:2) is used for eluting 2-3 column volumes, an eluant 2 elution part is collected, after reduced pressure drying, a proper amount of methanol is added at room temperature until all solids are dissolved, the mixture is kept at room temperature, natural volatilization is carried out until crystallization appears, and then the mixture is kept at 5-10 ℃ for 2-5 h, so that the diphenol hemp-3-sulfonic acid is obtained.
In the embodiment of the invention, when macroporous adsorption resin is adopted for column chromatography, specifically, an organic phase obtained by extraction is decompressed and dried at 50 ℃ and then dissolved in 10% ethanol solution, the organic phase is loaded on an AB-8 type macroporous adsorption resin column, the column is washed by 10% ethanol for 3-5 column volumes, then is washed by 50% ethanol for 2-3 column volumes, and finally is washed by 95% ethanol for 2-3 column volumes; collecting 50% ethanol elution part, drying under reduced pressure, adding appropriate amount of anhydrous ethanol until solid is completely dissolved, standing at room temperature, naturally volatilizing solvent until crystallization appears, and standing at 5-10 deg.C for 2-5 h to obtain cannabidiol-3-sulfonic acid.
The invention provides an application of the cannabidiol-3-sulfonic acid in the technical scheme in preparation of cannabidiol derivatives, wherein sulfonic groups in the cannabidiol-3-sulfonic acid are used as reaction sites. In the invention, the sulfonic group introduced into the cannabidiol-3-sulfonic acid can be used as a new chemical action site, and the preparation of a new cannabidiol derivative can be carried out on the premise of not greatly changing the molecular structure of cannabidiol.
In an embodiment of the present invention, the cannabidiol-3-sulfonic acid may be used to prepare a cannabidiol-3-sulfonate (e.g. sodium cannabidiol-3-sulfonate), the method of preparation preferably comprising the steps of:
pouring the reaction solution obtained by the sulfonation reaction in the technical scheme into a saturated NaCl solution (20 times volume), salting out, carrying out suction filtration on the obtained precipitate, washing the precipitate with the saturated NaCl solution until the precipitate is nearly neutral, dissolving the obtained filter cake in hot water, adjusting the pH value to be neutral, filtering the solution while the solution is hot, and refrigerating the solution at the temperature of 5-10 ℃ to obtain the cannabidiol-3-sodium sulfonate (colorless crystal). In the invention, the mass ratio of the hot water to the filter cake is preferably 5:1, and the temperature of the hot water is preferably 70-90 ℃. In the present invention, the base used for adjusting pH preferably includes an inorganic base or an organic base, and more preferably NaOH, Ca (OH)2、Mg(OH)2Ethanolamine or pyridine; the alkali is preferably used in the form of solution, the mass fraction of the alkali solution is not particularly limited, and the alkali solution can be adjusted by a person skilled in the art according to actual requirements; in the examples of the present invention, the NaOH solution is preferably used in a mass fraction of 10%.
In the invention, the cannabidiol-3-sodium sulfonate can be acidified by equimolar hydrochloric acid and extracted by ethyl acetate to obtain cannabidiol-3-sulfonic acid, namely, the cannabidiol-3-sulfonic acid and the cannabidiol-3-sulfonate can be mutually converted. The acidification with hydrochloric acid and the extraction with ethyl acetate are not particularly limited in the present invention, and a method well known to those skilled in the art may be selected.
In the present invention, the cannabidiol-3-sulfonate may further increase the water solubility of cannabidiol-3-sulfonic acid.
In the present invention, the cannabidiol-3-sulfonic acid may be used to prepare cannabidiol-3-sulfonamide, and the method for preparing cannabidiol-3-sulfonamide from cannabidiol-3-sulfonic acid is not particularly limited, and may be a method known to those skilled in the art.
The invention provides a cannabidiol derivative prepared by the application of the technical scheme, which comprises cannabidiol-3-sulfonate and cannabidiol-3-sulfonamide.
In the present invention, the cannabidiol-3-sulfonate is preferably cannabidiol-3-sodium sulfonate, and has a structural formula of:
in the present invention, the cannabidiol-3-sulfonamide has the structural formula:
the technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The cannabidiol and the concentrated sulfuric acid are reacted according to the molar ratio of 1: 15.
Weighing 50g of concentrated sulfuric acid, adding into a three-neck flask, naturally cooling to 0 deg.C in ice water bath, adding 10.68g of cannabidiol, controlling the temperature to be lower than 20 deg.C, finishing the addition, then controlling the temperature to be 20 ℃, carrying out sulfonation reaction for 4 hours, stopping the reaction, pouring the obtained reaction liquid into an ice water bath, performing ethyl acetate extraction, concentrating the organic phase obtained by extraction at 50 ℃ under reduced pressure, loading the organic phase on a 200-300-mesh silica gel column, eluting 2 column volumes by using an eluent 1 (petroleum ether: ethyl acetate: methanol: 8:1:1), eluting 3 column volumes by using an eluent 2 (petroleum ether: ethyl acetate: methanol: 4:1:2), collecting the eluent 2, drying under reduced pressure, adding a proper amount of methanol at room temperature until all solids are dissolved, standing at room temperature, naturally volatilizing until crystals appear, and standing at 5-10 ℃ for 2-5 h to obtain a colorless needle-like crystalline compound (9.46 g).
The molecular weight of the compound is 394.53 by high resolution mass spectrometry, and the compound is confirmed to be cannabidiol-3-sulfonic acid by combined hydrogen spectrum (see figure 1). The structural formula is as follows:
example 2
The reaction is carried out according to the molar ratio of cannabidiol to concentrated sulfuric acid of 1: 30.
Weighing 50g of concentrated sulfuric acid, adding the concentrated sulfuric acid into a three-neck flask, naturally cooling to 0 ℃ in an ice water bath, adding 5.34g of cannabidiol, controlling the temperature to be lower than 15 ℃, finishing the addition, controlling the temperature to be 25 ℃, carrying out sulfonation reaction for 2 hours, stopping the reaction, pouring the obtained reaction liquid into the ice water bath, extracting by using ethyl acetate, drying an organic phase obtained by extraction under reduced pressure at 50 ℃, dissolving the organic phase into a 10% ethanol solution, loading the organic phase into an AB-8 type macroporous adsorption resin column, washing 5 column volumes by using 10% ethanol, washing 3 column volumes by using 50% ethanol, and finally washing the column by using 95% ethanol with 3 column volumes; collecting 50% ethanol elution part, drying under reduced pressure, adding appropriate amount of anhydrous ethanol until solid is completely dissolved, standing at room temperature, naturally volatilizing solvent until crystals appear, and standing at 5-10 deg.C for 2-5 hr to obtain colorless needle-like crystals, i.e. cannabidiol-3-sulfonic acid (4.37 g).
Example 3
The reaction is carried out according to the molar ratio of cannabidiol to concentrated sulfuric acid of 1: 20.
Weighing 50g of concentrated sulfuric acid, adding the concentrated sulfuric acid into a three-neck flask, naturally cooling to 0 ℃ in an ice water bath, adding 8g of cannabidiol, controlling the temperature to be lower than 25 ℃, completing the feeding, controlling the temperature to 35 ℃ to perform sulfonation reaction for 2 hours, stopping the reaction, pouring the obtained reaction liquid into a saturated NaCl solution with the volume of 20 times, standing, performing suction filtration after complete precipitation, washing the obtained reaction liquid to be nearly neutral by using the saturated NaCl solution, dissolving the obtained filter cake by using 5 times of water by weight at 80 ℃, adjusting the pH to be nearly neutral by using a 10% NaOH solution, filtering while hot, and performing cold storage at 5-10 ℃ to obtain colorless crystals, namely cannabidiol-3-sodium sulfonate (5.87 g).
The result of high-resolution mass spectrometry shows that the molecular weight of the product is 416.51, and the prepared sample is cannabidiol-3-sodium sulfonate by combining the analysis of the preparation process. The structural formula is as follows:
dissolving 1g of sodium cannabidiol-3-sulfonate in 10mL of 0.25mol.L-1In hydrochloric acid solution, extracting with equal volume of ethyl acetate, naturally volatilizing the solvent from the obtained organic phase, and analyzing by high resolution mass spectrometry to show that the molecular weight of the compound is 394.18. According to the preparation process, the prepared sample is cannabidiol-3-sulfonic acid, namely, cannabidiol-3-sodium sulfonate can be converted into cannabidiol-3-sulfonic acid.
Example 4
The addition of sulfonic acid group adds a new action site for cannabidiol, so that the structural modification of cannabidiol can be possible without great change of the basic structure parent nucleus, and the synthesis of cannabidiol-3-sulfonamide is used as an example in the embodiment.
The synthetic route of the cannabidiol-3-sulfonamide is as follows:
the specific synthetic process is as follows:
1) preparation of cannabidiol-3-sulfonyl chloride
Weighing 5g of cannabidiol-3-sulfonic acid (prepared in example 1), adding the weighed 5g of cannabidiol-3-sulfonic acid into 50g of phosphorus oxychloride, and carrying out reflux reaction for 15 hours; after the reaction is finished, pouring the obtained reaction liquid into 1L of ice/water mixed liquid, and extracting for three times by adopting dichloromethane, wherein the consumption of the dioxymethane is 500mL each time; and combining the obtained organic extraction phases, washing with brine, adding a proper amount of magnesium sulfate, drying, filtering, concentrating under reduced pressure to 50mL, adding n-hexane with the same volume, stirring for 30min, filtering, and washing the obtained filter cake with 100mL of dichloromethane/n-hexane (1:1, v/v) to obtain the cannabidiol-3-sulfonyl chloride (3.9 g).
2) Preparation of cannabidiol-3-sulfonamides
Under the condition of ice bath, slowly adding the 3.9g of cannabidiol-3-sulfonyl chloride into 20mL of concentrated ammonia water (stirring while adding), stopping ice bath, continuously stirring for reaction for 10min, then adding 15mL of water, slowly heating to 30 ℃, stirring for 30min to remove redundant ammonia, and at the moment, the reaction mixed liquid is gray paste; the reaction mixture was cooled in an ice bath, filtered, washed with a small amount of ice water, dried, dissolved in methanol and crystallized to obtain the desired product (2.7 g).
After high-resolution mass spectrometry, the molecular weight of the obtained target product is 393.54, and the structure of the target product is cannabidiol-3-sulfonamide through analysis of a hydrogen spectrogram (shown in figure 2), and the structural formula is as follows:
from example 4, it can be seen that the sulfonic acid group of the cannabidiol-3-sulfonic acid provided by the invention can also be used as a new action site to be combined with a specific group, so that the structural modification of the cannabidiol can be possible without great change of a basic structure mother nucleus.
Test example
1. And (3) measuring the solubility:
1) instruments and reagents: thermo Fisher UltiMate3000 high performance liquid chromatograph (Thermo corporation, usa); chromatography column (Phenomenex Gemini C18, 5 μ, 250 × 4.6 mm); electronic balance (mettler-toledo instruments (shanghai) ltd); cannabidiol (commercially available), cannabidiol-3-sulfonic acid (prepared in example 1) and cannabidiol-3-sulfonic acid sodium salt (prepared in example 3). Chromatographic acetonitrile (Merck, Germany, GmbH); the water was Milli-Q ultrapure water, and the remaining reagents were analytical grade.
2) Solution preparation
And (3) precisely adding 6mL of ultrapure water into three clean 10mL penicillin bottles, and precisely weighing. Respectively adding cannabidiol, cannabidiol-3-sulfonic acid and cannabidiol-3-sodium sulfonate at room temperature until the sample is not completely dissolved after ultrasonic treatment for 10min, and respectively obtaining saturated solutions of three compounds; standing at room temperature overnight, and collecting supernatant as test solution (the supernatant of cannabidiol-3-sulfonic acid and cannabidiol-3-sodium sulfonate is diluted by appropriate times according to detection conditions).
In addition, a proper amount of cannabidiol, cannabidiol-3-sulfonic acid and cannabidiol-3-sodium sulfonate is prepared into 0.2 mg/mL by 10% acetonitrile-0.5% acetic acid solution-1The solution of (4) as a control solution.
2) Sample detection
The measurement was carried out by high performance liquid chromatography (appendix V D of second part of the Chinese pharmacopoeia).
Octadecylsilane chemically bonded silica is used as a filler for chromatographic conditions and system applicability; taking 10% acetonitrile-0.5% acetic acid → 75% acetonitrile-0.5% acetic acid as mobile phase; the detection wavelength is 225 nm; the number of theoretical plates is not less than 4000 in terms of cannabidiol, cannabidiol-3-sulfonic acid and cannabidiol-3-sodium sulfonate.
The determination method comprises the following steps: precisely measuring 20 mu L of test solution, injecting into a liquid chromatograph, and recording chromatogram; the control solution was also used for measurement in the same manner. The concentrations of the three compounds in the test solution were calculated by peak area according to the external standard method, and the specific results are shown in table 1.
TABLE 1 solubility of cannabidiol, cannabidiol-3-sulfonic acid and cannabidiol-3-sodium sulfonate in water (Room temperature)
As can be seen from Table 1, cannabidiol is slightly soluble in water at room temperature, but its solubility increases to 56.21mg.mL after introduction of sulfonic acid groups-1And the solubility after salification is up to 485.77mg-1Can meet the requirement of general injection drugs on solubility.
The embodiments show that, compared with cannabidiol, the cannabidiol-3-sulfonic acid provided by the invention has obviously enhanced water solubility, and the cannabidiol-3-sulfonic acid can also undergo a salt forming reaction with an inorganic base or an organic base, so that the water solubility of the cannabidiol compound is further increased, and the pharmaceutical property of the drug based on the CBD structure parent nucleus and physiological activity is increased; in addition, on the premise of ensuring that the basic structure mother nucleus of the cannabidiol is not changed greatly, the sulfonic group newly introduced into the cannabidiol-3-sulfonic acid provided by the invention can be used as a new action site to react with a specific group, so that the research and application range of the cannabidiol-3-sulfonic acid can be further widened.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.