CN106810426A - A kind of synthetic method of cannabidiol - Google Patents
A kind of synthetic method of cannabidiol Download PDFInfo
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- CN106810426A CN106810426A CN201611245047.XA CN201611245047A CN106810426A CN 106810426 A CN106810426 A CN 106810426A CN 201611245047 A CN201611245047 A CN 201611245047A CN 106810426 A CN106810426 A CN 106810426A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/50—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions decreasing the number of carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/84—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by crystallisation
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- C07B2200/07—Optical isomers
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Abstract
The invention provides one kind with 2, the pentyl methyl benzoate of 4 dihydroxy 6 is raw material, with N under potassium hydroxide catalysed, N dialkyl group hydramine carries out ester exchange, then with (1S, 4R) there is coupling reaction in 1 methyl 4 (1 methyl ethylene) alcohol of 2 cyclohexene 1 under Lewis acid catalysis, the key intermediate product of high-purity is obtained after soda acid extraction and recrystallization, crude product cannabidiol is obtained by hydrolysis decarboxylation again, crude product once recrystallizes the cannabidiol that can be obtained by meeting bulk drug quality requirement.Raw material and reagent in the inventive method are cheap, be commercially easy to get, and gross production rate reaches as high as 35 ~ 40% during last obtained qualified purity bulk drug, and technique is significantly improved, and it has good prospects for commercial application.
Description
Technical field
The present invention relates to a kind of synthetic method of cannabidiol, belong to technical field of organic synthesis.
Background technology
Cannabidiol alias is left-handed-trans-cannabidiol, entitled (-)-Cannabidiol of English, is have very much market price
The bulk drug of value, the structural formula of compound is：
Current cannabidiol is applied primarily to protection nerve, anti-spasm, the effect such as anti-inflammatory and antianxiety.Britain in 2015
GW biopharmaceutical companys announce：Its pure cannabidiol is updated for the clinical trial data of intractable epilepsy in childhood disease, 2014
This medicine has obtained the accreditation of the rare sick medicine of U.S. FDA and the examination ＆ approval of fast passage, and for treating baby's severe myoclonic epilepsy, this makes
The market prospects for obtaining this medicine become more extensive.Inexpensively, it is efficient and easy to operate, it is suitable for the synthesis work of industrialized production
Skill, will also have very big impetus for the application of cannabidiol.
Using olivetol as initiation material, with Catalyzed by p-Toluenesulfonic Acid, one-step method obtains target and produces US20090036523A1
Thing, it is specific as follows to be：
But the reaction system is complicated, there are more isomers and dimer, post processing trouble, it is necessary to column chromatography purifying and yield
It is relatively low, only 24%, it is unsuitable for amplifying production.
WO2006053766A1 then carries out the synthesis of target product using zinc chloride catalysis.The document reports one kind only
Post purifying obtains the technique of product, but product purity only has 97.1%, and yield only has 22%.We are repeated to the document
Experiment find course of reaction it is maximum single it is miscellaneous be dimer, reach more than 20%, the impurity needs crystallized above can just be down to for 3 times
(bulk drug index request is reached within 0.1%).Total recovery only has 13% when finally obtaining acceptable material medicine, process costs compared with
It is high.
US20100298579A1, for initiation material, uses boron trifluoride second with 2,4- dihydroxy -6- pentyls methyl benzoate
Ether is catalyzed, and prepares the methyl ester intermediate (I) of coupling, and the reaction purity is more slightly higher than one-step method, and isomers and dimer are also obvious
It is fewer than one-step method.But methyl ester intermediate still only has about 75% purity, the in addition change by purity after soda acid treatment after coupling
The fusing point of compound may be relatively low, it is impossible to crystallizes that (intermediate compound I has no that fusing point is reported, even if will cross post obtains purity up in 98%
Mesosome I is crystallized, and finally cannot also analyse into solid).Methyl ester intermediate I cannot carry out recrystallization purifying by conventional method,
So as to be unable to reach as the chemical purity and single miscellaneous index request of the key intermediate of bulk drug.
In addition to both the above chemical synthesis process, the also biological method extracted of part document report obtains hemp
Diphenol, but such method and step is relatively complicated, and industrialized production limitation is too big.
The content of the invention
It is an object of the invention to solve above-mentioned technical problem, there is provided a kind of synthetic method of cannabidiol.
The purpose of the present invention is achieved through the following technical solutions：
A kind of synthetic method of cannabidiol, its reaction equation is as follows,
Comprise the following steps：
S1, with 2,4- dihydroxy -6- amyl groups methyl benzoate for raw material, with N, N- dialkyl group alcohol under potassium hydroxide effect
Intermediate one obtained and ester exchange reaction in amine there is；N=1~8 in the intermediate one, the R is methyl, ethyl, propyl group and fourth
Any one in base；
S2, by intermediate obtained in S1 one and (1S, 4R) -1- methyl -4- (1- methyl ethylenes) -2- cyclohexene -1- alcohol
Carry out coupling reaction and prepare intermediate two；N=1~8 in intermediate two, the R is in methyl, ethyl, propyl group and butyl
Any one；
S3, by the pyrohydrolysis decarboxylation under NaOH effect of obtained intermediate two, is finally obtained cannabidiol.
Preferably, the S1 comprises the following steps：
S11, with 2,4- dihydroxy -6- amyl groups methyl benzoate be raw material and N, N- dialkyl group hydramine, potassium hydroxide make
Under, protected by nitrogen and reacted；
S12, by adding acid solution, regulation pH value of solution is extracted first to acidity；
S13, pH value of solution to alkalescence is adjusted by adding alkali, is extracted again；
S14, washing, drying, carry out being concentrated under reduced pressure to give intermediate one.
Preferably, it is 2-3 that pH value of solution is adjusted in the S12.
Preferably, it is 10 that pH value of solution is adjusted in the S12.
Preferably, pH is adjusted by adding alkali solid in the S13.
Preferably, by adding alkali solid for water phase sodium carbonate solid in the S13.Certainly, alkali base solid is adjusted
Or solution can be so that it is the sodium carbonate to avoid alkali tune water consumption too big, potassium carbonate, cesium carbonate, NaOH, hydrogen to add solid
Potassium oxide these conventional alkali can.
Preferably, the S2 comprises the following steps：
S21, intermediate one is with (1S, 4R) -1- methyl -4- (1- methyl ethylenes) -2- cyclohexene -1- alcohol in anhydrous chlorination
Zinc catalysis is lower to there is condensation reaction；
S22, reaction adds acid after terminating, and the method extracted by soda acid is purified and purity is obtained is at least 90% and can tie again
The crude product of brilliant intermediate two；
S23, the crude product of intermediate two passes through the bulk drug key intermediate two of solvent recrystallization synthesis of high purity.
Preferably, acid is hydrochloric acid, sulfuric acid, acetic acid, any one in oxalic acid and citric acid in the S22.
Preferably, the solvent in shown S23 is petroleum ether, pentane, any one in n-hexane and normal heptane.
Preferably, the purity of the cannabidiol obtained in approach described above is 99.88% -99.98%.
Beneficial effects of the present invention：Raw material and reagent in the inventive method are cheap, be commercially easy to get, and are handed over by ester
Change, be coupled, decarboxylation three-step reaction can obtain high-quality cannabidiol.Although the technique step increases to 3 steps, in each step
Mesosome can be by recrystallization purifying, and list is miscellaneous to can reach bulk drug intermediate index, last obtained qualified purity raw material
Gross production rate reaches as high as 35~40% during medicine, and technique is significantly improved, and it has good prospects for commercial application.
Specific embodiment
The method of the present invention is illustrated below by specific embodiment, so that technical solution of the present invention is easier to reason
Solution, grasp, but the invention is not limited in this.Experimental technique described in following embodiments, unless otherwise specified, is conventional side
Method；The reagent and material, unless otherwise specified, commercially obtain.
Employed in the present invention in embodiment when pH is adjusted, what is used in the application is sodium carbonate, but is not limited to
This, potassium carbonate, cesium carbonate, NaOH, potassium hydroxide these conventional alkali can.Other modulability auxiliary reagents, also
With being replaced using other routines.
Embodiment one
The preparation of intermediate one：
First, by 2, the 4- dihydroxy -6- pentyls methyl benzoate and the N of 89g of 119g, N- dimethylethanolamines are added
In 250mL there-necked flasks, stirring is lower to add the potassium hydroxide of 30.8g, nitrogen protection, is warming up to 130 DEG C of stirring reactions 4 hours.
Reaction solution is cooled to less than 30 DEG C, pH to 2~3 is adjusted with 1N aqueous hydrochloric acid solutions, add normal heptane (250mL × 2) extraction, water phase
Sodium carbonate solid adjusts pH to 10, adds normal heptane (250mL × 2) extraction, washes (150mL) once, anhydrous sodium sulfate drying,
It is concentrated under reduced pressure into the dry normal heptane for adding 4v/m afterwards to recrystallize, 103g, yield 70%, HPLC purity is obtained after drying
99.84%.
The preparation of intermediate two：
By in the dichloromethane addition 2000mL there-necked flasks of the above-mentioned ester exchange sterlings of 100g and 800mL, stirring is lower to be added
The zinc chloride of 50.8g, the water of 8g, 25 DEG C are stirred 0.5 hour, and (1S, 4R) -1- methyl -4- (1- ethylene methacrylics of 46.4g are added dropwise
Base) -2- cyclohexene -1- alcohol, system not heat release substantially, insulated and stirred 24h after completion of dropping.By reaction solution be cooled to 10 DEG C with
Under, with 1N aqueous hydrochloric acid solutions adjust pH to 2~3, add normal heptane (500mL × 2) extraction, water phase sodium carbonate solid adjust pH to
10, normal heptane (500mL × 2) extraction is added, once, anhydrous sodium sulfate drying is concentrated under reduced pressure into slightly dry for washing (300mL)
Product.Crude product adds 40 DEG C of heating for dissolving of normal heptane of 4v/m, is cooled to -5~5 DEG C and is incubated crystallization 16 hours, suction filtration, after drying
Obtain the white solid of 60.2g, yield 46%, HPLC purity 99.98%.
The synthesis of cannabidiol：
By in the above-mentioned coupling products of 50g and 250mL methyl alcohol addition 1000mL there-necked flasks, under nitrogen protection, 5v/m is added
3N sodium hydrate aqueous solutions, be warming up to 95 DEG C of insulation reactions 8 hours, be cooled within 25 DEG C, add normal heptane (200mL*2)
Extraction, merges organic phase and is washed once with 100mL saturated sodium-chlorides, is concentrated under reduced pressure into dry, the normal heptane recrystallization of addition 4v/m, -5
~5 DEG C are incubated crystallization 16 hours, and suction filtration obtains the white solid of 33.7g, yield 92%, HPLC purity after drying
99.93%.
Embodiment two
The preparation of intermediate one：
2,4- dihydroxy -6- pentyls the methyl benzoate and the N of 234g of 119g, N- dimethyl butyrates hydramine are added
In 500mL there-necked flasks, stirring is lower to add the potassium hydroxide of 33.6g, nitrogen protection, is warming up to 130 DEG C of stirring reactions 4 hours.
Reaction solution is cooled to less than 30 DEG C, pH to 2~3 is adjusted with 1N aqueous hydrochloric acid solutions, add normal heptane (250mL × 2) extraction, water phase
Sodium carbonate solid adjusts pH to 10, adds normal heptane (250mL × 2) extraction, washes (150mL) once, anhydrous sodium sulfate drying,
It is concentrated under reduced pressure into the dry normal heptane for adding 4v/m afterwards to recrystallize, 134.1g, yield 83%, HPLC purity is obtained after drying
99.97%.
The preparation of intermediate two：
By in the dichloromethane addition 2000mL there-necked flasks of the above-mentioned ester exchange sterlings of 100g and 800mL, stirring is lower to be added
The zinc chloride of 46.4g, the water of 7.3g, 25 DEG C are stirred 0.5 hour, and (1S, 4R) -1- methyl -4- (1- methyl second of 42.4g is added dropwise
Alkenyl) -2- cyclohexene -1- alcohol, system not heat release substantially, insulated and stirred 24h after completion of dropping.By reaction solution be cooled to 10 DEG C with
Under, with 1N aqueous sulfuric acids adjust pH to 2~3, add normal heptane (500mL × 2) extraction, water phase sodium carbonate solid adjust pH to
10, normal heptane (500mL × 2) extraction is added, once, anhydrous sodium sulfate drying is concentrated under reduced pressure into slightly dry for washing (300mL)
Product.Crude product adds 40 DEG C of heating for dissolving of petroleum ether of 4v/m, is cooled to -5~5 DEG C and is incubated crystallization 16 hours, suction filtration, after drying
Obtain the white solid of 53.5g, yield 42%, HPLC purity 99.98%.
The synthesis of cannabidiol：
By in the above-mentioned coupling products of 50g and 250mL methyl alcohol addition 1000mL there-necked flasks, under nitrogen protection, 5v/m is added
3N sodium hydrate aqueous solutions, be warming up to 95 DEG C of insulation reactions 8 hours, be cooled within 25 DEG C, add normal heptane (200mL*2)
Extraction, merges organic phase and is washed once with 100mL saturated sodium-chlorides, is concentrated under reduced pressure into dry, the normal heptane recrystallization of addition 4v/m, -5
~5 DEG C are incubated crystallization 16 hours, and suction filtration obtains the white solid of 31.3g, yield 91%, HPLC purity after drying
99.95%.
Embodiment three：
The preparation of intermediate one：
2,4- dihydroxy -6- pentyls the methyl benzoate and the N of 145g of 119g, N- Exxal8s amine are added
In 250mL there-necked flasks, stirring is lower to add the potassium hydroxide of 30.8g, nitrogen protection, is warming up to 130 DEG C of stirring reactions 4 hours.
Reaction solution is cooled to less than 30 DEG C, pH to 2~3 is adjusted with 1N aqueous hydrochloric acid solutions, add normal heptane (250mL × 2) extraction, water phase
Sodium carbonate solid adjusts pH to 10, adds normal heptane (250mL × 2) extraction, washes (150mL) once, anhydrous sodium sulfate drying,
It is concentrated under reduced pressure into the dry normal heptane for adding 4v/m afterwards to recrystallize, 142.2g, yield 81%, HPLC purity is obtained after drying
99.75%.
The preparation of intermediate two：
By in the dichloromethane addition 2000mL there-necked flasks of the above-mentioned ester exchange sterlings of 100g and 800mL, stirring is lower to be added
The zinc chloride of 43.8g, the water of 6.9g, 25 DEG C are stirred 0.5 hour, and (1S, 4R) -1- methyl -4- (1- ethylene methacrylics of 40g are added dropwise
Base) -2- cyclohexene -1- alcohol, system not heat release substantially, insulated and stirred 24h after completion of dropping.By reaction solution be cooled to 10 DEG C with
Under, with 1N aqueous sulfuric acids adjust pH to 2~3, add normal heptane (500mL × 2) extraction, water phase sodium carbonate solid adjust pH to
10, normal heptane (500mL × 2) extraction is added, once, anhydrous sodium sulfate drying is concentrated under reduced pressure into slightly dry for washing (300mL)
Product.Crude product adds 40 DEG C of heating for dissolving of n-hexane of 4v/m, is cooled to -5~5 DEG C and is incubated crystallization 16 hours, suction filtration, after drying
Obtain the white solid of 58.5g, yield 47%, HPLC purity 99.91%.
The synthesis of cannabidiol：
By in the above-mentioned coupling products of 50g and 250mL methyl alcohol addition 1000mL there-necked flasks, under nitrogen protection, 5v/m is added
3N sodium hydrate aqueous solutions, be warming up to 90 DEG C of insulation reactions 4 hours, be cooled within 25 DEG C, add normal heptane (200mL*2)
Extraction, merges organic phase and is washed once with 100mL saturated sodium-chlorides, is concentrated under reduced pressure into dry, the normal heptane recrystallization of addition 4v/m, -5
~5 DEG C are incubated crystallization 16 hours, and suction filtration obtains the white solid of 30.4g, yield 94%, HPLC purity after drying
99.88%.
Example IV：
The preparation of intermediate one：
2,4- dihydroxy -6- pentyls the methyl benzoate and the N of 145.3g of 119g, N- dipropylethanolamines are added
In 250mL there-necked flasks, stirring is lower to add the potassium hydroxide of 30.8g, nitrogen protection, is warming up to 130 DEG C of stirring reactions 4 hours.
Reaction solution is cooled to less than 30 DEG C, pH to 2~3 is adjusted with 1N aqueous hydrochloric acid solutions, add normal heptane (250mL × 2) extraction, water phase
Sodium carbonate solid adjusts pH to 10, adds normal heptane (250mL × 2) extraction, washes (150mL) once, anhydrous sodium sulfate drying,
It is concentrated under reduced pressure into the dry normal heptane for adding 4v/m afterwards to recrystallize, 127.8g, yield 81%, HPLC purity is obtained after drying
99.63%.
The preparation of intermediate two：
By in the dichloromethane addition 2000mL there-necked flasks of the above-mentioned ester exchange sterlings of 100g and 800mL, stirring is lower to be added
The zinc chloride of 43.8g, the water of 6.9g, 25 DEG C are stirred 0.5 hour, and (1S, 4R) -1- methyl -4- (1- ethylene methacrylics of 40g are added dropwise
Base) -2- cyclohexene -1- alcohol, system not heat release substantially, insulated and stirred 24h after completion of dropping.By reaction solution be cooled to 10 DEG C with
Under, with 1N aqueous sulfuric acids adjust pH to 2~3, add normal heptane (500mL × 2) extraction, water phase sodium carbonate solid adjust pH to
10, normal heptane (500mL × 2) extraction is added, once, anhydrous sodium sulfate drying is concentrated under reduced pressure into slightly dry for washing (300mL)
Product.Crude product adds 40 DEG C of heating for dissolving of normal heptane of 4v/m, is cooled to -5~5 DEG C and is incubated crystallization 16 hours, suction filtration, after drying
Obtain the white solid of 51g, yield 41%, HPLC purity 99.86%.
The synthesis of cannabidiol：
By in the above-mentioned coupling products of 50g and 250mL methyl alcohol addition 1000mL there-necked flasks, under nitrogen protection, 5v/m is added
3N sodium hydrate aqueous solutions, be warming up to 95 DEG C of insulation reactions 8 hours, be cooled within 25 DEG C, add normal heptane (200mL*2)
Extraction, merges organic phase and is washed once with 100mL saturated sodium-chlorides, is concentrated under reduced pressure into dry, the normal heptane recrystallization of addition 4v/m, -5
~5 DEG C are incubated crystallization 16 hours, and suction filtration obtains the white solid of 28.5g, yield 88%, HPLC purity after drying
99.97%.
The present invention still has various specific embodiments.All use equivalents or equivalent transformation and all skills for being formed
Art scheme, all falls within the scope of protection of present invention.
Claims (10)
1. a kind of synthetic method of cannabidiol, it is characterised in that：Its reaction equation is as follows,
Comprise the following steps：
S1, with 2,4- dihydroxy -6- amyl groups methyl benzoate for raw material, with N under potassium hydroxide effect, N- dialkyl group hydramine hair
Raw ester exchange reaction obtains intermediate one；N=1~8 in the intermediate one, the R is in methyl, ethyl, propyl group and butyl
Any one；
S2, intermediate obtained in S1 one and (1S, 4R) -1- methyl -4- (1- methyl ethylenes) -2- cyclohexene -1- alcohol are carried out
Coupling reaction prepares intermediate two；N=1~8 in intermediate two, the R is appointing in methyl, ethyl, propyl group and butyl
Meaning is a kind of；
S3, by the pyrohydrolysis decarboxylation under NaOH effect of obtained intermediate two, is finally obtained cannabidiol.
2. the synthetic method of a kind of cannabidiol according to claim 1, it is characterised in that：The S1 includes following step
Suddenly：
S11, with 2,4- dihydroxy -6- amyl groups methyl benzoate be raw material and N, N- dialkyl group hydramine, potassium hydroxide effect under,
Protected by nitrogen and reacted；
S12, by adding acid solution, regulation pH value of solution is extracted first to acidity；
S13, pH value of solution to alkalescence is adjusted by adding alkali, is extracted again；
S14, washing, drying, carry out being concentrated under reduced pressure to give intermediate one.
3. the synthetic method of a kind of cannabidiol according to claim 2, it is characterised in that：Solution is adjusted in the S12
PH is 2-3.
4. the synthetic method of a kind of cannabidiol according to claim 2, it is characterised in that：Solution is adjusted in the S12
PH is 10.
5. the synthetic method of a kind of cannabidiol according to claim 2, it is characterised in that：By addition in the S13
Alkali solid adjusts pH.
6. the synthetic method of a kind of cannabidiol according to claim 5, it is characterised in that：By addition in the S13
Alkali solid is water phase sodium carbonate solid.
7. the synthetic method of a kind of cannabidiol according to claim 1, it is characterised in that：The S2 includes following step
Suddenly：
S21, intermediate one is urged with (1S, 4R) -1- methyl -4- (1- methyl ethylenes) -2- cyclohexene -1- alcohol in anhydrous zinc chloride
Change lower generation condensation reaction；
S22, reaction adds acid after terminating, and the method that is extracted by soda acid is purified purity is obtained to be at least 90% and recrystallized
The crude product of intermediate two；
S23, the crude product of intermediate two passes through the bulk drug key intermediate two of solvent recrystallization synthesis of high purity.
8. the synthetic method of a kind of cannabidiol according to claim 7, it is characterised in that：Acid is hydrochloric acid in the S22,
Any one in sulfuric acid, acetic acid, oxalic acid and citric acid.
9. the synthetic method of a kind of cannabidiol according to claim 7, it is characterised in that：Solvent in shown S23 is
Any one in petroleum ether, pentane, n-hexane and normal heptane.
10. cannabidiol, its feature according to obtained in the synthetic method of any described a kind of cannabidiol in claim 1-9
It is：The purity of the cannabidiol is 99.88% -99.98%.
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020524679A (en) * | 2017-06-20 | 2020-08-20 | イッサム リサーチ デベロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム エルティーディー． | Cannabidiol ester composition and use thereof |
| CN111943813A (en) * | 2019-05-17 | 2020-11-17 | 上海特化医药科技有限公司 | Preparation method of cannabidiol compound |
| CN112047815A (en) * | 2020-10-10 | 2020-12-08 | 成都海博为药业有限公司 | Preparation method of cannabidiol compound |
| CN112062697A (en) * | 2019-05-22 | 2020-12-11 | 上海特化医药科技有限公司 | M-benzene polyphenol derivative and preparation method thereof |
| US11040932B2 (en) | 2018-10-10 | 2021-06-22 | Treehouse Biotech, Inc. | Synthesis of cannabigerol |
| US11084770B2 (en) | 2016-12-07 | 2021-08-10 | Treehouse Biotech, Inc. | Cannabis extracts |
| CN113603568A (en) * | 2021-07-19 | 2021-11-05 | 厦门朝阳生物工程有限公司 | Preparation method of cannabidiol |
| US11202771B2 (en) | 2018-01-31 | 2021-12-21 | Treehouse Biotech, Inc. | Hemp powder |
| CN114634403A (en) * | 2022-03-10 | 2022-06-17 | 南京康立瑞生物科技有限公司 | Preparation method of 3, 6-dimethyl-1, 2-benzenediol |
| CN115504864A (en) * | 2021-06-07 | 2022-12-23 | 南通新世元生物科技有限公司 | Method for obtaining high-purity cannabidiol from industrial cannabis sativa |
| CN115583933A (en) * | 2022-10-31 | 2023-01-10 | 暨明医药科技（苏州）有限公司 | Preparation method of high-purity tetrahydrocannabinoid homolog |
| CN115677456A (en) * | 2022-11-11 | 2023-02-03 | 暨明医药科技（苏州）有限公司 | Preparation method of cannabidiol |
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