CN114602438A - Preparation method of special chromatographic medium for separating hypocannabidiol - Google Patents
Preparation method of special chromatographic medium for separating hypocannabidiol Download PDFInfo
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- CN114602438A CN114602438A CN202011419602.2A CN202011419602A CN114602438A CN 114602438 A CN114602438 A CN 114602438A CN 202011419602 A CN202011419602 A CN 202011419602A CN 114602438 A CN114602438 A CN 114602438A
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- cannabidiol
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- chromatographic medium
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- hypocannabidiol
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- 239000012501 chromatography medium Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 claims abstract description 45
- 229950011318 cannabidiol Drugs 0.000 claims abstract description 45
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 claims abstract description 44
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 claims abstract description 44
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 claims abstract description 44
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- OBFQBDOLCADBTP-UHFFFAOYSA-N aminosilicon Chemical compound [Si]N OBFQBDOLCADBTP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 21
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- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
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- 229960000583 acetic acid Drugs 0.000 claims description 3
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- 239000002245 particle Substances 0.000 claims description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 7
- 239000002609 medium Substances 0.000 abstract description 6
- 238000001179 sorption measurement Methods 0.000 abstract description 6
- 238000013375 chromatographic separation Methods 0.000 abstract description 3
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- 238000001914 filtration Methods 0.000 abstract description 2
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- 239000000377 silicon dioxide Substances 0.000 abstract description 2
- 239000000945 filler Substances 0.000 abstract 1
- REOZWEGFPHTFEI-JKSUJKDBSA-N Cannabidivarin Chemical compound OC1=CC(CCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 REOZWEGFPHTFEI-JKSUJKDBSA-N 0.000 description 8
- 241000218236 Cannabis Species 0.000 description 8
- REOZWEGFPHTFEI-UHFFFAOYSA-N cannabidivarine Natural products OC1=CC(CCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 REOZWEGFPHTFEI-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 244000025254 Cannabis sativa Species 0.000 description 5
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 5
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 5
- 235000009120 camo Nutrition 0.000 description 5
- 235000005607 chanvre indien Nutrition 0.000 description 5
- 239000011487 hemp Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 4
- QXACEHWTBCFNSA-SFQUDFHCSA-N cannabigerol Chemical compound CCCCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-SFQUDFHCSA-N 0.000 description 4
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 4
- 229960004242 dronabinol Drugs 0.000 description 4
- QXACEHWTBCFNSA-UHFFFAOYSA-N cannabigerol Natural products CCCCCC1=CC(O)=C(CC=C(C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-UHFFFAOYSA-N 0.000 description 3
- 238000010262 high-speed countercurrent chromatography Methods 0.000 description 3
- VBGLYOIFKLUMQG-UHFFFAOYSA-N Cannabinol Chemical class C1=C(C)C=C2C3=C(O)C=C(CCCCC)C=C3OC(C)(C)C2=C1 VBGLYOIFKLUMQG-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
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- 239000011259 mixed solution Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- -1 cannabichromel (CBC) Chemical compound 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
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- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
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- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
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- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
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- 239000001301 oxygen Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920006122 polyamide resin Polymers 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28016—Particle form
- B01J20/28021—Hollow particles, e.g. hollow spheres, microspheres or cenospheres
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
- B01D15/163—Pressure or speed conditioning
- B01D15/165—Flash chromatography
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/265—Adsorption chromatography
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28004—Sorbent size or size distribution, e.g. particle size
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- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
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- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
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- B01J20/3214—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
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- C—CHEMISTRY; METALLURGY
- 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
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Abstract
The invention relates to a preparation method of a special chromatographic medium for separating cannabidiol, which comprises the following preparation steps: (1) reacting elemental bromine, the cannabidiol bromide and a catalyst to obtain a brominated cannabidiol intermediate; (2) adding a certain amount of porous amino silicon spheres into an organic solvent, and fully stirring to completely wet the porous amino silicon spheres; (3) then adding the brominated hypocannabidiol intermediate and a catalyst into the solution for heating reaction. After the reaction is finished, filtering and drying are carried out, thus obtaining the special chromatographic separation medium. Bonding the hypocannabidiol to the silica spheres to form a surface modified silica gel chromatographic filler; the medium has high selective adsorption retention on the hypocannabinol, has the advantages of good selectivity and low cost, and is suitable for industrial purification of the hypocannabinol.
Description
Technical Field
The invention relates to the technical field of chromatographic media, in particular to a preparation method of a chromatographic medium special for separating hypocannabidiol.
Background
Cannabis is a plant of cannabinaceae and cannabis, commonly known as hemp, hemp seed and hemp, has a long planting history and important agricultural and medicinal values, and cannabis contains a toxic component Tetrahydrocannabinol (THC) which can cause people to be fantastic addict, is often used by people to extract drugs and has been prohibited for a long time.
Cannabis has now been generally recognized as having significant benefits for a variety of medical uses, for example cannabis is often used extensively by society to treat a variety of diseases, ailments and symptoms including nausea, pain, glaucoma, loss of appetite, mucosal inflammation, neurodegenerative diseases, epilepsy, diabetes, leprosy and the like, as well as the usual fever, cough, obesity, asthma, urinary tract infections, and Post Traumatic Stress Disorder (PTSD) and autoimmune diseases. Industrial cannabis contains a number of cannabinol compounds with medicinal value, among which Cannabidiol (CBD), Cannabidivarin (CBDV), Cannabinol (CBN), Cannabigerol (CBG), cannabichromel (CBC), Tetrahydrocannabinol (THC), Tetrahydrocannabivarinol (THCV), etc. are mainly used. In particular, the Cannabidiol (CBDV) has obvious curative effect on the aspects of epilepsy, dyskinesia and nerve function loss.
Because the economic value and the medicinal value of the cannabis are extremely high, the cannabidiol hypo (CBDV) has better performance on nervous system diseases, and how to obtain the cannabidiol with medical purity becomes a hot problem. The prior methods for purifying the cannabidiol hypo in the cannabis are few, and generally comprise the following steps:
the high-speed counter-current chromatography is characterized in that a special unidirectional hydrodynamic equilibrium is established in a spiral tube rotating at high speed by utilizing a two-phase solvent system, wherein one phase is used as a fixed phase, the other phase is used as a mobile phase, and substances are separated according to different distribution coefficients in the two phases, so that the loss, inactivation, denaturation and the like of a sample caused by non-adsorbability are avoided, and the high-speed counter-current chromatography is very suitable for separating natural active biological components. Patent CN 110590511 a provides a method for simultaneously separating cannabidiol and cannabigerol, which adopts high-speed counter-current chromatography to separate, respectively obtain a mixed solution of cannabidiol and a mobile phase, and a mixed solution of cannabigerol and a mobile phase, and remove the mobile phase, respectively obtain cannabidiol and cannabigerol.
The crystallization method is to obtain a solution containing the product to be crystallized by a series of means such as column chromatography, elution chromatography, and then to remove the organic solvent to obtain the crystallized product. Chinese patent publication No. CN 109574810 a discloses a method for simultaneously extracting CBD and CBDV, which comprises extracting hemp powder with organic solvent (ethanol), passing through macroporous resin adsorption column, and eluting with low-concentration and high-concentration ethanol respectively to obtain CBDV and CBD, wherein the purity of CBDV can reach 98%.
Chinese patent publication No. CN 110655453 a provides a method for extracting and separating hypocannabinol, which comprises extracting with ethanol water solution, extracting and enriching hypocannabinol with organic solvent, decolorizing with activated carbon, purifying and enriching with polyamide resin column, neutral alumina and bonded silica gel column, and crystallizing to obtain high-purity hypocannabinol. Chinese patent publication No. CN 110143854A discloses a method for simultaneously extracting CBD and CBDV, which comprises standing fresh hemp leaves in oxygen-enriched environment for a period of time, extracting with organic solvent solution, and crystallizing the extractive solution with gradient solution to obtain CBD and CBDV.
The existing process for producing the hypocannabidiol has many defects, such as low yield, complicated steps, incapability of large-scale preparation and the like. In order to solve the problems, the patent provides a preparation method of a special chromatographic medium for separating the cannabidiol, the chromatographic medium has special adsorption capacity on the cannabidiol, the bonded fixed phase enhances the separation of the cannabidiol from other phenols relative to the adsorption of the cannabidiol, and the preparation type chromatographic column is filled for purifying the cannabidiol, so that the operation is simple, the purity is high, and the method can be used for large-scale production.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of a special chromatographic medium for separating hypocannabidiol.
The purpose of the invention is realized by the following technical scheme:
a method for preparing a chromatographic medium special for separating hypocannabidiol,
reacting elemental bromine, hypocannabidiol and a catalyst to obtain a brominated hypocannabidiol intermediate;
the mass ratio of the elemental bromine to the cannabidiol is 9: 1-2: 1;
the catalyst is glacial acetic acid.
The mass of the catalyst is 0.1-5% of that of the hypocannabidiol;
secondly, adding the porous amino silicon balls into an organic solvent, and fully stirring to completely wet the porous amino silicon balls;
the particle size of the porous amino silicon ball is 10-500 microns;
the mass of the porous amino silicon ball is 10-50 times of that of the cannabidiol;
the organic solvent is one of xylene, carbon disulfide and dimethyl sulfoxide, and xylene is preferred;
thirdly, adding a brominated sub-cannabidiol intermediate and a catalyst into the solution for heating reaction;
the catalyst is one of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide, 1-hydroxybenzotriazole and N-hydroxysuccinimide, preferably 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide;
the mass of the catalyst is 0.1-5% of that of the cannabidiol.
The heating temperature is 70-85 ℃.
Compared with the prior art, the invention has the positive effects that:
the invention prepares a special chromatographic separation medium for purifying the hypocannabinol, and then combines column chromatography to purify the hypocannabinol, so as to obtain the high-purity hypocannabinol with the purity of more than 99 percent. The method has the advantages of simple process, easy operation and high purity, and can be used for industrial preparation.
Drawings
FIG. 1 is a prior art stationary phase bonding formula;
FIG. 2 is a chemical synthesis scheme of the present invention;
FIG. 3 is an HPLC chromatogram of crude hypocannabidiol of example 1;
FIG. 4 is an HPLC chromatogram of the purified hypocannabidiol of example 1.
Detailed Description
The following provides a specific implementation mode of the preparation method of the chromatographic medium special for separating the cannabidiol.
Example 1
The method comprises the following specific steps:
(1) weighing 15g of elemental bromine, 3g of cannabidiol and 0.1g of glacial acetic acid, and mixing for reaction;
(2) weighing 30g of porous amino silicon spheres with the particle size of 50 mu m, adding the porous amino silicon spheres into dimethylbenzene, and fully stirring to completely wet the porous amino silicon spheres;
(3) then adding the cannabidiol bromide intermediate and 0.1g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide into the solution, and reacting at 75 ℃.
After the reaction is finished, filtering and drying are carried out, and the special chromatographic separation medium is obtained and is filled into a column.
Column: 15 x 310mm, 50 microns,
wavelength: 210nm
Mobile phase: methanol-water
Flow rate: 10.6ml/min
10g of crude cannabidiol extracted by solvent method was analyzed by C18 reverse phase chromatography, as shown in FIG. 3. Separating and purifying cannabidiol with a packed preparative chromatographic column to obtain 1.2g of cannabidiol, and analyzing the purified cannabidiol with a C18 reverse phase chromatographic column, as shown in FIG. 4, with a purity as high as 99.80% and a peak value shown in Table 1.
TABLE 1
| Peak # | Retention time | Area of | Height | Percentage of |
| 1 | 10.687 | 4952076 | 285052 | 99.80 |
| 2 | 15.829 | 10352 | 1268 | 0.20 |
The surface modified silica gel chromatographic packing is formed by bonding the hypocannabidiol to the silica spheres. The medium provides pi-pi interaction by utilizing a benzene ring skeleton and a conjugated double bond structure of a sub-cannabidiol skeleton; providing hydrogen bonding interactions using phenolic hydroxyl groups; the amide functionality is utilized to provide selective adsorption of phenolic hydroxyl groups. The medium has high selective adsorption retention on the hypocannabinol, has the advantages of good selectivity and low cost, and is suitable for industrial purification of the hypocannabinol.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and decorations can be made without departing from the concept of the present invention, and these modifications and decorations should also be regarded as being within the protection scope of the present invention.
Claims (10)
1. A preparation method of a special chromatographic medium for separating cannabidiol is characterized by comprising the following specific steps:
reacting elemental bromine, hypocannabidiol and a catalyst to obtain a brominated hypocannabidiol intermediate;
secondly, adding the porous amino silicon balls into an organic solvent, and fully stirring to completely wet the porous amino silicon balls;
thirdly, adding a hypocannabidiol bromide intermediate and a catalyst into the solution for heating reaction; obtaining the chromatographic medium special for separating the cannabidiol.
2. The method for preparing a chromatographic medium specially used for separating cannabidiol as claimed in claim 1, wherein in the first step, the mass ratio of the simple substance bromine to the cannabidiol is 9: 1-2: 1.
3. The method as claimed in claim 1, wherein in step one, the catalyst is glacial acetic acid.
4. The method for preparing a chromatographic medium specially used for separating cannabidiol as claimed in claim 1, wherein in the step one, the mass of the catalyst is 0.1-5% of that of the cannabidiol.
5. The method for preparing a chromatographic medium special for separating cannabidiol as claimed in claim 1, wherein in the second step, the particle size of the porous amino silicon spheres is 10-500 μm.
6. The method for preparing a chromatographic medium specially used for separating cannabidiol as claimed in claim 1, wherein in the second step, the mass of the porous amino silicon spheres is 10-50 times of that of the cannabidiol.
7. The method for preparing a chromatographic medium dedicated for separation of cannabidiol as claimed in claim 1, wherein in step two, the organic solvent is one of xylene, carbon disulfide and dimethyl sulfoxide, preferably xylene.
8. The method for preparing a chromatographic medium specially used for separating cannabidiol as claimed in claim 1, wherein in step two, the type of the catalyst is one of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide, 1-hydroxybenzotriazole and N-hydroxysuccinimide, preferably 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide.
9. The method for preparing a chromatographic medium specially used for separating cannabidiol as claimed in claim 1, wherein in the second step, the mass of the catalyst is 0.1-5% of that of the cannabidiol.
10. The method for preparing a chromatographic medium special for separating cannabidiol as claimed in claim 1, wherein in the second step, the heating temperature is 70-85 ℃.
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| CN111135810A (en) * | 2020-01-22 | 2020-05-12 | 苏州汇通色谱分离纯化有限公司 | Preparation method of special chromatographic separation medium for cannabidiol separation |
| CN111330556A (en) * | 2020-03-07 | 2020-06-26 | 浙江肽达生物科技开发有限公司 | Preparation method of chromatographic separation medium |
| WO2020242969A1 (en) * | 2019-05-24 | 2020-12-03 | ImMutriX Therapeutics, Inc. | Chromatographic media and methods of making and using same |
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| WO2020242969A1 (en) * | 2019-05-24 | 2020-12-03 | ImMutriX Therapeutics, Inc. | Chromatographic media and methods of making and using same |
| CN111135810A (en) * | 2020-01-22 | 2020-05-12 | 苏州汇通色谱分离纯化有限公司 | Preparation method of special chromatographic separation medium for cannabidiol separation |
| CN111330556A (en) * | 2020-03-07 | 2020-06-26 | 浙江肽达生物科技开发有限公司 | Preparation method of chromatographic separation medium |
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