CN111233951A - Preparation method of orcinol glucoside - Google Patents
Preparation method of orcinol glucoside Download PDFInfo
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- CN111233951A CN111233951A CN202010201164.6A CN202010201164A CN111233951A CN 111233951 A CN111233951 A CN 111233951A CN 202010201164 A CN202010201164 A CN 202010201164A CN 111233951 A CN111233951 A CN 111233951A
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- orcinol
- glucoside
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- glucose
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- YTXIGTCAQNODGD-HENWMNBSSA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-6-(3-hydroxy-5-methylphenoxy)oxane-3,4,5-triol Chemical compound CC1=CC(O)=CC(OC2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 YTXIGTCAQNODGD-HENWMNBSSA-N 0.000 title claims abstract description 63
- YTXIGTCAQNODGD-LBELIVKGSA-N Orcinol glucoside Natural products CC1=CC(O)=CC(O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 YTXIGTCAQNODGD-LBELIVKGSA-N 0.000 title claims abstract description 62
- YTXIGTCAQNODGD-UHFFFAOYSA-N orcinol O-beta-D-glucopyranoside Natural products CC1=CC(O)=CC(OC2C(C(O)C(O)C(CO)O2)O)=C1 YTXIGTCAQNODGD-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- OIPPWFOQEKKFEE-UHFFFAOYSA-N orcinol Chemical compound CC1=CC(O)=CC(O)=C1 OIPPWFOQEKKFEE-UHFFFAOYSA-N 0.000 claims abstract description 175
- 235000001727 glucose Nutrition 0.000 claims abstract description 36
- 229930182478 glucoside Natural products 0.000 claims abstract description 27
- 150000008131 glucosides Chemical class 0.000 claims abstract description 26
- 239000003513 alkali Substances 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims abstract description 9
- 150000002304 glucoses Chemical class 0.000 claims abstract description 3
- 230000000850 deacetylating effect Effects 0.000 claims abstract 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 57
- 238000006243 chemical reaction Methods 0.000 claims description 57
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- 239000008103 glucose Substances 0.000 claims description 33
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 25
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 24
- 239000012074 organic phase Substances 0.000 claims description 23
- 230000006196 deacetylation Effects 0.000 claims description 21
- 238000003381 deacetylation reaction Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 230000013595 glycosylation Effects 0.000 claims description 15
- 238000006206 glycosylation reaction Methods 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 14
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 13
- YNSISDPVMBMWBJ-ZZVYKPCYSA-N (4s,5s,6r)-4,5-diacetyl-6-[(1r)-1,2-dihydroxyethyl]-4,5,6-trihydroxyoctane-2,3,7-trione Chemical compound CC(=O)C(=O)[C@@](O)(C(C)=O)[C@](O)(C(C)=O)[C@@](O)(C(C)=O)[C@H](O)CO YNSISDPVMBMWBJ-ZZVYKPCYSA-N 0.000 claims description 12
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 239000012043 crude product Substances 0.000 claims description 8
- 238000010898 silica gel chromatography Methods 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 229960001701 chloroform Drugs 0.000 claims description 6
- 239000005457 ice water Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 5
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical group [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000003444 phase transfer catalyst Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims description 2
- 238000010790 dilution Methods 0.000 claims description 2
- 239000012895 dilution Substances 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 229910052901 montmorillonite Inorganic materials 0.000 claims description 2
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 238000006386 neutralization reaction Methods 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- -1 orcinol glucosides Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910001923 silver oxide Inorganic materials 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 206010007027 Calculus urinary Diseases 0.000 description 1
- YTXIGTCAQNODGD-UJPOAAIJSA-N Orcinol glucoside Chemical compound CC1=CC(O)=CC(O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 YTXIGTCAQNODGD-UJPOAAIJSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 208000008281 urolithiasis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation method of orcinol glucoside, which comprises the steps of reacting orcinol with different substituted acetylated glucoses under the action of proper acid or alkali to obtain orcinol tetraacetylated glucoside, and deacetylating the orcinol tetraacetylated glucoside under the alkaline condition to obtain orcinol glucoside.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of three orcinol glucosides.
Background
Orcinol glucoside (sakakin, structure formula shown in formula I) and molecular formula C13H18O7Molecular weight 286.28, CAS number 21082-33-7.
Orcinol glucoside is mainly from rhizoma Curculiginis, is light yellow crystalline powder, and is soluble in water and organic solvent such as methanol, ethanol, DMSO, etc.
WO 2017/007346 a1, filed by the university of wakrafft, describes the synthesis of polyphenol glycoside compounds and their use in the treatment of urolithiasis, and reports the synthesis of orcinol glucoside. The patent uses orcinol and glucose as raw materials to prepare orcinol glucose. Firstly, converting glucose into penta-acetylated glucose, brominating with hydrobromic acid to obtain 1-bromo-tetra-acetylated glucose, condensing with orcinol under the action of silver oxide and quinoline to obtain orcinol tetra-acylated glucoside, and finally removing acetyl under the action of sodium methoxide to obtain orcinol glucoside. The synthesis method related to the patent has low yield, needs to use reagents such as silver oxide and the like, has high cost and cannot meet the requirement of drug development. Through literature search, other synthetic methods of orcinol glucoside are not disclosed.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide three new synthetic methods of orcinol glucoside, which are easy for industrial production.
In order to achieve the above purpose of the present invention, the present invention provides the following technical solutions:
the preparation process of orcinol glucoside includes the reaction of orcinol with different substituted acetylated glucoses under the action of proper acid or alkali to obtain orcinol tetraacetylated glucoside, deacetylation of orcinol tetraacetylated glucoside under alkali condition to obtain orcinol glucoside,
the preparation method of orcinol glucoside mainly comprises the following two reaction steps:
a first reaction step: reacting orcinol with different substituted acetylated glucose in a proper solvent under the action of proper acid or alkali to obtain orcinol tetraacetylated glucoside;
and a second reaction step: the orcinol tetraacetylated glucoside is subjected to the action of proper alkali to obtain orcinol glucoside.
The preparation method of orcinol glucoside mainly comprises the following three methods:
the method comprises the following steps: glycosylation/deacetylation of orcinol with pentaacetylated glucose under acidic conditions;
the second method comprises the following steps: glycosylation/deacetylation of orcinol and bromotetraacetylated glucose under alkaline conditions;
the third method comprises the following steps: glycosylation/deacetylation of orcinol with tetraacetylglucose trichloroacetimidate under acidic conditions.
Method I, a preparation method of orcinol glucoside, glycosylation/deacetylation of orcinol and pentaacetylated glucose under acidic condition,
the method comprises two steps: a first reaction step: reacting orcinol with pentaacetylated glucose in a proper solvent under the action of a proper acid to obtain orcinol tetraacetylated glucoside; and a second reaction step: the orcinol tetraacetylated glucoside is subjected to proper alkali action to obtain orcinol glucoside,
in the first reaction step, suitable acids are boron trifluoride diethyl etherate, tin tetrachloride, trimethylsilyl trifluoromethanesulfonate, zinc chloride and p-toluenesulfonic acid, and suitable solvents are: dichloromethane, trichloromethane, 1, 2-dichloroethane, toluene, benzene, etc., the reaction can be carried out at different temperatures; in reaction step two, suitable bases are: sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide.
The second method is a preparation method of orcinol glucoside, the glycosylation/deacetylation of orcinol and bromotetraacetylated glucose is carried out under the alkaline condition,
the method comprises two steps: a first reaction step: carrying out a reaction on orcinol and bromotetraacetylated glucose in a proper solvent under the action of proper alkali to obtain orcinol tetraacetylated glucoside; and a second reaction step: the orcinol tetraacetylated glucoside is subjected to proper alkali action to obtain orcinol glucoside,
in the first reaction step, appropriate alkali is sodium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate and the like, appropriate solvent is chloroform/water, dichloromethane/water and N, N-dimethylformamide, a certain amount of phase transfer catalyst can be added into a reaction system, appropriate phase transfer catalyst is benzyltriethylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride and 18 crown 6 ether, and in the second reaction step, appropriate alkali is: sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide.
Method III, a preparation method of orcinol glucoside, glycosylation/deacetylation of orcinol and tetraacetylglucose trichloroacetimidate under acidic condition,
the method comprises two steps: a first reaction step: reacting orcinol with tetraacetylglucose trichloroacetimidate glucose in a proper solvent under the action of proper alkali to obtain orcinol tetraacetylglucoside; and a second reaction step: the orcinol tetraacetylated glucoside is subjected to proper alkali action to obtain orcinol glucoside,
in the first reaction step, appropriate alkali is boron trifluoride ethyl ether, montmorillonite and trimethylsilyl trifluoromethanesulfonate, and appropriate solvent is: dichloromethane, trichloromethane, 1, 2-dichloroethane, toluene, benzene, in reaction step two, the appropriate base is: sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide.
More specifically, the present invention provides the following methods:
the preparation method of orcinol glucoside comprises the following steps of preparing orcinol glucoside/deacetylation of orcinol and pentaacetylated glucose under an acidic condition: under the protection of nitrogen, 186mg orcinol (1.5mmol) is dissolved in 4mL dichloromethane, 390mg penta-acetylated glucose (1mmol) and 139 μ L triethylamine (1mmol) are added into the dichloromethane in turn, 494 μ L boron trifluoride diethyl ether (4mmol) is slowly added into the orcinol after ice bath cooling to 0 ℃, the reaction mixture naturally rises to room temperature after the reagent addition is finished to react for 5h, the reaction mixture is poured into 10mL ice water, dichloromethane is extracted (5mL x 3), organic phases are combined, the organic phase is washed by saturated saline water and washed, dried by anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude orcinol tetra-acetylated glucoside, the crude orcinol tetra-acetylated glucoside is dissolved in 5mL methanol, 2.7mg sodium methoxide (0.05mmol) is added into the reaction mixture to react for 24h at room temperature, 5mL water is added to dilute the reaction solution, 5% hydrochloric acid solution is neutralized, methanol is removed under reduced pressure, n-butanol is used for extraction (5mL x 3), the organic, concentrating under reduced pressure to remove reaction liquid, and separating the crude product by silica gel column chromatography to obtain orcinol glucoside.
Preparation of orcinol glucoside, glycosylation/deacetylation of orcinol and bromotetraacetylated glucose under alkaline conditions preparation of orcinol glucoside, dissolving 248mg of orcinol (2mmol) in 10mL of sodium hydroxide (0.8N) aqueous solution, stirring for 30 minutes, dissolving 822mg of 1- α -bromo-2, 3,4, 6-tetraacetylated glucose (2mmol) and 148mg of tetrabutylammonium iodide (0.4mmol) in 10mL of dichloromethane, slowly adding to the above reaction solution, reacting at room temperature for 3.5 hours, adjusting pH of the reaction solution to neutral using 5% hydrochloric acid, extracting with dichloromethane (10 mL. times.3), combining the organic phases, washing the organic phase with saturated sodium bicarbonate and saturated sodium chloride solutions in order, drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the solvent to obtain crude orcinol glucoside, adding 5mL of methanol, adding 5.4mg of sodium methoxide (0.1mmol) thereto, reacting at room temperature for 24 hours, adding 10mL of water for dilution, removing the solvent from the reaction solution by reduced pressure concentration to obtain crude orcinol glucoside, separating the crude orcinol glucoside by using N-butanol, and concentrating the crude orcinol gel column under reduced pressure to obtain N-butanol, and concentrating the crude orcinol column.
Preparation method of orcinol glucoside comprises preparing orcinol glucoside/deacetylation of orcinol and tetraacetylglucose trichloroacetimidate under acidic condition: under nitrogen protection, 124mg orcinol (1mmol) and 590mg tetraacetylglucose trichloroacetimidate (1.2mmol) are dissolved in 4mL dry dichloromethane, cooled to 0 ℃ in an ice bath, 12.4. mu.L boron trifluoride diethyl ether (0.1mmol) is slowly added thereto, the reaction mixture is poured into 10mL ice water after 3 hours at 0 ℃, extracting with dichloromethane (5mL × 3), mixing organic phases, washing the organic phase with saturated saline, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain coarse orcinol tetraacetylglucoside, dissolving the coarse orcinol tetraacetylglucoside in 5mL of methanol, 2.7mg of sodium methoxide (0.05mmol) was added thereto, and the mixture was reacted at room temperature for 24 hours, then 5mL of water was added to dilute the reaction mixture, followed by neutralization with a 5% hydrochloric acid solution, removing methanol under reduced pressure, extracting with n-butanol (5mL × 3), mixing organic phases, concentrating under reduced pressure to remove n-butanol, and separating the crude product by silica gel column chromatography to obtain orcinol glucoside.
The preparation method of orcinol glucoside provided by the invention overcomes the technical defect that the extraction cost of orcinol glucoside from plants is high, the raw materials of the method are easy to obtain, the yield is high, the method is suitable for industrialization, and a new synthesis method is provided for the preparation of orcinol glucoside.
Detailed Description
In order to understand the present invention, the following examples are provided to further illustrate the essence of the present invention, but not to limit the present invention.
Example 1
The orcinol glucoside is prepared by the glycosylation/deacetylation of orcinol and pentaacetylated glucose under acidic condition.
186mg orcinol (1.5mmol) was dissolved in 4mL dichloromethane under nitrogen protection, 390mg pentaacetylated glucose (1mmol) and 139. mu.L triethylamine (1mmol) were added sequentially thereto, 494. mu.L boron trifluoride diethyl ether (4mmol) was slowly added thereto after cooling in an ice bath to 0 ℃, and the reaction mixture naturally warmed to room temperature after completion of the reagent addition and reacted for 5 h. The reaction mixture was poured into 10mL of ice water, extracted with dichloromethane (5mL × 3), the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude orcinol tetraacetylglucoside. Dissolving the crude product in 5mL of methanol, adding 2.7mg of sodium methoxide (0.05mmol) into the methanol, reacting the mixture at room temperature for 24 hours, adding 5mL of water to dilute the reaction solution, neutralizing the reaction solution with 5% hydrochloric acid solution, removing the methanol under reduced pressure, extracting the reaction solution with n-butanol (5 mL. times.3), combining organic phases, concentrating the organic phases under reduced pressure to remove the reaction solution, and separating the crude product by silica gel column chromatography to obtain 152mg of orcinol glucoside, wherein the yield is 53%.
Example 2
The orcinol glucoside is prepared by the glycosylation/deacetylation of orcinol and bromotetraacetylated glucose under the alkaline condition.
Dissolving 248mg orcinol (2mmol) in 10mL of sodium hydroxide (0.8N) aqueous solution, stirring for 30 minutes, dissolving 822mg of 1- α -bromo-2, 3,4, 6-tetraacetylated glucose (2mmol) and 148mg of tetrabutylammonium iodide (0.4mmol) in 10mL of dichloromethane, slowly adding to the reaction solution, reacting at room temperature for 3.5 hours, adjusting the pH of the reaction solution to neutrality using 5% hydrochloric acid, extracting with dichloromethane (10 mL. times.3), combining the organic phases, washing the organic phase with saturated sodium bicarbonate and saturated sodium chloride solutions in sequence, drying over anhydrous sodium sulfate, concentrating under reduced pressure to remove the solvent to obtain crude orcinol tetraacetylated glucoside, dissolving the crude orcinol in 5mL of methanol, adding 5.4mg of sodium methoxide (0.1mmol) thereto, reacting at room temperature for 24 hours, adding 10mL of water to dilute the reaction solution, neutralizing with 5% hydrochloric acid solution, removing methanol under reduced pressure, extracting with N-butanol (10 mL. times.3), combining the organic phases, concentrating under reduced pressure to remove N-butanol, and separating the crude orcinol by silica gel chromatography to obtain 74 mg of orcinol.
Example 3
The glycosylation/deacetylation of orcinol with tetraacetylglucose trichloroacetimidate under acidic conditions produces orcinol glucoside.
Under the protection of nitrogen, 124mg orcinol (1mmol) and 590mg tetraacetylglucose trichloroacetimidate (1.2mmol) are dissolved in 4mL of dry dichloromethane, cooled to 0 ℃ in an ice bath, 12.4. mu.L of boron trifluoride diethyl etherate (0.1mmol) is slowly added thereto, after reaction at 0 ℃ for 3 hours, the reaction mixture is poured into 10mL of ice water, dichloromethane is extracted (5 mL. times.3), the organic phases are combined, the organic phases are washed with saturated saline solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude orcinol tetraacetylglucoside. Dissolving the crude product in 5mL of methanol, adding 2.7mg of sodium methoxide (0.05mmol) into the methanol, reacting the mixture at room temperature for 24 hours, adding 5mL of water to dilute the reaction solution, neutralizing the reaction solution with 5% hydrochloric acid solution, removing the methanol under reduced pressure, extracting the reaction solution with n-butanol (5 mL. times.3), combining organic phases, removing the n-butanol under reduced pressure, and separating the obtained crude product by silica gel column chromatography to obtain 186mg of orcinol glucoside, wherein the yield is 65%.
The method of the present invention has been described by way of specific examples. It will be apparent to those skilled in the art that other modifications, variations, and equivalents of the materials and process conditions used therein may be suitably made in view of the teachings of the present invention without departing from the scope thereof, and therefore, such alternatives and modifications are to be considered as included within the scope of the invention.
Claims (9)
1. The preparation process of orcinol glucoside includes the reaction of orcinol with different substituted acetylated glucoses under the action of proper acid or alkali to obtain orcinol tetraacetylated glucoside, deacetylation of orcinol tetraacetylated glucoside under alkali condition to obtain orcinol glucoside,
2. the method of preparing orcinol glucoside according to claim 1, characterized in that it essentially comprises the following two reaction steps:
a first reaction step: reacting orcinol with different substituted acetylated glucose in a proper solvent under the action of proper acid or alkali to obtain orcinol tetraacetylated glucoside;
and a second reaction step: the orcinol tetraacetylated glucoside is subjected to the action of proper alkali to obtain orcinol glucoside.
3. The method for preparing orcinol glucoside according to claim 1 or 2, characterized in that it is mainly divided into the following three methods:
the method comprises the following steps: glycosylation/deacetylation of orcinol with pentaacetylated glucose under acidic conditions;
the second method comprises the following steps: glycosylation/deacetylation of orcinol and bromotetraacetylated glucose under alkaline conditions;
the third method comprises the following steps: glycosylation/deacetylation of orcinol with tetraacetylglucose trichloroacetimidate under acidic conditions.
4. Preparation method of orcinol glucoside comprises glycosidating/deacetylating orcinol and pentaacetylated glucose under acidic condition,
the method comprises two steps: a first reaction step: reacting orcinol with pentaacetylated glucose in a proper solvent under the action of a proper acid to obtain orcinol tetraacetylated glucoside; and a second reaction step: the orcinol tetraacetylated glucoside is subjected to proper alkali action to obtain orcinol glucoside,
in the first reaction step, suitable acids are boron trifluoride diethyl etherate, tin tetrachloride, trimethylsilyl trifluoromethanesulfonate, zinc chloride and p-toluenesulfonic acid, and suitable solvents are: dichloromethane, trichloromethane, 1, 2-dichloroethane, toluene, benzene, etc., the reaction can be carried out at different temperatures; in reaction step two, suitable bases are: sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide.
5. The preparation method of orcinol glucoside comprises the glycosylation/deacetylation of orcinol and bromotetraacetylated glucose under alkaline condition,
the method comprises two steps: a first reaction step: carrying out a reaction on orcinol and bromotetraacetylated glucose in a proper solvent under the action of proper alkali to obtain orcinol tetraacetylated glucoside; and a second reaction step: the orcinol tetraacetylated glucoside is subjected to proper alkali action to obtain orcinol glucoside,
in the first reaction step, appropriate alkali is sodium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate and the like, appropriate solvent is chloroform/water, dichloromethane/water and N, N-dimethylformamide, a certain amount of phase transfer catalyst can be added into a reaction system, appropriate phase transfer catalyst is benzyltriethylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride and 18 crown 6 ether, and in the second reaction step, appropriate alkali is: sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide.
6. A method for preparing orcinol glucoside comprises glycosidating/deacetylating orcinol and tetraacetylglucose trichloroacetimidate under acidic condition,
the method comprises two steps: a first reaction step: reacting orcinol with tetraacetylglucose trichloroacetimidate glucose in a proper solvent under the action of proper alkali to obtain orcinol tetraacetylglucoside; and a second reaction step: the orcinol tetraacetylated glucoside is subjected to proper alkali action to obtain orcinol glucoside,
in the first reaction step, appropriate alkali is boron trifluoride ethyl ether, montmorillonite and trimethylsilyl trifluoromethanesulfonate, and appropriate solvent is: dichloromethane, trichloromethane, 1, 2-dichloroethane, toluene, benzene, in reaction step two, the appropriate base is: sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide.
7. The preparation method of orcinol glucoside comprises the following steps of preparing orcinol glucoside/deacetylation of orcinol and pentaacetylated glucose under an acidic condition: under the protection of nitrogen, 186mg orcinol (1.5mmol) is dissolved in 4mL dichloromethane, 390mg penta-acetylated glucose (1mmol) and 139 μ L triethylamine (1mmol) are added into the dichloromethane in turn, 494 μ L boron trifluoride diethyl ether (4mmol) is slowly added into the orcinol after ice bath cooling to 0 ℃, the reaction mixture naturally rises to room temperature after the reagent addition is finished to react for 5h, the reaction mixture is poured into 10mL ice water, dichloromethane is extracted (5mL x 3), organic phases are combined, the organic phase is washed by saturated saline water and washed, dried by anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude orcinol tetra-acetylated glucoside, the crude orcinol tetra-acetylated glucoside is dissolved in 5mL methanol, 2.7mg sodium methoxide (0.05mmol) is added into the reaction mixture to react for 24h at room temperature, 5mL water is added to dilute the reaction solution, 5% hydrochloric acid solution is neutralized, methanol is removed under reduced pressure, n-butanol is used for extraction (5mL x 3), the organic, concentrating under reduced pressure to remove reaction liquid, and separating the crude product by silica gel column chromatography to obtain orcinol glucoside.
8. Preparation of orcinol glucoside, glycosylation/deacetylation of orcinol and bromotetraacetylated glucose under alkaline conditions preparation of orcinol glucoside, dissolving 248mg of orcinol (2mmol) in 10mL of sodium hydroxide (0.8N) aqueous solution, stirring for 30 minutes, dissolving 822mg of 1- α -bromo-2, 3,4, 6-tetraacetylated glucose (2mmol) and 148mg of tetrabutylammonium iodide (0.4mmol) in 10mL of dichloromethane, slowly adding to the above reaction solution, reacting at room temperature for 3.5 hours, adjusting pH of the reaction solution to neutral using 5% hydrochloric acid, extracting with dichloromethane (10 mL. times.3), combining the organic phases, washing the organic phase with saturated sodium bicarbonate and saturated sodium chloride solutions in order, drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove the solvent to obtain crude orcinol glucoside, adding 5mL of methanol, adding 5.4mg of sodium methoxide (0.1mmol) thereto, reacting at room temperature for 24 hours, adding 10mL of water for dilution, removing the solvent from the reaction solution by reduced pressure concentration to obtain crude orcinol glucoside, separating the crude orcinol glucoside by using N-butanol, and concentrating the crude orcinol gel column under reduced pressure to obtain N-butanol, and concentrating the crude orcinol column.
9. Preparation method of orcinol glucoside comprises preparing orcinol glucoside/deacetylation of orcinol and tetraacetylglucose trichloroacetimidate under acidic condition: under nitrogen protection, 124mg orcinol (1mmol) and 590mg tetraacetylglucose trichloroacetimidate (1.2mmol) are dissolved in 4mL dry dichloromethane, cooled to 0 ℃ in an ice bath, 12.4. mu.L boron trifluoride diethyl ether (0.1mmol) is slowly added thereto, the reaction mixture is poured into 10mL ice water after 3 hours at 0 ℃, extracting with dichloromethane (5mL × 3), mixing organic phases, washing the organic phase with saturated saline, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain coarse orcinol tetraacetylglucoside, dissolving the coarse orcinol tetraacetylglucoside in 5mL of methanol, 2.7mg of sodium methoxide (0.05mmol) was added thereto, and the mixture was reacted at room temperature for 24 hours, then 5mL of water was added to dilute the reaction mixture, followed by neutralization with a 5% hydrochloric acid solution, removing methanol under reduced pressure, extracting with n-butanol (5mL × 3), mixing organic phases, concentrating under reduced pressure to remove n-butanol, and separating the crude product by silica gel column chromatography to obtain orcinol glucoside.
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| CN113667655A (en) * | 2021-08-24 | 2021-11-19 | 云南农业大学 | Curculigo orchioides glycosyltransferase Co84A-471 gene and application thereof in preparation of orcinol glucoside |
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