CN113214339A - Panaxadiol derivatives, preparation method and medical application thereof - Google Patents
Panaxadiol derivatives, preparation method and medical application thereof Download PDFInfo
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- CN113214339A CN113214339A CN202110298895.1A CN202110298895A CN113214339A CN 113214339 A CN113214339 A CN 113214339A CN 202110298895 A CN202110298895 A CN 202110298895A CN 113214339 A CN113214339 A CN 113214339A
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- panaxadiol
- hexadecahydro
- pentamethyl
- pyran
- hydroxy
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- PVLHOJXLNBFHDX-XHJPDDKBSA-N Panaxadiol Chemical class C[C@]1([C@H]2CC[C@@]3([C@@H]2[C@H](O)C[C@H]2[C@]3(CC[C@H]3C(C)(C)[C@@H](O)CC[C@@]32C)C)C)CCCC(C)(C)O1 PVLHOJXLNBFHDX-XHJPDDKBSA-N 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- SYFJYASKXNAXKC-UHFFFAOYSA-N Panaxadiol Natural products CC1(C)CCCC(O1)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5CCC34C SYFJYASKXNAXKC-UHFFFAOYSA-N 0.000 claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- -1 panaxadiol compound Chemical class 0.000 claims abstract description 11
- 230000005779 cell damage Effects 0.000 claims abstract description 9
- 208000037887 cell injury Diseases 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 210000002569 neuron Anatomy 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 8
- 150000002540 isothiocyanates Chemical class 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 5
- 150000002513 isocyanates Chemical class 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- ZZEKCIVZXFBRJV-UHFFFAOYSA-N (3-fluorophenyl) carbamate Chemical compound NC(=O)OC1=CC=CC(F)=C1 ZZEKCIVZXFBRJV-UHFFFAOYSA-N 0.000 claims description 3
- CCENBZDJMALWCH-UHFFFAOYSA-N (4-chlorophenyl) carbamate Chemical compound NC(=O)OC1=CC=C(Cl)C=C1 CCENBZDJMALWCH-UHFFFAOYSA-N 0.000 claims description 3
- NIHHYKUHSZFXTC-UHFFFAOYSA-N (4-methoxyphenyl) carbamate Chemical compound COC1=CC=C(OC(N)=O)C=C1 NIHHYKUHSZFXTC-UHFFFAOYSA-N 0.000 claims description 3
- 230000000324 neuroprotective effect Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- VJZNUICECYWOFV-UHFFFAOYSA-N o-phenyl carbamothioate Chemical compound NC(=S)OC1=CC=CC=C1 VJZNUICECYWOFV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 230000007131 anti Alzheimer effect Effects 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000004643 cyanate ester Substances 0.000 claims 1
- 230000036541 health Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 2
- 210000005036 nerve Anatomy 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 56
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- ANJYDSPMBISEHY-UHFFFAOYSA-N (4-fluorophenyl) carbamate Chemical compound NC(=O)OC1=CC=C(F)C=C1 ANJYDSPMBISEHY-UHFFFAOYSA-N 0.000 description 2
- RHNSSYGTJAAVCR-UHFFFAOYSA-N (4-methylphenyl)carbamic acid Chemical compound CC1=CC=C(NC(O)=O)C=C1 RHNSSYGTJAAVCR-UHFFFAOYSA-N 0.000 description 2
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 2
- 241000208340 Araliaceae Species 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000008434 ginseng Nutrition 0.000 description 2
- 229940089161 ginsenoside Drugs 0.000 description 2
- 229930182494 ginsenoside Natural products 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 241000208173 Apiaceae Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 241000208343 Panax Species 0.000 description 1
- 235000002791 Panax Nutrition 0.000 description 1
- 240000004371 Panax ginseng Species 0.000 description 1
- 235000002789 Panax ginseng Nutrition 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- OORMXZNMRWBSTK-LGFJJATJSA-N dammarane Chemical compound C1CCC(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@H]([C@H](C)CCCC(C)C)[C@H]4CC[C@@H]3[C@]21C OORMXZNMRWBSTK-LGFJJATJSA-N 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Abstract
The invention provides a panaxadiol derivative which is a novel compound. The invention also provides a preparation method of the panaxadiol compound, and the method has the advantages of rich raw material sources, simple reaction process operation, and cheap and easily obtained reagents. The compound of the invention is tested by a nerve protection effect experiment of in vitro anti-Abeta 25-35 induced PC12 cell injury, and the result shows that the panaxadiol derivatives of the invention have obvious nerve cell protection effect and can be used for preparing medicines for preventing or treating nerve cell injury diseases.
Description
Technical Field
The invention discloses a kind of panaxadiol derivative, and also provides a preparation method of the panaxadiol derivative; the invention further provides medical application of the panaxadiol derivative, belonging to the field of chemical medicine.
Background
Panaxane ginsenoside is a tetracyclic triterpene compound obtained by hydrolyzing dammarane ginsenoside separated from Ginseng radix (Panax ginseng C.A.Mey) of Panax of Araliaceae of Umbelliferae. Panaxadiol (Panaxadiol, structure formula shown in figure)I shown as the formula I, which is called PD hereinafter) and has the chemical name of (3S, 8R, 10R, 12R, 14R) -4,4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopentyl [ a]Phenanthrene-3, 12-diol, formula: c30H52O3Molecular weight 460.74.
Disclosure of Invention
The invention aims to provide a novel panaxadiol derivative and a preparation method thereof.
The invention also aims to provide application of the compounds in preventing or treating nerve cell injury diseases.
The invention relates to a panaxadiol derivative which has a structure shown in a formula II:
wherein, when X is oxygen, R is the following group:
(A) aromatic hydrocarbons: phenyl, 4-chlorophenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-methylphenyl, 3-fluorophenyl, benzyl;
(B) alkane: ethyl, propyl, isopropyl, heptyl, hexyl, cyclohexyl, allyl:
when X is sulfur, R is phenyl:
the compounds having the above general formula II are:
IIa: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylbenzylcarbamate;
IIb: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylphenylcarbamate;
IIc: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl (4-chlorophenyl) carbamate;
IId: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl (4-methoxyphenyl) carbamate;
IIe: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthreneanthracen-3-yl (4-fluorophenyl) carbamate;
IIf: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl p-tolylcarbamate;
IIj: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl (3-fluorophenyl) carbamate;
IIh: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylcarbamic acid ethyl ester;
IIi: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylheptylcarbamate;
IIg: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylisopropylcarbamate;
IIk: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylhexylcarbamate;
IIl: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopentyl [ a ] phenanthryl-3-cyclohexylcarbamate;
IIm: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylallylcarbamate;
IIn: (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylpropylcarbamate;
IIo: o- ((3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R-2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl) phenylthiocarbamate;
the invention also provides a synthetic route of the compound of the general formula II as follows:
weighing panaxadiol and dissolving in a solvent, adding isocyanate or isothiocyanate under low-temperature stirring, wherein the molar number of the isocyanate or isothiocyanate is at least 2 times that of the panaxadiol, adding a catalyst, stirring and reacting under the protection of nitrogen, detecting by TLC, evaporating the solvent in a solvent system after the reaction, and performing chromatographic separation on the residual solid silica gel column (chloroform: methanol is 100: 1) or preparing by a thin layer to obtain the compound of the general formula II;
in the method for preparing the panaxadiol derivative, the catalyst is any one of sodium hydrogen, triethylamine and N, N-diisopropylethylamine. The solvent is one of tetrahydrofuran, toluene and chloroform, and the mole ratio of the panaxadiol to the solvent is 0.05-0.2;
in the method for preparing the panaxadiol derivative, the ratio of the mole number of the panaxadiol to the mole number of the isocyanate or the isothiocyanate is 1-10: 1, the molar ratio of the panaxadiol to the catalyst is 1-10, and the reaction temperature is 80-120 ℃.
The derivative disclosed by the invention adopts an MTT method to determine A beta25-35Induce neuroprotective effects of PC12 cell injury, the structure indicates the tested chemotherapyThe compound shows better nerve cell protection effect.
The invention also provides application of the panaxadiol derivative in preparing a medicament for treating nerve cell protection.
The invention also provides application of the panaxadiol derivative in preparation of an anti-Alzheimer disease drug or a health-care product.
The method for preparing the panaxadiol derivative is simple, high in purity, low in cost and suitable for industrial production.
The invention has the positive effects that:
a panaxadiol derivative is disclosed, which is a new kind of compound. Simultaneously, the method for preparing the panaxadiol compound has the advantages of rich raw material sources, simple reaction process operation and cheap and easily obtained reagents. The compounds of the invention are directed against Abeta in vitro25-35The result of the experiment test of the nerve protection effect of inducing the PC12 cell damage shows that the panaxadiol derivatives have obvious nerve cell protection effect and can be used for preparing the medicines for preventing or treating the nerve cell damage diseases.
The specific implementation mode is as follows:
the following examples illustrate the invention in detail, but the practice of the invention is not limited thereto; the reagents and raw materials used in the invention are commercially available, and are analytically pure without special labels.
Example 1
IIa (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylbenzylcarbamate;
placing panaxadiol (55.00mg) in 10mL anhydrous toluene, slowly adding benzyl isocyanate or isothiocyanate (32mg), TEA or DIEA (33 μ L) dropwise under ice bath, removing ice bath, stirring at 100 deg.C under nitrogen protection for 12-15 ℃And (4) hours. TCL detection reaction until the material disappeared, toluene (3X 10mL) extraction three times, saturated NaCl (2X 10mL) solution after washing, anhydrous Na2SO4Drying, filtering under reduced pressure, and spin-drying to obtain crude product. Purification by silica gel chromatography using methanol/dichloromethane (100: 1) as eluent gave compound IIa. The yield was 63%.1H NMR(300MHz,CDCl3)δ7.38–7.27(m,5H),6.70(s,1H),4.92(s,1H), 4.49–4.28(m,3H),3.56(td,J＝10.0,4.9Hz,1H),2.33(s,1H),1.99–1.85(m,2H),1.83– 1.67(m,4H),1.66–1.35(m,11H),1.34–1.22(m,10H),1.19(s,3H),1.11–1.02(m,2H), 0.98(s,3H),0.89(s,9H),0.80(s,3H).13C NMR(125MHz,CDCl3)δ156.79,138.78, 128.65,127.54,127.42,81.46,76.66,73.10,69.89,56.02,54.73,51.21,49.84,49.19,45.05, 39.82,38.60,38.10,37.04,36.46,35.75,34.84,33.03,31.14,30.57,27.99,27.15,25.17, 24.17,19.43,18.20,17.07,16.52,16.29,16.18,15.64。
Example 2
IIb: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylphenylcarbamate;
the preparation method is the same as that of example 1; the yield was 57%.1H NMR(300MHz,CDCl3)δ7.32(d,J＝7.6Hz, 2H),7.24(d,J＝7.4Hz,2H),6.97(t,J＝7.2Hz,1H),6.49(s,1H),6.19(s,1H),4.41(dd,J＝11.4,4.7Hz,1H),3.48(td,J＝10.1,4.8Hz,1H),1.93–1.78(m,2H),1.78–1.60(m,5H), 1.59–1.35(m,11H),1.32–1.22(m,2H),1.20(s,4H),1.15(s,4H),1.12(s,3H),1.08–0.96 (m,2H),0.92(s,3H),0.86(s,3H),0.85(s,3H),0.82(s,3H),0.80(s,3H).13C NMR(125 MHz,CDCl3)δ153.62,138.17,129.02,123.19,118.55,81.93,76.66,73.10,69.88,56.05, 54.74,51.22,49.85,49.20,39.84,38.61,38.10,37.07,36.46,35.76,34.83,33.03,31.14, 30.59,28.05,27.16,25.18,24.11,19.44,18.22,17.08,16.62,16.29,16.20,15.66。
Example 3
IIc: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl (4-chlorophenyl) carbamate;
the preparation method is the same as that of example 1; the yield was 64%.1H NMR(300MHz,CDCl3)δ7.35(d,J＝8.5Hz,2H), 7.28–7.22(m,2H),6.60(s,1H),6.27(s,1H),4.47(dd,J＝11.4,4.3Hz,1H),3.54(td,J＝10.1,4.9Hz,1H),2.01–1.85(m,2H),1.85–1.67(m,5H),1.67–1.39(m,11H),1.38–1.30 (m,2H),1.27(s,4H),1.22(s,4H),1.18(s,3H),1.14–1.03(m,2H),0.99(s,3H),0.92(s, 3H),0.91(s,3H),0.89(s,3H),0.86(s,3H).13C NMR(125MHz,CDCl3)δ153.46,136.80, 129.00,128.17,119.76,82.23,76.66,73.11,69.87,56.04,54.74,51.22,49.85,49.20,39.84, 38.59,38.09,37.06,36.46,35.76,34.82,33.03,31.14,30.59,28.05,27.17,25.18,24.09, 19.44,18.21,17.08,16.61,16.29,16.19,15.66。
Example 4
IId: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl (4-methoxyphenyl) carbamate;
the preparation method is the same as that of example 1; the yield was 54%.1H NMR(300MHz,CDCl3)δ8.35(s,1H),7.65(d,J ＝9.0Hz,2H),7.04(d,J＝9.0Hz,2H),6.27(s,1H),4.92–4.76(m,1H),3.88(s,3H),3.56 (td,J＝10.8,5.4Hz,1H),2.02–1.89(m,2H),1.87–1.74(m,5H),1.71–1.39(m,11H), 1.39–1.31(m,2H),1.27(s,4H),1.23(s,4H),1.19(s,3H),1.17–1.13(m,1H),1.10–1.06 (m,1H),1.05–1.02(m,3H),1.00(s,3H),0.96(s,3H),0.95(s,3H),0.90(s,3H).13C NMR (125MHz,CDCl3)δ155.83,153.94,131.28,120.39,114.23,81.76,76.66,73.10,69.88, 56.05,55.52,54.74,51.22,49.85,49.20,39.84,38.61,38.10,37.06,36.47,35.76,34.84, 33.03,31.14,30.59,28.05,27.16,25.18,24.13,19.44,18.22,17.08,16.61,16.29,16.19, 15.66。
Example 5
IIe: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthreneanthracen-3-yl (4-fluorophenyl) carbamate;
the preparation method is the same as that of example 1; the yield was 59%.1H NMR(300MHz,CDCl3)δ7.34(s,2H),6.99(t,J ＝8.6Hz,2H),6.53(s,1H),6.26(s,1H),4.46(dd,J＝11.5,4.4Hz,1H),3.54(td,J＝10.2, 5.0Hz,1H),2.00–1.84(m,2H),1.83–1.66(m,5H),1.65–1.41(m,11H),1.39–1.29(m, 2H),1.26(s,4H),1.22(s,4H),1.18(s,3H),1.14–1.02(m,2H),0.98(s,3H),0.92(s,3H), 0.91(s,3H),0.89(s,3H),0.86(s,3H).13C NMR(125MHz,CDCl3)δ158.87(d,JCF＝242.2 Hz),153.76,134.17,120.25,115.69,82.09,76.66,73.11,69.87,56.03,54.73,51.21,49.85, 49.20,39.83,38.59,38.09,37.06,36.46,35.76,34.82,33.03,31.14,30.59,28.05,27.16, 25.17,24.11,19.44,18.21,17.07,16.60,16.29,16.19,15.66。
Example 6
IIf: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl p-tolylcarbamate;
the preparation method is the same as that of example 1; the yield was 69%.1H NMR(300MHz,CDCl3)δ7.27(d,J＝5.4Hz, 2H),7.10(d,J＝8.3Hz,2H),6.48(s,1H),6.26(s,1H),4.46(dd,J＝11.5,4.2Hz,1H),3.54 (td,J＝10.1,5.1Hz,1H),2.30(s,3H),2.00–1.85(m,2H),1.83–1.69(m,4H),1.68–1.40 (m,12H),1.39–1.30(m,2H),1.26(s,4H),1.22(s,4H),1.18(s,3H),1.14–1.02(m,2H), 0.98(s,3H),0.93(s,3H),0.91(s,3H),0.89(s,3H),0.86(s,3H).13C NMR(125MHz, CDCl3)δ153.72,135.57,132.71,129.49,118.64,81.77,76.66,73.10,69.88,56.05,54.73, 51.21,49.85,49.20,39.83,38.61,38.09,37.06,36.46,35.76,34.83,33.03,31.14,30.58, 28.05,27.16,25.18,24.12,20.73,19.44,18.21,17.08,16.62,16.29,16.19,15.66。
Example 7
IIj: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl (3-fluorophenyl) carbamate;
the preparation method is the same as that of example 1; the yield was 53%.1H NMR(300MHz,DMSO-d6)δ9.72(s,1H),7.40 (d,J＝11.4Hz,1H),7.28(dt,J＝17.3,8.6Hz,2H),6.79(t,J＝7.8Hz,1H),5.60(s,1H), 4.47–4.27(m,1H),3.43–3.35(m,1H),1.90–1.61(m,8H),1.60–1.36(m,10H),1.34– 1.22(m,3H),1.19(s,4H),1.11(s,6H),1.06–0.97(m,2H),0.92(s,3H),0.87(s,9H),0.84 (s,3H).13C NMR(125MHz,DMSO-d6)δ162.38(d,JCF＝240.8Hz),153.53,141.27, 130.33,114.01,108.71,108.54,80.73,76.23,72.51,69.16,55.27,54.14,50.74,49.01,48.94, 40.19,38.10,37.82,36.55,35.94,35.18,34.38,32.79,30.66,30.36,27.77,27.12,24.60, 23.79,19.28,17.79,16.89,16.60,16.00,15.80,15.45。
Example 8
IIh: preparation of ethyl (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylcarbamate;
the preparation method is the same as that of example 1; the yield was 54%.1H NMR(300MHz,CDCl3)δ6.25(s,1H),4.56(s, 1H),4.35(dd,J＝11.3,4.6Hz,1H),3.53(td,J＝10.3,5.1Hz,1H),3.30–3.12(m,2H),1.99 –1.84(m,2H),1.83–1.66(m,4H),1.64–1.39(m,12H),1.38–1.28(m,2H),1.26(s,4H), 1.22(s,4H),1.18(s,3H),1.16–1.10(m,3H),1.09–1.01(m,2H),0.96(s,3H),0.93–0.85 (m,9H),0.81(s,3H).13C NMR(125MHz,CDCl3)δ156.67,80.96,76.66,73.09,69.89, 56.02,54.73,51.22,49.84,49.19,45.42,39.82,38.61,38.09,37.04,36.46,35.76,34.84, 33.03,31.14,30.58,27.99,27.16,25.18,24.18,19.43,18.21,17.07,16.52,16.29,16.18, 15.65,15.31。
Example 9
IIi: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylheptyl carbamate;
the preparation method is the same as that of example 1; the yield was 57%.1H NMR(300MHz,CDCl3)δ6.24(s,1H),4.59(s, 1H),4.36(dd,J＝10.3,3.6Hz,1H),3.53(td,J＝10.3,5.1Hz,1H),3.16(s,2H),2.01–1.84 (m,2H),1.83–1.37(m,18H),1.27(s,15H),1.22(s,3H),1.18(s,3H),1.09–1.01(m,2H), 0.98(s,3H),0.88(s,12H),0.81(s,3H).13C NMR(125MHz,CDCl3)δ156.79,80.94,76.65, 73.08,69.89,56.02,54.73,51.21,49.84,49.20,40.99,39.82,38.61,38.10,37.04,36.46, 35.76,34.84,33.03,31.75,31.14,30.58,30.07,28.96,27.98,27.16,26.73,25.17,24.18, 22.59,19.43,18.21,17.07,16.53,16.29,16.18,15.65,14.07。
Example 10
IIg: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylisopropylcarbamate;
the preparation method is the same as that of example 1; the yield was 63%.1H NMR(300MHz,CDCl3)δ6.25(s,1H),4.51– 4.28(m,2H),3.80(s,1H),3.53(td,J＝10.2,5.0Hz,1H),2.01–1.84(m,2H),1.82–1.66 (m,5H),1.65–1.28(m,13H),1.26(s,4H),1.22(s,4H),1.18(s,3H),1.16(s,3H),1.14(s, 3H),1.11–1.01(m,2H),0.98(s,3H),0.88(s,9H),0.82(s,3H).13C NMR(125MHz,CDCl3) δ155.97,80.80,76.65,73.08,69.89,56.03,54.73,51.21,49.84,49.19,42.89,42.10,39.82, 38.61,38.10,37.04,36.46,35.75,34.84,33.03,31.13,30.58,27.99,27.16,25.17,24.17, 23.15,19.43,18.21,17.07,16.55,16.29,16.18,15.64。
Example 11
IIk: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylhexylcarbamate;
the preparation method is the same as that of example 1; the yield was 54%.1H NMR(300MHz,CDCl3)δ6.25(s,1H),4.59(s, 1H),4.41–4.27(m,1H),3.53(td,J＝10.1,5.1Hz,1H),3.16(s,2H),2.01–1.84(m,2H), 1.83–1.35(m,19H),1.29(s,7H),1.27(s,4H),1.22(s,4H),1.18(s,3H),1.11–1.01(m, 2H),0.98(s,3H),0.88(s,12H),0.81(s,3H).13C NMR(125MHz,CDCl3)δ156.79,80.93, 76.65,73.08,69.89,56.02,54.73,51.21,49.84,49.20,40.99,39.82,38.61,38.10,37.04, 36.46,35.75,34.84,33.03,31.49,31.13,30.58,30.03,27.98,27.16,26.44,25.17,24.18, 22.56,19.43,18.21,17.07,16.52,16.29,16.18,15.64,14.01。
Example 12
IIl: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopentyl [ a ] phenanthryl-3-cyclohexylcarbamate;
the preparation was carried out as in example 1, giving a yield of 65%.1H NMR(300MHz,CDCl3)δ6.24(s,1H),4.48(s, 1H),4.35(dd,J＝11.3,4.4Hz,1H),3.53(td,J＝10.3,5.1Hz,2H),2.00–1.83(m,4H),1.82 –1.66(m,7H),1.65–1.29(m,15H),1.26(s,4H),1.22(s,4H),1.18(s,4H),1.16–1.00(m, 5H),0.98(s,3H),0.88(s,9H),0.82(s,3H).13C NMR(125MHz,CDCl3)δ155.98,80.76, 76.65,73.08,69.89,56.02,54.73,51.22,49.83,49.70,49.20,39.82,38.61,38.11,37.04, 36.46,35.75,34.84,33.54,33.03,31.13,30.58,28.00,27.16,25.56,25.17,24.86,24.17, 19.43,18.21,17.07,16.54,16.29,16.18,15.64。
Example 13
IIm: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylallylcarbamate;
the preparation method is the same as that of example 1; the yield was 59%.1H NMR(300MHz,CDCl3)δ6.25(s,1H),5.96– 5.76(m,1H),5.19(dd,J＝17.2,1.3Hz,1H),5.12(dd,J＝10.2,1.0Hz,1H),4.69(s,1H), 4.37(dd,J＝11.3,4.8Hz,1H),3.81(s,2H),3.53(td,J＝10.3,5.1Hz,1H),2.00–1.84(m, 2H),1.83–1.66(m,5H),1.64–1.35(m,11H),1.34–1.28(m,2H),1.26(s,4H),1.22(s, 4H),1.18(s,3H),1.11–1.01(m,2H),0.98(s,3H),0.92–0.85(m,9H),0.82(s,3H).13C NMR(125MHz,CDCl3)δ156.61,134.83,115.82,81.29,76.66,73.09,69.88,56.02,54.73, 51.21,49.84,49.20,43.42,39.83,38.60,38.10,37.04,36.46,35.76,34.84,33.02,31.13, 30.58,27.98,27.16,25.17,24.15,19.43,18.21,17.07,16.52,16.29,16.17,15.65。
Example 14
IIn: preparation of (3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R) -2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-ylpropylcarbamate;
the preparation method is the same as that of example 1; the yield was 61%.1H NMR(300MHz,CDCl3)δ6.27(s,1H),4.62(s, 1H),4.37(dd,J＝11.8,4.4Hz,1H),3.55(td,J＝10.3,5.1Hz,1H),3.15(s,2H),2.03–1.85 (m,2H),1.84–1.72(m,3H),1.70–1.41(m,15H),1.40–1.31(m,2H),1.28(s,4H),1.24(s, 4H),1.20(s,3H),1.13–1.03(m,2H),0.99(s,3H),0.97–0.86(m,12H),0.83(s,3H).13C NMR(125MHz,CDCl3)δ156.82,80.94,76.66,73.08,69.89,56.02,54.73,51.21,49.84, 49.20,42.66,39.82,38.61,38.10,37.04,36.46,35.75,34.84,33.02,31.13,30.58,27.98, 27.16,25.17,24.17,23.29,19.43,18.21,17.07,16.52,16.29,16.18,15.64,11.23。
Example 15
IIo preparation of O- ((3S, 8R, 10R, 12R, 14R) -12-hydroxy-4, 4,8,10, 14-pentamethyl-17- ((R-2,6, 6-trimethyltetrahydro-2H-pyran-2-yl) hexadecahydro-1H-cyclopenta [ a ] phenanthryl-3-yl) phenylthiocarbamate;
the preparation method is the same as that of example 1; the yield was 61%.1H NMR(300MHz,CDCl3)δ8.30(s,1H),7.33(t,J ＝7.2Hz,3H),7.18(d,J＝7.5Hz,2H),6.27(s,1H),5.20(dd,J＝11.7,4.2Hz,1H),3.54(td, J＝10.1,5.1Hz,1H),2.04–1.87(m,3H),1.84–1.70(m,4H),1.68–1.39(m,11H),1.27(s, 7H),1.22(s,3H),1.18(s,3H),1.15–1.09(m,1H),1.07–1.02(m,1H),0.98(s,3H),0.92(s, 6H),0.89(s,3H),0.85(s,3H).13C NMR(125MHz,CDCl3)δ188.89,136.93,128.98, 125.47,122.06,91.00,76.66,73.11,69.86,55.87,54.73,51.21,49.75,49.17,39.83,38.49, 37.08,36.46,35.76,34.78,33.04,31.13,30.58,29.70,27.92,27.15,25.19,23.29,19.43, 18.14,17.39,17.02,16.29,16.18,15.64。
Test example 1
In vitro anti-Abeta25-35Experimental test for neuroprotective effect of inducing PC12 cell injury
The influence of the target compound on the survival rate of PC12 cells was evaluated by using 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay. PC12 cells were cultured at 1X 105cells/mL were seeded at a density in complete medium in 96-well plates and incubated for 24 hours (100 μ L/well). Then, the administration group was added with the target compound at different concentrations (50. mu.L/well), and the remaining group was administered with 50. mu.L of the medium and cultured for another 4 hours. Subsequently, the administration group and the model group were administered with a β25-35(20. mu.M) and incubated for 24 hours. mu.L of MTT (5g/L, PBS buffer) was added to each well and the cells were further incubated for 4 hours. After removal of the supernatant, DMSO (150. mu.L/well) was added and shaken for 15 min. The optical density was measured at a wavelength of 570nm using a microplate reader (Thermo SCIENTIFIC, MA, USA).
TABLE 1 shows the inhibition of Abeta by panaxadiol derivatives25-35Protective effect of inducing PC12 cell damage:
note: results are expressed as mean ± standard deviation (n ═ 5).#P<0.05、##P<0.01 and###P<0.001 compared to blank;*P<0.05、**P<0.01 and***P<0.001 compared to the Α β -induced group.
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| CN114853839A (en) * | 2022-06-13 | 2022-08-05 | 延边大学 | A kind of panaxadiol compound and its preparation method and medical use |
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| CN111647036A (en) * | 2020-04-30 | 2020-09-11 | 烟台大学 | Ocotillol esterified derivatives, preparation method thereof and application thereof in preparing anti-inflammatory drugs |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114853839A (en) * | 2022-06-13 | 2022-08-05 | 延边大学 | A kind of panaxadiol compound and its preparation method and medical use |
| CN114853839B (en) * | 2022-06-13 | 2023-07-21 | 延边大学 | A kind of panaxadiol compound and its preparation method and medical application |
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