CN110680822A - 一种人参二醇、人参三醇的pcc氧化产物的应用 - Google Patents
一种人参二醇、人参三醇的pcc氧化产物的应用 Download PDFInfo
- Publication number
- CN110680822A CN110680822A CN201911119864.4A CN201911119864A CN110680822A CN 110680822 A CN110680822 A CN 110680822A CN 201911119864 A CN201911119864 A CN 201911119864A CN 110680822 A CN110680822 A CN 110680822A
- Authority
- CN
- China
- Prior art keywords
- panaxadiol
- panaxatriol
- pcc oxidation
- application
- oxidation product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- PVLHOJXLNBFHDX-XHJPDDKBSA-N Panaxadiol Chemical compound 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 17
- 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 title claims abstract description 17
- QFJUYMMIBFBOJY-UXZRXANASA-N Panaxatriol Chemical compound C[C@]1([C@H]2CC[C@@]3([C@@H]2[C@H](O)C[C@H]2[C@]3(C[C@@H](O)[C@H]3C(C)(C)[C@@H](O)CC[C@@]32C)C)C)CCCC(C)(C)O1 QFJUYMMIBFBOJY-UXZRXANASA-N 0.000 title claims abstract description 16
- VIXIMKLMEZTTTC-UHFFFAOYSA-N Panaxatriol Natural products CC1(C)CCCC(O1)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5C(O)CC34C VIXIMKLMEZTTTC-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 230000003647 oxidation Effects 0.000 title claims abstract description 14
- 238000007254 oxidation reaction Methods 0.000 title claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 21
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 11
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 8
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims description 13
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims description 5
- 235000003140 Panax quinquefolius Nutrition 0.000 claims description 5
- 235000008434 ginseng Nutrition 0.000 claims description 5
- 150000002009 diols Chemical class 0.000 claims description 3
- 241000208340 Araliaceae Species 0.000 claims 4
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 17
- 239000002994 raw material Substances 0.000 abstract description 7
- 229930189092 Notoginsenoside Natural products 0.000 abstract description 6
- 231100000053 low toxicity Toxicity 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 11
- 210000001841 basilar artery Anatomy 0.000 description 8
- 210000004351 coronary vessel Anatomy 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 208000006906 Vascular Ring Diseases 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000012224 working solution Substances 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 241000180649 Panax notoginseng Species 0.000 description 5
- 235000003143 Panax notoginseng Nutrition 0.000 description 5
- 244000131316 Panax pseudoginseng Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 235000003181 Panax pseudoginseng Nutrition 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 3
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002040 relaxant effect Effects 0.000 description 3
- 239000009692 xuesetong Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- 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 description 2
- 235000002791 Panax Nutrition 0.000 description 2
- 241000208343 Panax Species 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000036316 preload Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 235000017709 saponins Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 244000061458 Solanum melongena Species 0.000 description 1
- 235000002597 Solanum melongena Nutrition 0.000 description 1
- 229940122119 Thromboxane receptor agonist Drugs 0.000 description 1
- -1 Xuesaitong) Natural products 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003767 thromboxane receptor stimulating agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种人参二醇、人参三醇的PCC氧化产物的应用;用于治疗心脑血管疾病,本发明有益效果是从三七皂苷为原材料制备获取的PCC氧化产物,用于生产一种毒性小、活性强、生物利用度高的用于治疗心脑血管疾病的药品。
Description
技术领域
本发明涉及心血管医药领域,尤其涉及是一种人参二醇、人参三醇的PCC氧化产物的应用。
背景技术
三七是主产云南的国际瞩目的明星药用植物,现有含三七的产品,多使用三七总皂苷(比如血塞通),或使用三七提取物,甚至直接使用三七粉,科技含量不高、附加值低。其中,血塞通(三七总皂苷)已成为预防和治疗心脑血管疾病的基础药物。药物代谢动力学研究表明血塞通可以在体内发生代谢,典型代谢为脱糖至生成苷元,这表明其发生疗效的主要成分为苷元或苷元衍生物,根据C-6位上是否连有羟基,将三七皂苷分为人参二醇型皂苷和人参三醇型皂苷。有望制成毒性小,活性强,生物利用度高的治疗心脑血管疾病药物,并且将促进三七作用机制的阐明,有望提高三七的产品附加值。
发明内容
本发明的目的在于提供一种人参二醇、人参三醇的PCC氧化产物的应用,以提高三七皂苷为原料生成的衍生物工业获得一种毒性小,活性强,生物利用度高的治疗心脑血管疾病的药品。
为实现上述目的,本发明提供如下技术方案:
一种人参二醇、人参三醇的PCC氧化产物的应用,治疗心脑血管疾病药物的应用。
进一步地,药物浓度为0.1—1000μmol/L。
进一步地,最佳浓度为8umol/L。
本发明的技术效果和优点:
(1)毒性小,活性强,生物利用度高的治疗心脑血管疾病药物。
(2)三七的原料成本较低,可提高三七的产品附加值,原材料获取较为容易。
(3)通过三七皂苷的降解制备人参二醇和人参三醇,并进一步采用PCC氧化法制备人参二醇和人参三醇衍生物后均具有舒张心脑血管的活性。
附图说明
图1为本发明提供的化合物1-5结构式。
图2为本发明提供的BA血管累积量效曲线。
图3为本发明提供的CA血管累积量效曲线。
具体实施方式
下面将结合本发明实施例中的具体应用,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例
本实施例进一步地结合试验数据及案例试验证明,化合物的用于心血管治疗的药理特性,由三七制备的衍生物的化学结构式如图1所示,
人参二醇和人参三醇的制备
称取三七总皂苷100g,置于1000ml的圆底烧瓶中,加入36.5%浓盐酸500ml,室温条件下搅拌24小时,抽滤得到粗产物45g。固体粗产物用100-200目硅胶1:1拌样上样,经200-300目硅胶分离,依次用石油醚-乙酸乙酯(10:1→10:3)梯度洗脱,薄层色谱(TCL)检测,依次得到化合物1(4.25g)和化合物2(2.5g)。
化合物1
白色粉末,C30H52O3,
1HNMR(CDCl3,500MHz)δppm:3.52(1H,d,H-12),3.19(1H,s,H-3),1.24(3H,s,H-26),1.21(3H,s,H-28),1.18(3H,s,H-21),0.97(3H,s,H-29),0.97(3H,s,H-18),0.87(3H,s,H-19),0.77(3H,s,H-30);
13CNMR(CDCl3,125MHz)δppm:78.93(C-3),76.67(C-20),73.10(C-25),69.94(C-12),55.87(C-5),54.74(C-17),51.24(C-14),49.93(C-9),49.16(C-13),39.79(C-8),38.93(C-1),38.87(C-4),37.13(C-10),36.46(C-24),35.76(C-22),34.88(C-7),33.05(C-26),31.16(C-15),30.57(C-11),28.05(C-28),27.49(C-2),27.12(C-27),25.19(C-16),19.42(C-21),18.32(C-6),17.07(C-30),16.29(C-23),16.14(C-19),15.63(C-18),15.37(C-29).
化合物2
白色粉末,C30H52O4,
1HNMR(CDCl3,500MHz)δppm:3.52(1H,d,H-12),1.25(3H,s,H-27),1.22(3H,s,H-26),1.18(3H,s,H-21),1.17(3H,s,H-28),1.06(3H,s,H-18),0.97(3H,s,H-29),0.92(3H,s,H-19),0.89(3H,s,H-30);
13CNMR(CDCl3,125MHz)δppm:78.61(C-3),76.64(C-20),73.18(C-25),69.82(C-12),68.77(C-6),61.14(C-5),54.66(C-17),51.04(C-14),49.39(C-9),48.74(C-13),47.07(C-7),41.00(C-8),39.26(C-4),39.18(C-10),38.67(C-1),36.42(C-24),35.71(C-22),33.03(C-26),31.12(C-15),30.87(C-28),30.37(C-11),27.13(C-27),27.07(C-2),25.14(C-16),19.39(C-21),17.18(C-30),17.16(C-19),17.03(C-18),16.25(C-23),15.50(C-29).
称取1g化合物1置于10ml茄型烧瓶中,加入2mol/LKOH甲醇溶液50ml,于90℃加热回流2小时,硅胶TCL检测至原料点消失停止反应,冷却至室温。用2mol/LHCL溶液中和至中性,减压蒸干,加入20ml水后用氯仿萃取三次(50ml×3),合并有机相得到固体860mg。经硅胶柱色谱纯化,石油醚-乙酸乙酯(19:1-17:3)梯度洗脱得到化合物3,产率86.3%。
化合物3
白色粉末,C30H48O4,
1HNMR(CDCl3,500MHz)δppm:3.64(1H,s,H-12),1.27(3H,s,H-27),1.22(3H,s,H-26),1.18(3H,s,H-21),1.18(3H,s,H-28),1.10(3H,s,H-18),1.04(3H,s,H-29),0.96(3H,s,H-19),0.83(3H,s,H-30);
13CNMR(CDCl3,125MHz)δppm:214.54(C-3),211.01(C-6),76.57(C-20),73.32(C-25),69.21(C-12),65.36(C-5),54.81(C-17),52.46(C-7),51.01(C-14),49.82(C-9),48.94(C-13),46.98(C-8),46.18(C-10),43.39(C-4),41.18(C-1),36.39(C-24),35.65(C-22),33.92(C-2),33.02(C-26),31.12(C-15),30.94(C-11),27.12(C-27),24.83(C-16),21.62(C-28),19.40(C-21),17.25(C-30),16.41(C-19),16.22(C-18),15.76(C-23),14.15(C-29).
人参二醇PCC氧化产物的制备
将100g三氧化铬迅速加入到184ml,6molL-1盐酸中并不断搅拌,5min后将均相体系冷却至0℃,在至少10min内小心加入79.1mg吡啶。将反应体系重新冷却至0℃,得橙黄色固体,过滤,真空干燥lh,得PCC180g。
称取人参二醇(500mg,1eq,1.09mmol)加入到50ml二颈瓶中,先加入15mlCH2Cl2充分溶解后,再称取PCC(3eq,701.77mg),15mlCH2Cl2充分溶解搅拌均匀后,在搅拌的情况下快速加入到二颈瓶中,用TLC板跟踪反应过程,反应2小时后,TLC跟踪反应过程,原料消失后停止反应,用100-200目硅胶快速过滤,溶剂用乙酸乙酯冲洗,乙酸乙酯减压浓缩后,柱色谱纯化得化合物4。
化合物4
白色粉末,
1HNMR(500MHz,CDCl3)δ:0.86(3H,s,H-19),0.97(3H,s,H-30),1.00(3H,s,H-28),1.02(3H,s,H-18),1.06(3H,s,H-29),1.18(3H,s,H-26),1.21(3H,s,H-27),1.26(3H,s,H-21),3.52-3.57(1H,m,CH-12);
13CNMR(CDCl3,125MHz)δ:217.9(C-3),76.6(C-20),73.3(C-25),69.9(C-12),55.2(C-17),54.5(C-13),51.1(C-14),49.2(C-9),49.1(C-5),47.3(C-4),39.6(C-1),39.6(C-8),36.7(C-10),36.3(C-24),35.6(C-2),34.1(C-22),34.0(C-7),33.0(C-27),31.0(C-15),30.7(C-11),27.0(C-26),26.6(C-29),25.0(C-16),20.9(C-28),19.6(C-6),19.3(C-21),16.8(C-30),16.1(C-23),15.9(C-18),15.2(C-19).
人参三醇PCC氧化产物
将100g三氧化铬迅速加入到184ml,6molL-1盐酸中并不断搅拌,5min后将均相体系冷却至0℃,在至少10min内小心加入79.1mg吡啶。将反应体系重新冷却至0℃,得橙黄色固体,过滤,真空干燥lh,得PCC180g。
称取人参三醇(500mg,1eq,1.09mmol)加入到50ml二颈瓶中,先加入15mlCH2Cl2充分溶解后,再称取PCC(3eq,701.77mg),15mlCH2Cl2充分溶解搅拌均匀后,在搅拌的情况下快速加入到二颈瓶中,用TLC板跟踪反应过程,反应2小时后,TLC跟踪反应过程,原料消失后停止反应,用100-200目硅胶快速过滤,溶剂用乙酸乙酯冲洗,乙酸乙酯减压浓缩后,柱色谱纯化得化合物5。
化合物5
白色粉末,
1HNMR(500MHz,CDCl3)δ:0.97(3H,s);1.02(3H,s);1.16(3H,s);1.08(3H,s);1.16(3H,s);1.23(3H,s);1.25(3H,s);1.46(3H,s);2.55(2H,d,H-7);3.61(1H,m,H-12);6.40(1H,br.s,-OH);
13CNMR(CDCl3,125MHz)δ:41.97(t,C-1),34.72(t,C-2),215.37(s,C-3),44.20(s,C-4),66.14(d,C-5),211.85(s,C-6),53.27(t,C-7),47.78(s,C-8),49.73(d,C-9),46.98(s,C-10),31.93(t,C-11),70.02(d,C-12),50.61(d,C-13),51.82(s,C-14),31.73(t,C-15),25.64(t,C-16),55.60(d,C-17),17.23(q,C-18),16.56(q,C-19),78.20(s,C-20),20.21(q,C-21),36.45(t,C-22),17.03(t,C-23),37.19(t,C-24),74.13(s,C-25),33.84(q,C-26),27.93(q,C-27),22.43(q,C-28),24.97(q,C-29),18.05(q,C-30)。
PCC氧化物的试剂及药物的配制
血栓素受体激动剂U46619:分子量为350.5,真空条件下使U46619中的溶剂乙酸乙酯溶液挥干,再用无水乙醇溶解U46619得母液(2mM),-20℃保存.临用前用三蒸水稀释至所需浓度。
将受试药物设成摩尔浓度:0.1μmol/L,0.3μmol/L,1μmol/L,3μmol/L,10μmol/L,30μmol/L,100μmol/L,300μmol/L和1000μmol/L的剂量组,利用累积浓度加入法进行活性检测,具体配制加入方法见下表1。
表1受试样品摩尔浓度配制表
MOPS-PSS缓冲液含(1L):NaCl81.8g,KCl3.5g,MOPS4.2g,Na2HPO4.12H2O4.3g,Na2-EDTA.2H2O0.07g,MgSO4.7H2O12.3g,CaCl25.5g,Glucose.H2O1.1g.
MOPS-KPSS缓冲液含(1L):NaCl49.5g,KCl44.8g,MOPS4.2g,Na2HPO4.12H2O4.3g,Na2-EDTA.2H2O0.07g,MgSO4.7H2O12.3g,CaCl25.5g,Glucose.H2O1.1g.
药理实验过程
血管环制备与平衡
大鼠用10%的乌拉坦(10mL/kg)麻醉致死,并迅速取出心脏和大脑置于4℃MOPS-PSS液中.体式解剖显微镜下,用显微手术器械将心右冠状动脉(CA)和脑基底动脉(BA)取出并且将周围组织分离干净,CA和BA剪成长度约1mm血管环备用。
体式解剖显微镜下,用2根长1.5cm,直径60um的钨丝穿过血管环(注意尽量不要损伤血管内皮等),分别挂置于DMT浴槽中,浴槽中盛MOPS-PSS工作液,恒温37℃并且持续通入O2。
待血管环全部置于DMT上后,调节微调装置,分别给CA和BA约1mN、1.5mN的预负荷。
每隔20min换1次MOPS-PSS(37℃)工作液,每次5ml,平衡三次后,然后更换MOPS-KPSS工作液(含60mMK+)5mL检测血管环活性,检测两次,每次5min。当收缩力为预负荷2倍左右时认为活性合格,用MOPS-PSS(37℃)工作液洗涤2-3次后再加入5mLMOPS-PSS(37℃)工作液平衡后用于实验。然后按照预先计算的给药体积加药。
CA、BA平衡并检测血管环活性合格后,加入U46619收缩血管,待收缩达到最大值且平衡后,每隔10min累积加入配置好的药物。同一药物的不同剂量在同一根血管环上检测并用PowerLAB数据记录和分析***采集数据。每一个受试药物取8根血管环进行重复试验。
统计学数据处理分析
采用SigmaStat10.0统计分析软件对数据进行分析处理,采用SigmaPlot利用均值和标准误作图表示各个受试药物对CA和BA的舒张作用的影响;并模拟计算半数有效浓度(EC50),相对张力值计算公式为:相对张力值=(X-平衡值)/(U4收缩值-平衡值)×100%。
以下各图表示累积量效曲线图2-3所示,
横坐标表示受试药物浓度,
纵坐标表示受试药物对血管的相对张力值,
相对张力值越小表示药物对血管的舒张活性越好,相对张力值小于50%时,认为有一定程度的血管舒张活性。
表2受试样品舒张大鼠CA/BA的EC50
结论总结
人参二醇和人参三醇及其PCC氧化产物均具有舒张SD大鼠心脑血管的作用,在舒张BA、CA活性中,人参三醇的EC50值(15.65umol/L、5.59umol/L)最低,均低于人参二醇,并且在舒张BA活性中,人参三醇PCC产物的EC50值低于人参二醇,都在8umol/L左右,数值相对稳定。
最后应说明的是:以上所述仅为本发明的优选实施例而已,并不用于限制本发明,尽管参照前述实施例对本发明进行了详细的说明,对于本领域的技术人员来说,其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (3)
1.一种人参二醇、人参三醇的PCC氧化产物的应用,其特征在于:治疗心脑血管疾病药物的应用。
2.根据权利要求1所述的一种人参二醇、人参三醇的PCC氧化产物的应用,其特征在于:药物浓度为0.1—1000μmol/L。
3.根据权利要求2所述的一种人参二醇、人参三醇的PCC氧化产物的应用,其特征在于:药物浓度为8umol/L。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911119864.4A CN110680822A (zh) | 2019-11-15 | 2019-11-15 | 一种人参二醇、人参三醇的pcc氧化产物的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911119864.4A CN110680822A (zh) | 2019-11-15 | 2019-11-15 | 一种人参二醇、人参三醇的pcc氧化产物的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110680822A true CN110680822A (zh) | 2020-01-14 |
Family
ID=69116854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911119864.4A Pending CN110680822A (zh) | 2019-11-15 | 2019-11-15 | 一种人参二醇、人参三醇的pcc氧化产物的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110680822A (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1545382A (zh) * | 2002-01-05 | 2004-11-10 | LOTTE�ƹ���ʽ���� | 加工人参的方法和加工过的人参提取物的用途 |
CN1634098A (zh) * | 2004-11-18 | 2005-07-06 | 张平 | 达玛烷型皂苷人参低元醇衍生物的用途及其制剂 |
CN101428050A (zh) * | 2008-12-15 | 2009-05-13 | 云南白药集团股份有限公司 | 一种用于治疗血栓、心脑血管***疾病的活性组合物 |
CN101653447A (zh) * | 2009-07-14 | 2010-02-24 | 澳门大学 | 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 |
CN102924556A (zh) * | 2012-11-05 | 2013-02-13 | 烟台大学 | 具有抗菌活性的(20S,24R)-ocotillol型人参皂苷类衍生物、其制备方法及用途 |
CN103709223A (zh) * | 2012-10-09 | 2014-04-09 | 中国科学院昆明植物研究所 | 达玛烷三萜衍生物及其药物组合物和其在制药中的应用 |
CN105367619A (zh) * | 2015-11-13 | 2016-03-02 | 昆明医科大学 | 3-去氧-3-氨基-人参二醇及其制备方法和应用 |
-
2019
- 2019-11-15 CN CN201911119864.4A patent/CN110680822A/zh active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1545382A (zh) * | 2002-01-05 | 2004-11-10 | LOTTE�ƹ���ʽ���� | 加工人参的方法和加工过的人参提取物的用途 |
CN1634098A (zh) * | 2004-11-18 | 2005-07-06 | 张平 | 达玛烷型皂苷人参低元醇衍生物的用途及其制剂 |
CN101428050A (zh) * | 2008-12-15 | 2009-05-13 | 云南白药集团股份有限公司 | 一种用于治疗血栓、心脑血管***疾病的活性组合物 |
CN101653447A (zh) * | 2009-07-14 | 2010-02-24 | 澳门大学 | 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 |
CN103709223A (zh) * | 2012-10-09 | 2014-04-09 | 中国科学院昆明植物研究所 | 达玛烷三萜衍生物及其药物组合物和其在制药中的应用 |
CN102924556A (zh) * | 2012-11-05 | 2013-02-13 | 烟台大学 | 具有抗菌活性的(20S,24R)-ocotillol型人参皂苷类衍生物、其制备方法及用途 |
CN105367619A (zh) * | 2015-11-13 | 2016-03-02 | 昆明医科大学 | 3-去氧-3-氨基-人参二醇及其制备方法和应用 |
Non-Patent Citations (6)
Title |
---|
QIONG WU,等: "Synthesis and evaluation of panaxatriol derivatives as Na+, K+-ATPase inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
周金娜: "三七皂苷与类似物结构改造及舒张心脑血管活性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
曹青青,等: "人参二醇和人参三醇氧化反应的研究", 《云南中医学院学报》 * |
李冠烈: "三七的现代研究与进展(二)", 《世界中西医结合杂志》 * |
赵一纯,等: "人参二醇与人参三醇衍生物的氧化及细胞毒活性", 《昆明医科大学学报》 * |
郭巍怡,等: "三七皂苷元的乙酰化结构修饰及活性研究", 《云南中医学院学报》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Yang et al. | Baimantuoluosides DG, four new withanolide glucosides from the flower of Datura metel L. | |
CN110028547B (zh) | 一种薯蓣皂苷元3-oh衍生物及其制备方法和医药用途 | |
CN110903340B (zh) | 四环三萜衍生物及其药物组合物和应用 | |
CN112300242B (zh) | 一种呋甾皂苷类化合物单体的制备方法 | |
Kikuchi et al. | Strophasterols E and F: Rearranged ergostane-type sterols from Pleurotus eryngii | |
CN106496171B (zh) | 具有抗肿瘤活性的多环多异戊烯基间苯三酚类化合物、其制备方法及应用 | |
Xu et al. | Chemical synthesis of saponins: An update | |
CN112125944A (zh) | 无柄灵芝中具有α葡萄糖苷酶抑制活性的三萜化合物的制备方法及应用 | |
CN110680822A (zh) | 一种人参二醇、人参三醇的pcc氧化产物的应用 | |
CN110092809B (zh) | 一种利用巨大芽孢杆菌分离提取β-谷甾醇的方法 | |
CN102391352B (zh) | 救必应酸氨基酸衍生物及其在制备抗肿瘤的药物中的应用 | |
CN108250263B (zh) | 三七中三种具有抗肿瘤活性的化合物、制备方法和药物用途 | |
CN102659904B (zh) | 一种常春藤皂苷元及其盐的制备方法 | |
CN113072609B (zh) | 三萜类化合物及其制备方法和用途 | |
Fernández-Herrera et al. | Side-chain opening of steroidal sapogenins to form 22-oxocholestanic skeletons: An approach to analogues of the aglycone of the potent anticancer agent OSW-1 | |
SATO et al. | Chemistry of the Spiroaminoketal Side Chain of Solasodine and Tomatidine. VI. 1 The Beckmann Rearrangement of the Oximino Derivatives | |
CN109705189B (zh) | 具有式i所示结构的三萜衍生物及其制备方法和应用 | |
CN101077852A (zh) | 参麦注射液的化学成分的制备及其在治疗心脑血管疾病中的应用 | |
Yang et al. | Synthesis and crystal structures of two C24 epimeric 3-acetyled 20 (R)-ocotillol type sapogenins obtained from 20 (R)-protopanaxadiol | |
Zong et al. | Total synthesis of ipomoeassin F and its analogs for biomedical research | |
CN114380880B (zh) | Fmoc-氨基酸修饰的20(S)-原人参二醇衍生物及制备方法和用途 | |
CN116693591B (zh) | 一个乌苏烷三萜咖啡酸酯化合物的制备与抗肿瘤应用 | |
CN105732756B (zh) | 一种脂溶性***衍生物的纯化方法 | |
Gnabre et al. | Characterization of steroidal glycosides from Tylophora sylvatica | |
CN114349722B (zh) | 一种强心苷化合物及其制备方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200114 |
|
RJ01 | Rejection of invention patent application after publication |