CN105968120A - Preparation method for tetrandrine and fangchinoline - Google Patents
Preparation method for tetrandrine and fangchinoline Download PDFInfo
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- CN105968120A CN105968120A CN201610366510.XA CN201610366510A CN105968120A CN 105968120 A CN105968120 A CN 105968120A CN 201610366510 A CN201610366510 A CN 201610366510A CN 105968120 A CN105968120 A CN 105968120A
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- tetrandrine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
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Abstract
The invention discloses a preparation method for tetrandrine and fangchinoline and belongs to the technical field of drug preparation. Lipotropy tertiary amine total alkali is adopted, and the preparation method comprises two steps that firstly, a medium pressure silica gel chromatography column method is used for separation, and elution is carried out through petroleum ether-ethyl acetate-diethylamine; secondly, purification is carried out through a preparation high performance liquid chromatography, methyl alcohol-water serves as a mobile phase, and finally, eluent is concentrated and evaporated to dryness. The method has the advantages that operation is convenient and quick and purity and the extraction rate are high.
Description
Technical field
The present invention relates to the preparation method of medicine, a kind of tetrandrine, the preparation method of B prime.
Background technology
Radix Stephaniae Tetrandrae calls Radix stephaniae tetrandrae, Stephania cepharatha Hayata, stone Bufo siccus, fall down to the ground arch, is the dried root of Menispermaceae stephania plant Radix Stephaniae Tetrandrae, and containing the Multiple components such as polysaccharide, alkaloid, its principle active component is tetrandrine and hanfangchin B.Tetrandrine has antiinflammatory, analgesia
, blood pressure lowering, antitumor, anti-hypoxia pulmonary hypertension, the suppression effect such as pulmonary fibrosis.Hanfangchin B is a kind of natural calcium antagonist, the diseases such as hypertension, diabetes, hepatic fibrosis is had therapeutical effect, also has brain cell protective effect and Broadspectrum antiphlogistic antibacterial action.Existing prepare tetrandrine, there is complex process in the method for B prime, it is high to become to produce cost, the common disadvantage that preparation efficiency is low.
Summary of the invention
It is an object of the invention to overcome the most methodical complex process and preparation cost high, it is provided that a kind of new tetrandrine, the preparation method of B prime.
For reaching above-mentioned purpose, the technical scheme of employing is:
A kind of tetrandrine, the preparation method of B prime, comprise the steps of:
1), silica gel medium pressure chromatogram column technique separation tetrandrine, B prime: filling a volume is the chromatographic column of 49mm × 460mm, being loaded in post by lipotropy tertiary amine total alkali, with petroleum ether-ethyl acetate-diethylamine eluting, flow velocity is 80 mL/min, collect eluent and inspect with TLC, merging same composition；Recycling design, obtains two kinds of components Fr 1 and Fr 2；
2) preparative high performance liquid chromatography purification tetrandrine, B prime: use YMC-pack chromatographic column 250*10 mmD for component Fr 1 and Fr 2, S-5 μm, 12 nm, selecting 230 nm for detection wavelength, flow velocity is 4 mL/min, and methanol-water is flowing phase, sample introduction separates, collect the eluent of two main peaks of isolated, eluent is concentrated respectively and is evaporated, to obtain final product.
Further, in described step 1), chromatographic column used silica gel is 300-400 mesh.
Further, in described step 1), the ratio of eluent petroleum ether-ethyl acetate-diethylamine is 9:1:0.1-5:1:0.1.
Further, in described step 1), rotation is used to steam instrument recycling design.
Further, described step 2) in, with 0.22 μm filtering with microporous membrane before component Fr 1 and Fr 2 sample introduction.
Further, described step 2) in, methanol, the ratio of water are 17:3.
Further, described step 2) in, sample size is 0.5 mL.
The silica gel medium pressure chromatogram column technique having the beneficial effect that the present invention using such scheme combines tetrandrine prepared by preparative high performance liquid chromatography, B prime possesses easy to operate, quick, the advantage that purity is high, a kind of preparation method can get two kinds of products, and extraction ratio is higher.
Accompanying drawing explanation
Fig. 1 is tetrandrine, the TLC bismuth potassium iodide of B prime and the TLC 254nm ultraviolet colour developing figure that the embodiment of the present invention is produced.
Fig. 2 is the tetrandrine that the embodiment of the present invention prepares 1The detection figure of H-NMR.
Fig. 3 is the hanfangchin B that the embodiment of the present invention prepares 1The detection figure of H-NMR.
Detailed description of the invention
It is further described the present invention below in conjunction with embodiment and accompanying drawing, but the present invention is not limited only to following embodiment, it is anticipated that those skilled in the art are in the case of combining prior art, and performance may produce many variations.
A kind of tetrandrine, the preparation method of B prime, comprise the steps of:
1), silica gel medium pressure chromatogram column technique separation tetrandrine, B prime: filling a volume is the chromatographic column of 49mm × 460mm, and chromatographic column used silica gel is 300-400 mesh.Being loaded in post by lipotropy tertiary amine total alkali, with petroleum ether-ethyl acetate-diethylamine (9:1:0.1-5:1:0.1) eluting, flow velocity is 80 mL/min, and the eluent TLC collected inspects, the merging that component is identical.Steam instrument recycling design with rotation, obtain two kinds of key components Fr 1 and Fr 2, distinguish the bigger tetrandrine of amount and B prime.
2), preparative high performance liquid chromatography purification tetrandrine, B prime: use YMC-pack chromatographic column (250*10
MmD, S-5 μm, 12 nm), select 230 nm for detection wavelength, flow velocity is 4 mL/min, and methanol (A)-water (B) is flowing phase, constantly adjusts methanol (A)-water (B) ratio and sample size (before sample introduction, 0.22 μm microporous filter membrane crossed by sample).Until groping a suitable chromatographic condition, finally showing that methanol, water ratio are 85%:15%, sample size is that 0.5 mL peak type is preferable, and separating degree is high.Collecting the eluent of two main peaks of isolated, remaining component discards.The eluent collected concentrates respectively and is evaporated, and takes TLC and standard control after appropriate product methanol dissolves, with petroleum ether: ethyl acetate: diethylamine (3:2:1) makees developing solvent, and developer made by bismuth potassium iodide.Inspect under 254nm ultraviolet.
Tetrandrine, B prime and its reference substance that the present invention prepares, spot colors and position consistency, composition is single.As it is shown in figure 1, left side is TLC bismuth potassium iodide colour developing figure, right side is Chinese TLC 254nm ultraviolet colour developing figure, and speckle is followed successively by tetrandrine, tetrandrine standard substance, hanfangchin B, hanfangchin B standard substance from left to right.
Such as Fig. 2, the tetrandrine produced1H-NMR result: off-white powder.1H-NMR(400 MHz, CDCl3):
2.33 (s, 3H), 2.41～2.47 (m, 1H), 2.52 (d,J=12.0 Hz, 1H), 2.62( s, 3H),
3.19(s, 3H), 3.25(dd, J =12.0,8.0 Hz, 1H),
3.37 (s, 3H), 3.43～3.48 (m, 1H), 3.51～3.56 (m, 1H), 3.75 (s, 3H), 3.88 (dd,J=12.0,4.0Hz, 1H), 3.93(s,3H), 5.99(s, 1H),
6.29(s, 1H), 6.30(m, 2H), 6.51(s,1H), 6.55(s, 1H), 6.81(d, J=8.0 Hz,
1H), 6.86(dd, J=8.0, 4.0 Hz, 1H), 6.87(s, 1H),
6.89(s, 1H), 7.13(dd, J=8.0, 4.0 Hz, 1H),
7.34(d, J=8.0 Hz, 1H) 。
Such as Fig. 3, the tetrandrine produced, off-white powder.
1H-NMR(400 MHz, CDCl3):
2.33 (s, 3H), 2.41～2.45 (m, 2H), 2.56 (d,J=16.0 Hz, 1H), 2.63( s, 3H),
3.26(dd, J =12.0,8.0 Hz, 1H), 3.35(s, 3H),
3.48～3.54 (m,
2H), 3.77(s, 3H), 3.88-3.91(m, 1H), 3.92(s,3H), 6.05(s, 1H), 6.29(s, 1H),
6.32(m, 1H), 6.52(s,1H), 6.56(s, 1H), 6.81(d, J=8.0 Hz, 1H), 6.86(o,
1H), 6.87(o, 1H), 6.89(o, 1H), 7.13(dd, J=8.0,
4.0 Hz, 1H), 7.34(d, J=8.0 Hz, 1H) 。
Tetrandrine is that the substituent group on No. 7 positions is different with the difference of B prime, and A prime is methoxyl group, and B prime is phenolic hydroxyl group.?1In H-NMR, between 3.0-4.0, there are 4 methoxyl group signals, 3.19 (s, 3H, H-7), 3.37 (s, 3H, H-6) 3.75 (s, 3H, H-6), 3.93 (s, 3H, H-12), and in hanfangchin B, only 3 methoxyl group signals 3.35 (s, 3H), 3.77 (s, 3H), 3.92 (s, 3H) it is 6 respectively, 6 and 12, so from1H-NMR can be easy to tell A prime and B prime.
Claims (7)
1. a preparation method for tetrandrine, B prime, its feature comprises the steps of:
1), silica gel medium pressure chromatogram column technique separation tetrandrine, B prime: filling a volume is the chromatographic column of 49mm × 460mm, is loaded in post by lipotropy tertiary amine total alkali, and with petroleum ether-ethyl acetate-diethylamine eluting, flow velocity is 80
ML/min, collects eluent and inspects with TLC, merges same composition；Recycling design, obtains two kinds of components Fr 1 and Fr 2；
2) preparative high performance liquid chromatography purification tetrandrine, B prime: use YMC-pack chromatographic column 250*10 mmD for component Fr 1 and Fr 2, S-5 μm, 12 nm, selecting 230 nm for detection wavelength, flow velocity is 4 mL/min, and methanol-water is flowing phase, sample introduction separates, collect the eluent of two main peaks of isolated, eluent is concentrated respectively and is evaporated, to obtain final product.
Preparation method the most according to claim 1, is characterized in that: in described step 1), and chromatographic column used silica gel is 300-400 mesh.
Preparation method the most according to claim 1, is characterized in that: in described step 1), and the ratio of eluent petroleum ether-ethyl acetate-diethylamine is 9:1:0.1-5:1:0.1.
Preparation method the most according to claim 1, is characterized in that: in described step 1), uses rotation to steam instrument recycling design.
Preparation method the most according to claim 1, is characterized in that: described step 2) in, with 0.22 μm filtering with microporous membrane before component Fr 1 and Fr 2 sample introduction.
Preparation method the most according to claim 1, is characterized in that: described step 2) in, methanol, the ratio of water are 17:3.
Preparation method the most according to claim 1, is characterized in that: described step 2) in, sample size is 0.5 mL.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111153909A (en) * | 2020-01-17 | 2020-05-15 | 石药集团江西金芙蓉药业股份有限公司 | A double-template molecular imprinting purification method for alpha-and beta-carotene in Stephania tetrandra |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850824A (en) * | 2006-04-27 | 2006-10-25 | 富力 | Benzene-free tetrandrine and its preparing method |
| CN101012229A (en) * | 2007-01-26 | 2007-08-08 | 北海阳光药业有限公司 | Hanfangchin A without benzene and chloroform and preparing method thereof |
| CN101033229A (en) * | 2007-02-09 | 2007-09-12 | 南开大学 | Separation of monosomic tetrandrine from tetrandrine total alkaloid by adsorption resin method |
| CN101288695A (en) * | 2007-04-16 | 2008-10-22 | 中国科学院成都生物研究所 | Preparation technique of alkaloids from Stephania tetrandra |
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2016
- 2016-05-30 CN CN201610366510.XA patent/CN105968120B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850824A (en) * | 2006-04-27 | 2006-10-25 | 富力 | Benzene-free tetrandrine and its preparing method |
| CN101012229A (en) * | 2007-01-26 | 2007-08-08 | 北海阳光药业有限公司 | Hanfangchin A without benzene and chloroform and preparing method thereof |
| CN101033229A (en) * | 2007-02-09 | 2007-09-12 | 南开大学 | Separation of monosomic tetrandrine from tetrandrine total alkaloid by adsorption resin method |
| CN101288695A (en) * | 2007-04-16 | 2008-10-22 | 中国科学院成都生物研究所 | Preparation technique of alkaloids from Stephania tetrandra |
Non-Patent Citations (2)
| Title |
|---|
| 徐应淑 等: "TLC法分离汉防己中汉防己甲素、乙素", 《遵义医学院学报》 * |
| 陶曙红等: "大孔吸附树脂在提取粉防己中汉防己甲素和汉防己乙素中的应用", 《时珍国医国药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111153909A (en) * | 2020-01-17 | 2020-05-15 | 石药集团江西金芙蓉药业股份有限公司 | A double-template molecular imprinting purification method for alpha-and beta-carotene in Stephania tetrandra |
| CN111153909B (en) * | 2020-01-17 | 2022-05-17 | 石药集团江西金芙蓉药业股份有限公司 | A double-template molecular imprinting purification method for alpha-and beta-carotene in Stephania tetrandra |
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