CN108863741A - A kind of synthetic method of hypericin - Google Patents
A kind of synthetic method of hypericin Download PDFInfo
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- CN108863741A CN108863741A CN201710329839.3A CN201710329839A CN108863741A CN 108863741 A CN108863741 A CN 108863741A CN 201710329839 A CN201710329839 A CN 201710329839A CN 108863741 A CN108863741 A CN 108863741A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
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Abstract
The invention discloses a kind of synthetic methods of hypericin, JSTS-1 is dissolved in acetic acid, stannous chloride is added dropwise, it is heated to reflux, it is cooled to room temperature, filter drying, it is dissolved in the in the mixed solvent of pyridine and piperidines, green vitriol pyridine nitric oxide is added, replace nitrogen protection, it is protected from light heating reaction, cooling decompression is spin-dried for, dilute hydrochloric acid is added to stir, it filters, filter cake is washed to neutrality, filter cake is dissolved in methanol, add silica gel, decompression is spin-dried for, column chromatography for separation, product adding into acetone, low temperature and irradiance, vacuum is spin-dried for, methanol is added to be stirred heating, then active carbon is added to be stirred, it filters, mother liquor is spin-dried for, it adds water and stirs, it filters, it is washed to mother liquor clarification, solid scrapes, methylene chloride stirring is added, it filters, methylene chloride is washed till mother liquor clarification, solid is dry, obtain target product.Synthetic method of the invention, synthetic route is simple, and purifying difficulty is low, and total recovery is more than 60%, is suitble to industrialization.
Description
Technical field
The present invention relates to the field of chemical synthesis, the synthetic method of specifically a kind of hypericin.
Background technique
Leaf Fructus Forsythiae confirms its safety and effectiveness by the application and a large amount of clinical trial in several centuries, causes doctor
The attention of medicine circle, it is growing day by day to its demand.In terms of European applicable cases, existing antidepression preparation has external preparation again,
Dosage is all very big, and whole world patient needs dose very big up to 100,000,000 people according to statistics.It can be seen that undeveloped domestic and global city
Field has a high potential, and is worth furtheing investigate and simultaneously pushes to market.Also, AIDS is spread unchecked in the world, and treatment method and drug are not
More, the U.S. once developed a small amount of drug, but created a monopoly.China researcher can further investigate in this regard, utilize spun gold
Peach element can inhibit the active characteristic of human immunodeficiency virus's reverse transcriptase, develops anti-AIDS new drug, benefits for the mankind.
Based on hypericin in the functions such as antiviral and antitumor, treatment depression, enhancing be immune, makes hypericum perforatum pharmaceutically and have and is non-
Often wide development prospect.
The research of the external extracting method in relation to hypericin is to start to carry out in the age, and hypericum perforatum grinds in the country
In terms of studying carefully the pharmacology for being concentrated mainly on hypericin, and the later of progress is studied to hypericin extraction separation method, until
Age Mo in last century just has been reported that.Currently, the method for domestic current largely rests in the extracting method of hypericin, and it is right
Its separate, purifying technique study it is less.And annual output and the market demand are extremely uneven.
Hypericin is produced with three step chemical synthesis now, compensates for insufficient supply in the market.
Summary of the invention
The purpose of the present invention is to provide a kind of synthetic methods of hypericin, mentioned above in the background art to solve
Problem.
To achieve the above object, the present invention provides the following technical solutions：
A kind of synthetic method of hypericin, specific step is as follows：
(1) JSTS-1 is dissolved in the acetic acid of 48~52 times of volumes, stannous chloride is added dropwise, temperature is not higher than 130 when dropwise addition
DEG C, flow back 2.8~3.2h at 118~122 DEG C, is cooled to room temperature, and solid is precipitated, and filters drying, obtains yellow solid JSTS-
2,
(2) JSTS-2 is dissolved in the in the mixed solvent of 18~22 times of volume pyridines and 1.8~2.2 times of volumes piperidines, is added
Green vitriol pyridine nitric oxide replaces nitrogen protection, is heated to reacting 1.4 at 112~118 DEG C under the conditions of being protected from light
~1.6h, cooling decompression are spin-dried for, and the 3wt% dilute hydrochloric acid of 180~220 times of volumes is then added, stirs 25~35min, filters,
Filter cake is washed with water to neutrality, and filter cake is dissolved in methanol, and silica gel is added, and decompression is spin-dried for, and column chromatography for separation obtains atropurpureus solid
JSTS-3；
(3) JSTS-3 is added in the acetone of 90~110 times of volumes, 110~130h of 400W illumination, vacuum at 0~10 DEG C
It is spin-dried for, the methanol of 45~55 times of volumes is added, is heated with stirring to 58~62 DEG C, active carbon is then added, is stirred at 58~62 DEG C
28~32min is filtered, and mother liquor is spin-dried for, and the water that 45~55 times of volumes are added stirs 28~32min, filters, it is clear to be washed to mother liquor
Clearly, solid scrapes, and the methylene chloride of 48~52 times of weight is added, and stirs 28~32min, filters, it is clear that methylene chloride is washed till mother liquor
Clearly, solid is dry, obtains the target product of reddish black solid.
As a further solution of the present invention：In the step (1), stannous chloride is dissolved in the hydrochloric acid that mass fraction is 15%
In solution.
As a further solution of the present invention：In the step (1), during the dropwise addition of stannous chloride, the temperature of mixed liquor
Degree is not higher than 130 DEG C.
As further scheme of the invention：In the step (2), the mass fraction of dilute hydrochloric acid is 2.5~3.5%.
Compared with prior art, the beneficial effects of the invention are as follows：
Synthetic method of the invention, synthetic route is simple, and purifying difficulty is low, and total recovery is more than 60%, is suitble to industrialization.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical scheme in the embodiment of the invention is clearly and completely described,
Obviously, described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
Steps are as follows for the synthetic method of hypericin：
(1) JSTS-1 is dissolved in the acetic acid of 50 times of volumes, stannous chloride is added dropwise and (is dissolved in the hydrochloric acid that mass fraction is 15%
In solution), temperature is not higher than 130 DEG C when dropwise addition, and 120 DEG C of reflux 3h are cooled to room temperature, and solid is precipitated, and filters and is dried to obtain Huang
Color solid jsts-2, route is as follows,
(2) JSTS-2 is dissolved in the in the mixed solvent of 20 times of volume pyridines and 2 times of volumes piperidines, it is sub- that seven hydrated sulfuric acids are added
Iron pyridine nitric oxide replaces nitrogen protection, and 115 DEG C of reaction 1.5h are heated under the conditions of being protected from light, and cooling decompression is spin-dried for (sample
Bottle pays attention to being protected from light), 3% dilute hydrochloric acid of 200 times of volumes is added, stirs 30min, filters, filter cake is washed with water to neutrality, and filter cake is dissolved in
In methanol, silica gel is added, decompression is spin-dried for, column chromatography for separation (dcm-dcm-dcm：Ea=dcm-1:1-ea), it is black to obtain 5.9g purple
Color solid, purity 43%, route is as follows；
It has used the Piperidine of catalytic amount that the reaction time is greatly saved from JSTS-2 to JSTS-3, and has improved
Conversion ratio indirectly produces help to JSTS-3 to JSTS-4 conversion ratio so that means of purification is more easier；
(3) JSts-3 is added in the acetone of 100 times of volumes, 400W illumination 120h, T vacuum is spin-dried at 0~10 DEG C, is added
The methanol of 50 times of volumes is heated with stirring to 60 DEG C, and active carbon is added, stirs 30min at 60 DEG C, filters, and mother liquor is spin-dried for, and is added 50
The water of times volume stirs 30min, filters, and is washed to mother liquor clarification, and solid scrapes, and 50 times of methylene chloride (DCM) are added, and stirs
30min is filtered, and methylene chloride (DCM) is washed till mother liquor clarification, and solid is dry, obtains the target product of reddish black solid, route is such as
Under,
Whole synthetic route of the invention is as follows：
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.
Claims (4)
1. a kind of synthetic method of hypericin, which is characterized in that specific step is as follows：
(1) JSTS-1 is dissolved in the acetic acid of 48~52 times of volumes, stannous chloride is added dropwise, then flows back at 118~122 DEG C
2.8~3.2h is cooled to room temperature, and solid is precipitated, and is filtered drying, is obtained yellow solid JSTS-2,
(2) JSTS-2 is dissolved in the in the mixed solvent of 18~22 times of volume pyridines and 1.8~2.2 times of volumes piperidines, seven water are added
Close ferrous sulfate pyridine nitric oxide, replace nitrogen protection, be heated under the conditions of being protected from light at 112~118 DEG C reaction 1.4~
1.6h, cooling decompression are spin-dried for, and the 3wt% dilute hydrochloric acid of 180~220 times of volumes is then added, stirs 25~35min, filters, filter cake
It is washed with water to neutrality, filter cake is dissolved in methanol, and silica gel is added, and decompression is spin-dried for, and column chromatography for separation obtains atropurpureus solid JSTS-
3；
(3) JSTS-3 being added in the acetone of 90~110 times of volumes, 110~130h of 400W illumination, vacuum are spin-dried at 0~10 DEG C,
The methanol of 45~55 times of volumes is added, is heated with stirring to 58~62 DEG C, is then added active carbon, stirring 28 at 58~62 DEG C~
32min is filtered, and mother liquor is spin-dried for, and the water that 45~55 times of volumes are added stirs 28~32min, filters, and is washed to mother liquor clarification, Gu
Body scrapes, and the methylene chloride of 48~52 times of weight is added, and stirs 28~32min, filters, and methylene chloride is washed till mother liquor clarification, Gu
Soma is dry, obtains the target product of reddish black solid.
2. the synthetic method of hypericin according to claim 1, which is characterized in that in the step (1), stannous chloride
It is dissolved in the hydrochloric acid solution that mass fraction is 15%.
3. the synthetic method of hypericin according to claim 1, which is characterized in that in the step (1), stannous chloride
Dropwise addition during, the temperature of mixed liquor is not higher than 130 DEG C.
4. the synthetic method of hypericin according to claim 1, which is characterized in that in the step (2), dilute hydrochloric acid
Mass fraction is 2.5~3.5%.(specific name of JSTS-1, JSTS-2, JSTS-3, JSTS-4 please be provided).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111138262A (en) * | 2020-01-13 | 2020-05-12 | 成都金石缘科技有限公司 | Hypericin synthesis method |
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|---|---|---|---|---|
| CN1827574A (en) * | 2006-04-19 | 2006-09-06 | 中国农业科学院兰州畜牧与兽药研究所 | Chemical synthesis process for hypericin and derivatives thereof |
| WO2011034922A1 (en) * | 2009-09-15 | 2011-03-24 | Hy Biopharma, Inc. | Methods for preparing hypericin |
| CN102126942A (en) * | 2010-12-22 | 2011-07-20 | 湖北工业大学 | Method for synthesizing hypericin |
| CN102180782A (en) * | 2011-03-23 | 2011-09-14 | 中国农业科学院兰州畜牧与兽药研究所 | Method for synthesizing hypericin |
| WO2012081022A1 (en) * | 2010-12-16 | 2012-06-21 | Sensit Science Ltd. | Anthraquinones for use as radiosensitizers in cancer treatment |
| CN103274920A (en) * | 2013-06-14 | 2013-09-04 | 西北农林科技大学 | Efficient hypericin synthesizing method initiated by monochromatic light |
| CN104193610A (en) * | 2014-08-05 | 2014-12-10 | 中南大学 | Synthesis method of hypericin |
| CN106588622A (en) * | 2016-12-16 | 2017-04-26 | 陕西嘉禾药业有限公司 | Hypericin synthesis method |
-
2017
- 2017-05-11 CN CN201710329839.3A patent/CN108863741A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1827574A (en) * | 2006-04-19 | 2006-09-06 | 中国农业科学院兰州畜牧与兽药研究所 | Chemical synthesis process for hypericin and derivatives thereof |
| WO2011034922A1 (en) * | 2009-09-15 | 2011-03-24 | Hy Biopharma, Inc. | Methods for preparing hypericin |
| WO2012081022A1 (en) * | 2010-12-16 | 2012-06-21 | Sensit Science Ltd. | Anthraquinones for use as radiosensitizers in cancer treatment |
| CN102126942A (en) * | 2010-12-22 | 2011-07-20 | 湖北工业大学 | Method for synthesizing hypericin |
| CN102180782A (en) * | 2011-03-23 | 2011-09-14 | 中国农业科学院兰州畜牧与兽药研究所 | Method for synthesizing hypericin |
| CN103274920A (en) * | 2013-06-14 | 2013-09-04 | 西北农林科技大学 | Efficient hypericin synthesizing method initiated by monochromatic light |
| CN104193610A (en) * | 2014-08-05 | 2014-12-10 | 中南大学 | Synthesis method of hypericin |
| CN106588622A (en) * | 2016-12-16 | 2017-04-26 | 陕西嘉禾药业有限公司 | Hypericin synthesis method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111138262A (en) * | 2020-01-13 | 2020-05-12 | 成都金石缘科技有限公司 | Hypericin synthesis method |
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