CN106518864A - Method for synthesizing rotundine with berberine as raw material - Google Patents
Method for synthesizing rotundine with berberine as raw material Download PDFInfo
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- CN106518864A CN106518864A CN201610974920.2A CN201610974920A CN106518864A CN 106518864 A CN106518864 A CN 106518864A CN 201610974920 A CN201610974920 A CN 201610974920A CN 106518864 A CN106518864 A CN 106518864A
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- China
- Prior art keywords
- palmatine
- berberine
- hydrochloride
- racemization
- rotundine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a method for synthesizing rotundine with berberine as a raw material. The method comprises the steps that (1) berberine hydrochloride is subjected to ring opening to obtain de-methylene berberine hydrochloride; (2) the de-methylene berberine hydrochloride is subjected to methoxylation to obtain palmatine chloride; (3) the palmatine chloride is subjected to racemization to obtain racemized palmatine; and (4) the racemized palmatine is split to obtain tetrahydropalmatine, and dextral-tetrahydropalmatine is split again and generated repeatedly for application. According to the method, the berberine serves as the raw material, the rotundine is obtained through ring opening, splitting, racemization and re-splitting, and the dextral-tetrahydropalmatine is split again and applied repeatedly. The method is easy to implement and feasible, raw materials are low in price, the technological path is short, all intermediate reactions are easy to control, and the cost is low.
Description
Technical field
The invention belongs to pharmaceutical synthesis field, and in particular to a kind of with berberine as Material synthesis rotundine
Method.
Background technology
Tetrahydropalmatine typically adopts guaiacol for initiation material, through methylating, chloromethylation, cyaniding reduction, ring
Close and reduction reaction is obtained, processing step is more, and high cost, yield are low, and the time is long.
The content of the invention
The present invention seeks to a kind of method with berberine as Material synthesis rotundine；Solve original technique step
Rapid many, high cost, yield are low, the problem of time length.
The technical scheme is that：A kind of method with berberine as Material synthesis rotundine, step is such as
Under：
(1) berberine hydrochloride open loop obtains methylene berberine hydrochloride；
(2) methylene berberine hydrochloride methoxylation is gone to obtain palmatine hydrochloride,
(3) palmatine hydrochloride racemization obtains racemization palmatine,
(4) racemization palmatine splits and obtains rotundine and dextrorotation tetrahydropalmatine, and dextrorotation tetrahydropalmatine disappears
Revolve and reuse for palmatine hydrochloride.
Further, the concrete grammar of step (1) is：Berberine hydrochloride is in p-methyl benzenesulfonic acid, dimethylbenzene, HCl, 70 DEG C of bars
Open loop under part obtains methylene berberine hydrochloride.
Further, the concrete grammar of step (2) is：Methylene berberine hydrochloride is removed in potassium carbonate, methanol, dimethyl sulfate
Ester, under the conditions of 40 DEG C, methyl-etherified obtains palmatine hydrochloride.
Further, the concrete grammar of step (3) is：Palmatine hydrochloride racemization under the conditions of methanol, sodium borohydride is obtained
Racemization palmatine.
Further, the concrete grammar of step (4) is：Racemization palmatine is in D- to methyldiphenyl formic acid tartaric acid, dichloro
Split under methane conditions and obtain rotundine and dextrorotation tetrahydropalmatine, dextrorotation tetrahydropalmatine is in methanol, potassium acetate
Under the conditions of racemization be palmatine hydrochloride reuse.
The synthetic route of the present invention is as follows：
The present invention is had the advantage that compared with prior art：
The present invention adopt berberine for raw material, through open loop, fractionation, racemization, splits again and obtains rotundine, the right side
Rotation is returned Jing after racemization and is reused, and the method is simple to operate, easy, and raw materials used cheap, process route is short, and each intermediate is anti-
Should be easy to control, low cost.
Specific embodiment
A kind of method with berberine as Material synthesis rotundine, step are as follows：
(1) berberine hydrochloride open loop obtains methylene berberine hydrochloride；
(2) methylene berberine hydrochloride methoxylation is gone to obtain palmatine hydrochloride,
(3) palmatine hydrochloride racemization obtains racemization palmatine,
(4) racemization palmatine splits and obtains rotundine and dextrorotation tetrahydropalmatine, and dextrorotation tetrahydropalmatine disappears
Revolve and reuse for palmatine hydrochloride.
Embodiment 1
, in p-methyl benzenesulfonic acid, dimethylbenzene, HCl, under the conditions of 70 DEG C, to obtain methylene hydrochloric acid little for open loop for A, berberine hydrochloride
Bark of a cork tree alkali.
B, go methylene berberine hydrochloride in potassium carbonate, methanol, dimethyl sulfate, methyl-etherified obtains hydrochloric acid under the conditions of 40 DEG C
Palmatine.
The racemization under the conditions of methanol, sodium borohydride of C, palmatine hydrochloride obtains racemization palmatine.
D, racemization palmatine split under the conditions of D- is to methyldiphenyl formic acid tartaric acid, dichloromethane and obtain left-handed Rhizoma Corydalis
B prime and dextrorotation tetrahydropalmatine, the racemization under the conditions of methanol, potassium acetate of dextrorotation tetrahydropalmatine are that palmatine hydrochloride repetition makes
With.
Embodiment described above only expresses the specific embodiment of the application, and its description is more concrete and detailed, but and
Therefore the restriction to the application protection domain can not be interpreted as.It should be pointed out that for one of ordinary skill in the art
For, on the premise of conceiving without departing from technical scheme, some deformations and improvement can also be made, these belong to this
The protection domain of application.
Claims (5)
1. a kind of method with berberine as Material synthesis rotundine, it is characterised in that step is as follows：
(1) berberine hydrochloride open loop obtains methylene berberine hydrochloride；
(2) methylene berberine hydrochloride methoxylation is gone to obtain palmatine hydrochloride,
(3) palmatine hydrochloride racemization obtains racemization palmatine,
(4) racemization palmatine splits and obtains rotundine and dextrorotation tetrahydropalmatine, and dextrorotation tetrahydropalmatine racemization is
Palmatine hydrochloride is reused.
2. a kind of method with berberine as Material synthesis rotundine according to claim 1, its feature exist
In the concrete grammar of step (1) is：Berberine hydrochloride is gone in p-methyl benzenesulfonic acid, dimethylbenzene, HCl, open loop under the conditions of 70 DEG C
Methylene berberine hydrochloride.
3. a kind of method with berberine as Material synthesis rotundine according to claim 1, its feature exist
In the concrete grammar of step (2) is：Methylene berberine hydrochloride is removed in potassium carbonate, methanol, dimethyl sulfate, under the conditions of 40 DEG C
Methyl-etherified obtains palmatine hydrochloride.
4. a kind of method with berberine as Material synthesis rotundine according to claim 1, its feature exist
In the concrete grammar of step (3) is：Palmatine hydrochloride racemization under the conditions of methanol, sodium borohydride obtains racemization palmatine.
5. a kind of method with berberine as Material synthesis rotundine according to claim 1, its feature exist
In the concrete grammar of step (4) is：Racemization palmatine is split under the conditions of D- is to methyldiphenyl formic acid tartaric acid, dichloromethane
Rotundine and dextrorotation tetrahydropalmatine are obtained, the racemization under the conditions of methanol, potassium acetate of dextrorotation tetrahydropalmatine is salt
Sour palmatine is reused.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610974920.2A CN106518864A (en) | 2016-10-28 | 2016-10-28 | Method for synthesizing rotundine with berberine as raw material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610974920.2A CN106518864A (en) | 2016-10-28 | 2016-10-28 | Method for synthesizing rotundine with berberine as raw material |
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|---|---|
| CN106518864A true CN106518864A (en) | 2017-03-22 |
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| CN201610974920.2A Pending CN106518864A (en) | 2016-10-28 | 2016-10-28 | Method for synthesizing rotundine with berberine as raw material |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108586451A (en) * | 2018-07-02 | 2018-09-28 | 云南白药集团股份有限公司 | A kind of preparation method of palmatin hydrochloride |
| CN109293654A (en) * | 2018-10-08 | 2019-02-01 | 佑华制药（乐山）有限公司 | A kind of rotundin production technology |
| CN118126034A (en) * | 2024-05-06 | 2024-06-04 | 云南省药物研究所 | Comprehensive utilization method of rotundine splitting mother liquor |
| CN118126034B (en) * | 2024-05-06 | 2024-07-05 | 云南省药物研究所 | Comprehensive utilization method of rotundine splitting mother liquor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1115318A (en) * | 1994-07-20 | 1996-01-24 | 中国科学院上海药物研究所 | Levo- and dextro-rotary chloroscouriline (tetrahydroprotoberberines) and application thereof |
| US20090048246A1 (en) * | 2007-06-22 | 2009-02-19 | Haiyan Liu | Compounds, compositions and methods for reducing lipid levels |
| CN102040604A (en) * | 2010-11-12 | 2011-05-04 | 昆明振华制药厂有限公司 | Fibriuretinin synthesis method |
| CN103145703A (en) * | 2013-01-14 | 2013-06-12 | 李玉山 | Process technique to prepare rotundine based on different plants |
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2016
- 2016-10-28 CN CN201610974920.2A patent/CN106518864A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1115318A (en) * | 1994-07-20 | 1996-01-24 | 中国科学院上海药物研究所 | Levo- and dextro-rotary chloroscouriline (tetrahydroprotoberberines) and application thereof |
| US20090048246A1 (en) * | 2007-06-22 | 2009-02-19 | Haiyan Liu | Compounds, compositions and methods for reducing lipid levels |
| CN102040604A (en) * | 2010-11-12 | 2011-05-04 | 昆明振华制药厂有限公司 | Fibriuretinin synthesis method |
| CN103145703A (en) * | 2013-01-14 | 2013-06-12 | 李玉山 | Process technique to prepare rotundine based on different plants |
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| 霍立等: "罗通定的合成", 《中国医药工业杂志》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108586451A (en) * | 2018-07-02 | 2018-09-28 | 云南白药集团股份有限公司 | A kind of preparation method of palmatin hydrochloride |
| CN108586451B (en) * | 2018-07-02 | 2021-03-12 | 云南白药集团股份有限公司 | Preparation method of palmatine hydrochloride |
| CN109293654A (en) * | 2018-10-08 | 2019-02-01 | 佑华制药（乐山）有限公司 | A kind of rotundin production technology |
| CN118126034A (en) * | 2024-05-06 | 2024-06-04 | 云南省药物研究所 | Comprehensive utilization method of rotundine splitting mother liquor |
| CN118126034B (en) * | 2024-05-06 | 2024-07-05 | 云南省药物研究所 | Comprehensive utilization method of rotundine splitting mother liquor |
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Application publication date: 20170322 |
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