CN107880063A - A kind of synthetic method of dauricine - Google Patents
A kind of synthetic method of dauricine Download PDFInfo
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- CN107880063A CN107880063A CN201711269291.4A CN201711269291A CN107880063A CN 107880063 A CN107880063 A CN 107880063A CN 201711269291 A CN201711269291 A CN 201711269291A CN 107880063 A CN107880063 A CN 107880063A
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- China
- Prior art keywords
- formula
- dauricine
- synthetic method
- maackiain
- formaldehyde
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Abstract
The synthetic method of dauricine, the synthetic method are carried out as follows shown in a kind of formula (III)：Maackiain, formaldehyde, 4 dimethylamino naphthyridines shown in sparteine shown in formula (I), formula (II) are mixed in organic solvent, 2~3h is reacted in 85~95 DEG C, reaction solution is post-treated afterwards, obtains dauricine shown in product formula (III)；Process of preparing of the present invention is simple, takes short, high income；Test result indicates that synthetic method of the present invention, yield is up to more than 73%；(I)(II)
Description
(1) technical field
The present invention relates to a kind of synthetic method of alkaloid, and in particular to one kind has Cytisine-Pterocarpan bones
The synthetic method of the dauricine (Tonkinensine B) of frame.
(2) background technology
Dauricine (Tonkinensine B) is the alkaloid component being present in subprostrate sophora, chemical formula C28H26N2O6,
It has Cytisine-Pterocarpan skeletons, and content is low in subprostrate sophora, and it has not been most that largely from plant prepared by separation
Good selection.Early-stage Study and Literature Consult by us, thus it is speculated that TonkinensineB this there is Cytisine-
The biosynthesis precursor of the compound of Pterocarpan skeletons is respectively sparteine [(-)-cytisine] and maackiain
[(-)-maackiain], compound (-)-cytisine by methylate with oxidative coupling reaction and compound (-)-
Maackiain is connected, and the two precursor compounds content in subprostrate sophora is larger, largely isolated.
Pharmacological research finds that the alkaloid compound in subprostrate sophora has preferable pharmacological activity.Traditional separates, is pure
The shortcomings such as time-consuming, workload is big be present in change method；Again because Structures of Natural Products is more complicated, if with total synthesis method
Synthetic route is grown, and product yield is low, while is also possible to that more noble metal catalyst, and the three-dimensional selection in reaction can be used
Property often turns into very big obstacle, and the yield of final products is relatively low, is unfavorable for preparing on a large scale.With Cytisine-
The compound structure of Pterocarpan skeletons is more complicated, and chiral carbon is more, therefore fully synthetic extremely difficult.
(3) content of the invention
Based on problems of the prior art, by the present invention in that with sparteine [(-)-cytisine] and Koryo
Chinese scholartree element [(-)-maackiain] is reactant, using comparatively gentle reaction condition, shortens reaction scheme as far as possible, right
Cytisine-Pterocarpan skeletons carry out bio-mimetic syntheses, so as to realize substantial amounts of acquisition target compound dauricine
(Tonkinensine B), facility is provided for the further further investigation of the type compound.
Technical scheme is as follows：
The synthetic method of dauricine, the synthetic method are carried out as follows shown in a kind of formula (III)：
Maackiain, formaldehyde, DMAP (DMAP) shown in sparteine shown in formula (I), formula (II) are being had
Mixed in solvent, react 2~3h in 85~95 DEG C (preferably 93 DEG C), reaction solution is post-treated afterwards, obtains product formula (III)
Shown dauricine.
Sparteine shown in the formula (I), maackiain, formaldehyde, the thing that feeds intake of DMAP shown in formula (II)
The ratio between amount of matter is 1.5~2：1：1.5~2：0.02~0.03；
The quality dosage of the organic solvent is 25~35 times of maackiain quality shown in formula (II)；
The formaldehyde is fed intake in the form of the 37wt% aqueous solution；
The organic solvent is isopropanol or dioxanes；
The method of reaction solution post processing is：After reaction terminates, reaction solution is concentrated under reduced pressure, then with 200~300 mesh silicon
Glue carries out column chromatography for separation, with volume ratio 30：1 methylene chloride/methanol mixed liquor is eluant, eluent, is collected containing target compound
Eluent, remove solvent and drying under reduced pressure, produce target product.
cytisine
maackiain
Tonkinensine B
The beneficial effects of the present invention are：Compared with traditional extraction method, process of preparing of the present invention is simple, takes
It is short, high income.Test result indicates that synthetic method of the present invention, yield is up to more than 73%.
(4) illustrate
Fig. 1：Tonkinensine B prepared by embodiment 1 hydrogen nuclear magnetic resonance spectrogram.
(5) embodiment
Below by specific embodiment, the invention will be further described, but protection scope of the present invention is not limited in
This.
Embodiment 1
Maackiain (56.8mg, 0.2mmol) is dissolved in isopropanol (2ml), sequentially adds sparteine
(57.1mg, 0.3mmol), 37% formaldehyde (30ul, containing formaldehyde 0.4mmol), DMAP (0.5mg, 0.004mmol), returned in 85 DEG C
3h is flowed, after reaction terminates, reaction solution decompression is spin-dried for, separated with 200-300 mesh silicagel columns, eluant, eluent is dichloromethane：
Methanol=30：The mixed solvent of 1 (volume ratio), the eluent containing target compound is collected, decompression is spin-dried for obtaining beige solid,
Product quality is 60.8mg, yield 62.5%.
1H-NMR(CDCl3,600MHz)δ:7.28 (dd, J1=6.8Hz, J2=9.2Hz), 7.21 (d, J=8.4Hz),
6.70 (s), 6.52 (dd, J1=1.2Hz, J2=9.2Hz), 6.44 (d, J=8.4Hz), 6.40 (s), 5.98 (dd, J1=
1.2Hz, J2=6.8), 5.90 (d, J=1.6Hz), 5.88 (d, J=1.6Hz), 5.42 (d, J=6.4Hz), 5.29 (s),
4.17 (dd, J1=4.8Hz, J2=11.2Hz), 4.13 (br d, J=16.0Hz), 3.89 (dd, J1=6.4Hz, J2=
16.0Hz), 3.70 (d, J=14.4Hz), 3.66 (d, J=14.4 Hz), 3.55 (t, J=11.2Hz), 3.40 (m), 3.10
(br d, J=11.2Hz), 3.02 (m), 2.99 (m), 2.50 (br s), 2.44 (m), 2.39 (br d, J=11.2Hz),
1.95 (br, d, J=12.8Hz), 1.84 (br, d, J=12.8Hz)
Embodiment 2
Maackiain (56.8mg, 0.2mmol) is dissolved in dioxanes (2ml), sequentially adds sparteine
(57.1mg, 0.3mmol), 37% formaldehyde (30ul, containing formaldehyde 0.4mmol), DMAP (0.5mg, 0.004mmol), returned in 93 DEG C
2h is flowed, after reaction terminates, reaction solution decompression is spin-dried for, separated with 200-300 mesh silicagel columns, eluent is dichloromethane：
Methanol=30：The mixed solvent of 1 (volume ratio), the eluent containing target compound is collected, decompression is spin-dried for obtaining beige solid,
Product quality is 67.8mg, yield 69.7%.
1H-NMR(CDCl3,600MHz)δ:7.28 (dd, J1=6.8Hz, J2=9.2Hz), 7.21 (d, J=8.4Hz),
6.70 (s), 6.52 (dd, J1=1.2Hz, J2=9.2Hz), 6.44 (d, J=8.4Hz), 6.40 (s), 5.98 (dd, J1=
1.2Hz, J2=6.8), 5.90 (d, J=1.6Hz), 5.88 (d, J=1.6Hz), 5.42 (d, J=6.4Hz), 5.29 (s),
4.17 (dd, J1=4.8Hz, J2=11.2Hz), 4.13 (br d, J=16.0Hz), 3.89 (dd, J1=6.4Hz, J2=
16.0Hz), 3.70 (d, J=14.4Hz), 3.66 (d, J=14.4 Hz), 3.55 (t, J=11.2Hz), 3.40 (m), 3.10
(br d, J=11.2Hz), 3.02 (m), 2.99 (m), 2.50 (br s), 2.44 (m), 2.39 (br d, J=11.2Hz),
1.95 (br, d, J=12.8Hz), 1.84 (br, d, J=12.8Hz)
Embodiment 3
Maackiain (56.8mg, 0.2mmol) is dissolved in dioxanes (2ml), sequentially adds sparteine
(76.1mg, 0.4mmol), 37% formaldehyde (30ul, containing formaldehyde 0.4mmol), DMAP (0.5mg, 0.004mol), returned in 93 DEG C
2.5h is flowed, after reaction terminates, reaction solution decompression is spin-dried for, separated with 200-300 mesh silicagel columns, eluent is dichloromethane
Alkane：Methanol=30：The mixed solvent of 1 (volume ratio), collects the eluent containing target compound, and decompression, which is spin-dried for obtaining rice white, consolidates
Body, product quality 71.6mg, yield 73.6%.
1H-NMR(CDCl3,600MHz)δ:7.28 (dd, J1=6.8Hz, J2=9.2Hz), 7.21 (d, J=8.4Hz),
6.70 (s), 6.52 (dd, J1=1.2Hz, J2=9.2Hz), 6.44 (d, J=8.4Hz), 6.40 (s), 5.98 (dd, J1=
1.2Hz, J2=6.8), 5.90 (d, J=1.6Hz), 5.88 (d, J=1.6Hz), 5.42 (d, J=6.4Hz), 5.29 (s),
4.17 (dd, J1=4.8Hz, J2=11.2Hz), 4.13 (br d, J=16.0Hz), 3.89 (dd, J1=6.4Hz, J2=
16.0Hz), 3.70 (d, J=14.4Hz), 3.66 (d, J=14.4 Hz), 3.55 (t, J=11.2Hz), 3.40 (m), 3.10
(br d, J=11.2Hz), 3.02 (m), 2.99 (m), 2.50 (br s), 2.44 (m), 2.39 (br d, J=11.2Hz),
1.95 (br, d, J=12.8Hz), 1.84 (br, d, J=12.8Hz).
Claims (5)
1. the synthetic method of dauricine shown in a kind of formula (III), it is characterised in that the synthetic method is entered as follows
OK：
Maackiain, formaldehyde, DMAP shown in sparteine shown in formula (I), formula (II) are mixed in organic solvent
Close, react 2~3h in 85~95 DEG C, reaction solution is post-treated afterwards, obtains dauricine shown in product formula (III)；
Sparteine shown in the formula (I), maackiain shown in formula (II), formaldehyde, the material that feeds intake of DMAP
The ratio between amount is 1.5~2：1：1.5~2：0.02~0.03；
The organic solvent is isopropanol or dioxanes；
2. the synthetic method of dauricine as claimed in claim 1, it is characterised in that reaction temperature is 93 DEG C.
3. the synthetic method of dauricine as claimed in claim 1, it is characterised in that the quality dosage of the organic solvent is formula
(II) 25~35 times of maackiain quality shown in.
4. the synthetic method of dauricine as claimed in claim 1, it is characterised in that the formaldehyde is with the shape of the 37wt% aqueous solution
Formula is fed intake.
5. the synthetic method of dauricine as claimed in claim 1, it is characterised in that the method for reaction solution post processing is：
After reaction terminates, reaction solution is concentrated under reduced pressure, and then column chromatography for separation is carried out with 200~300 mesh silica gel, with volume ratio 30：The two of 1
Chloromethanes/methyl alcohol mixed liquor is eluant, eluent, collects the eluent containing target compound, removes solvent and drying under reduced pressure, produces mesh
Mark product.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711269291.4A CN107880063B (en) | 2017-12-05 | 2017-12-05 | A kind of synthetic method of dauricine |
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| CN201711269291.4A CN107880063B (en) | 2017-12-05 | 2017-12-05 | A kind of synthetic method of dauricine |
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| CN107880063B CN107880063B (en) | 2019-05-28 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110804056A (en) * | 2019-11-06 | 2020-02-18 | 浙江工业大学 | Compound with cytisine-flavonoid skeleton and synthesis method and application thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970738B (en) * | 2019-02-27 | 2021-07-09 | 上海工程技术大学 | Caragana N-isoflavone compound and preparation method and application thereof |
-
2017
- 2017-12-05 CN CN201711269291.4A patent/CN107880063B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| XING-NUO LI ET AL.: "Tonkinensines A and B, two novel alkaloids from Sophora tonkinensis", 《TETRAHEDRON LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110804056A (en) * | 2019-11-06 | 2020-02-18 | 浙江工业大学 | Compound with cytisine-flavonoid skeleton and synthesis method and application thereof |
| CN110804056B (en) * | 2019-11-06 | 2020-11-13 | 浙江工业大学 | Compound with cytisine-flavonoid skeleton and synthesis method and application thereof |
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| Publication number | Publication date |
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| CN107880063B (en) | 2019-05-28 |
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