CN109705068A - Protoanemonin synthetic method - Google Patents
Protoanemonin synthetic method Download PDFInfo
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- CN109705068A CN109705068A CN201910146479.2A CN201910146479A CN109705068A CN 109705068 A CN109705068 A CN 109705068A CN 201910146479 A CN201910146479 A CN 201910146479A CN 109705068 A CN109705068 A CN 109705068A
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Abstract
The present invention provides a kind of protoanemonin synthetic methods, it is characterised in that: using 2- methylfuran as starting material, obtains 5- methyl -5- hy droxy furan -2- ketone through peroxidization, 5- methyl -5- hy droxy furan -2- ketone obtains product using dehydration.Synthetic method provided by the invention only needs two-step reaction, and operation is easy, and without using poisonous and harmful substances such as bromines, 65% or more can be reached by reducing murder by poisoning and pollution, two step total recoverys, and high income, raw material are easy to get, at low cost.
Description
Technical field
The present invention relates to a kind of protoanemonin synthetic methods, belong to organic synthesis field.
Background technique
Anemonin (Anemonin), alias: anemonin etc..Molecular formula: C10H8O4, molecular weight: 192.171, CAS
Accession number: 508-44-1, structural formula are as follows:
Anemonin is a kind of native compound, has the effects that anticancer, resisting pathogenic microbes, is widely present in Ranunculaceae
In the various plants the such as plant Chinese bulbul Pulsatilla chinensis (Bge.) Regel.At present mainly by acquisition is extracted, still
Its property is indefinite, it is difficult to extract separation.
Protoanemonin is the primary raw material for synthesizing Anemonin, and the current synthetic method of protoanemonin has:
1, β acrylic acid method, synthetic route are as follows:
This method raw material is simple and easy to get, is widely used, still, it was reported that its reproducibility has certain problems, and obtains product
It needs to be related to some many and diverse to isolate and purify process.
2, photooxidation synthetic method, synthetic route are as follows:
Starting material carries out photooxidation in dehydrated alcohol, using sephadex tetrachloro tetraiodo fluorescer resin as light sensation
Swash, obtain lactone a and b, ratio 70:30 is not purified, and is directly used in next step, then a and b change in sodium hydrate aqueous solution
Sodium borohydride reaction, obtains intermediate 2, is finally dehydrated in the aqueous solution of sodium acetate again, obtains protoanemonin, total recovery
25%, condition needed for this method photooxidation is harsh.
3,2- desoxy-D-ribose method, preparation process are as follows:
The method conveniently, safely, fast, eliminate many intermediate purification processes, yield is relatively high, but raw material 2- de-
Oxygen-D ribose is expensive.
4, alpha-angelica lactone method, synthetic route are as follows:
Using levulic acid as raw material, reaction condition is easy to accomplish, but main problem is, (1) bromine participates in reaction, low
Temperature, and bromine severe toxicity, bad operation.(2) in final step synthesis, the first molecule hydrobromic acid is easily eliminated, and the second molecular hydrogen bromine
Acid is but difficult to eliminate, and yield is low.
For this purpose, the use of a kind of high income, the poisonous and harmful reactive material of reduction is developed, the simple protoanemonin of route
Synthetic method is our problems in urgent need to solve.
Summary of the invention
In order to solve the above-mentioned technical problem, the purpose of the present invention is to provide a kind of protoanemonin synthetic method, yields
Height, route simplify, and reduce and poison and pollute.
In order to realize above-mentioned purpose of the invention, the present invention provides a kind of protoanemonin synthetic method, feature exists
In: using 2- methylfuran as starting material, 5- methyl -5- hy droxy furan -2- ketone (intermediate Z1) is obtained through peroxidization,
5- methyl -5- hy droxy furan -2- ketone obtains product using dehydration.
Synthetic route are as follows:
In above scheme: oxidation reaction are as follows:
2- methylfuran is added in reaction vessel, while organic solvent is added, is added with stirring sodium dihydrogen phosphate and water,
Continue to stir, add anhydrous sodium chlorite, connect reflux unit on the reaction vessel, be stirred to react, until reaction is no longer put
Heat, stratification remove water layer and salinity, collect organic phase, obtain 5- using column chromatography for separation after organic phase solvent is evaporated
Methyl -5- hy droxy furan -2- ketone.
The molar ratio of 2- methylfuran and sodium dihydrogen phosphate and anhydrous sodium chlorite is 1:1.5:3.
In above scheme: the organic solvent is the tert-butyl alcohol.
In above scheme: chromatographic column used in column chromatography for separation uses silica gel as filler, and mobile phase is methanol: methylene chloride 1:
9。
In above scheme: the dehydration are as follows: 5- methyl -5- hy droxy furan -2- ketone is dissolved in anhydrous chloroform, is controlled
10-15 DEG C of temperature, strong acid is added dropwise, is vigorously stirred reaction until the reaction is complete.
In above scheme, the strong acid is trifluoroacetic acid, and organic solvent is distilled off after having reacted and obtains product original hoary hair
Weng Su.It is more easier using trifluoroacetic acid post-processing.
In above scheme, the molar ratio of the 5- methyl -5- hy droxy furan -2- ketone and trifluoroacetic acid is 1:2.
In above scheme, the strong acid is the concentrated sulfuric acid, and the 5- methyl -5- hy droxy furan -2- ketone and trifluoroacetic acid rub
You add water washing after having reacted, collect organic phase, chloroform is distilled off, obtains product than being 1:2.
In above scheme, the dehydration time is 2-3h.So that reaction sufficiently carries out.
In above scheme, the processing method of anhydrous chloroform are as follows: 3A molecular sieve is added in chloroform and is carried out dehydrating.Sufficiently
The moisture in chloroform is handled, so that dehydration is easier to carry out.
The utility model has the advantages that synthetic method provided by the invention only needs two-step reaction, operation is easy, toxic without using bromine etc.
Harmful substance reduces and poisons and pollute, and two step total recoverys can reach 65% or more, and high income, raw material are easy to get, at low cost.
Specific embodiment
Following example is described further the present invention.
Embodiment 1
The preparation of intermediate Z1:
In 1000ml there-necked flask, 8.2g (0.1mol) 2- methylfuran is put into, the 420ml tert-butyl alcohol is added with stirring
20.5g (0.15mol) sodium dihydrogen phosphate and 80g water stir 10min, anhydrous sodium chlorite 27g (0.3mol) are added, connects back
It flows device (return pipe), is vigorously stirred 15 minutes, until reaction no longer heat release, mixed liquor is layered, remove water layer and salinity, uncle
After butanol layer is washed with water, solvent is removed, column chromatography for separation (filler silica gel, mobile phase: methanol: methylene chloride 1:9) obtains nothing
Color liquid intermediate Z19.8g.Yield 86%.
Embodiment 2
The preparation of protoanemonin: intermediate Z1 takes 20g (0.175mol) to be dissolved in 875ml chloroform and (makes of 3A molecular sieve
Cross dehydration), 10-15 DEG C of temperature is controlled, is added dropwise trifluoroacetic acid 53.5g (0.35mol), reaction 2 hours is vigorously stirred,
Solvent (trifluoroacetic acid is removed together when distilling) is distilled off, obtains protoanemonin 13.8g, yield 82%.Nuclear magnetic data
It is as follows: 1H-NMR (400MHz, CDCl3), δ 7.44 (d, 1H, J=5.5), 6.30 (m, 1H), 5.27 (s, 1H), 4.90 (d, 1H,
J=2.3).
Embodiment 3
The preparation of protoanemonin: intermediate Z1 takes 20g (0.175mol) to be dissolved in 875ml chloroform and (makes of 3A molecular sieve
Cross dehydration), 10-15 DEG C of temperature is controlled, is added dropwise concentrated sulfuric acid 34.3g (0.35mol), reaction 2 hours is vigorously stirred, it will be anti-
It answers liquid to be washed with water, collects organic phase, solvent is distilled off, obtains protoanemonin 12.7g, yield 75.5%.Nuclear magnetic data
It is as follows: 1H-NMR (400MHz, CDCl3), δ 7.44 (d, 1H, J=5.5), 6.30 (m, 1H), 5.27 (s, 1H), 4.90 (d,
1H, J=2.3).
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that: not
A variety of change, modification, replacement and modification can be carried out to these embodiments in the case where being detached from the principle of the present invention and objective, this
The range of invention is defined by the claims and their equivalents.
Claims (10)
1. a kind of protoanemonin synthetic method, it is characterised in that: using 2- methylfuran as starting material, obtained through peroxidization
To 5- methyl -5- hy droxy furan -2- ketone, 5- methyl -5- hy droxy furan -2- ketone obtains product using dehydration.
2. protoanemonin synthetic method according to claim 1, which is characterized in that oxidation reaction are as follows:
2- methylfuran is added in reaction vessel, while organic solvent is added, is added with stirring sodium dihydrogen phosphate and water, is continued
Stirring, adds anhydrous sodium chlorite, connects reflux unit on the reaction vessel, be stirred to react, until reaction no longer heat release, quiet
Layering is set, water layer and salinity are removed, collects organic phase, 5- methyl-is obtained using column chromatography for separation after organic phase solvent is evaporated
5- hy droxy furan -2- ketone.
3. protoanemonin synthetic method according to claim 2, it is characterised in that: the organic solvent is the tert-butyl alcohol.
4. protoanemonin synthetic method according to claim 3, it is characterised in that: chromatographic column silicon used in column chromatography for separation
Glue is methanol as filler, mobile phase: methylene chloride 1:9.
5. any one of -4 protoanemonin synthetic method according to claim 1, which is characterized in that the dehydration are as follows:
5- methyl -5- hy droxy furan -2- ketone is dissolved in anhydrous chloroform, controls 10-15 DEG C of temperature, strong acid is added dropwise, is vigorously stirred reaction
Until the reaction is complete.
6. protoanemonin synthetic method according to claim 5, it is characterised in that: the strong acid is trifluoroacetic acid, reaction
Organic solvent is distilled off after complete and obtains product protoanemonin.
7. protoanemonin synthetic method according to claim 6, it is characterised in that: the 5- methyl -5- hy droxy furan -2-
The molar ratio of ketone and trifluoroacetic acid is 1:2.
8. protoanemonin synthetic method according to claim 5, it is characterised in that: the strong acid is the concentrated sulfuric acid, the 5-
The molar ratio of methyl -5- hy droxy furan -2- ketone and trifluoroacetic acid is 1:2,
After having reacted plus water washing, collection organic phase are distilled off chloroform, obtain product.
9. protoanemonin synthetic method according to claim 5, it is characterised in that: the dehydration time is 2-3h.
10. protoanemonin synthetic method according to claim 5, which is characterized in that the processing method of anhydrous chloroform are as follows:
3A molecular sieve is added in chloroform to be carried out dehydrating.
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| CN201910146479.2A CN109705068A (en) | 2019-02-27 | 2019-02-27 | Protoanemonin synthetic method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112939893A (en) * | 2019-12-10 | 2021-06-11 | 普济生物科技（台州）有限公司 | Synthesis method of 4- (4-aminophenyl) -3-morpholinone |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB896949A (en) * | 1957-12-14 | 1962-05-23 | Basf Ag | Improvements in the production of proto-anemonin and its homologues |
| CN1688543A (en) * | 2002-08-19 | 2005-10-26 | 拜欧希格诺有限公司 | Furanone derivatives and methods of making same |
-
2019
- 2019-02-27 CN CN201910146479.2A patent/CN109705068A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB896949A (en) * | 1957-12-14 | 1962-05-23 | Basf Ag | Improvements in the production of proto-anemonin and its homologues |
| CN1688543A (en) * | 2002-08-19 | 2005-10-26 | 拜欧希格诺有限公司 | Furanone derivatives and methods of making same |
Non-Patent Citations (2)
| Title |
|---|
| MARTIN POŠTA ET AL.: ""Structure–activity relationships of analogs of 3,4,5-trimethylfuran-2(5H)-one with germination inhibitory activities"", 《JOURNAL OF PLANT PHYSIOLOGY》 * |
| SAGAR S. THORAT ET AL.: ""Four-Step Total Synthesis of (+)-Yaoshanenolides A and B"", 《ACS OMEGA》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112939893A (en) * | 2019-12-10 | 2021-06-11 | 普济生物科技（台州）有限公司 | Synthesis method of 4- (4-aminophenyl) -3-morpholinone |
| CN112939893B (en) * | 2019-12-10 | 2022-08-23 | 普济生物科技（台州）有限公司 | Synthesis method of 4- (4-aminophenyl) -3-morpholinone |
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