CN1044455A - The purification process of 2,2 ,-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) - Google Patents
The purification process of 2,2 ,-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) Download PDFInfo
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- CN1044455A CN1044455A CN 89101870 CN89101870A CN1044455A CN 1044455 A CN1044455 A CN 1044455A CN 89101870 CN89101870 CN 89101870 CN 89101870 A CN89101870 A CN 89101870A CN 1044455 A CN1044455 A CN 1044455A
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- naphthaldehyde
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- propyl
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Abstract
The present invention relates to organic chemistry filed.
Method of the present invention is, 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) purifying is by the ethane that adds 0.25-3 times of volume (pressing the volume ratio with ether), with 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) from being the diethyl ether solution of 0.02-0.2 grams per milliliter, its concentration crystallizes out, mixture is placed down at 10-30 ℃, isolated formed precipitation and be dried, until obtaining the purpose product.
The present invention can be applicable in the medical practice.
Description
The present invention relates to organic chemistry filed, relate to 2 or rather, 2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) purification process, this compound can be used as the active substance of the medicament of antineoplastic, antiviral, immunosuppressive action and anti-fertility effect.
Being called 2,2 of gossypol '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) can produce by the crust of Radix Gossypii or by the byproduct after the cotton seed processing.Can make various medicaments with 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) for basic raw material.Wherein, contain its liniment of 3% and can be used to treat viral dermatosis and membrane disease, also can be used to treat conjunctivitis.
Known a kind of purifying 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) method is by it is crystallized out from organic solvent, separate the crystalline deposit and the drying that form, until obtaining purpose product (Journal of the American Chemical Society, V.59, No 5,1937, K.N.Campbell, R.C.Morris, Roger Adams " The Structure of Gdssypol I ", P.1723-1728).
According to the method, 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) are dissolved in the ether, add down isopyknic sherwood oil, under 20 ℃ and vacuum, concentrate, until beginning to form crystalline deposit at 30-60 ℃.And then add sherwood oil and mixture was placed 1 hour.Precipitation is leached and drying, until obtaining the purpose product.2,2 '-two (1 of being obtained, 6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) can be used in the pharmaceutical industry.
Yet, adopt 2,2 of this method purifying '-twos' (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) toxicity always unstable.Its toxicity may surpass the permission standard, and this just makes that the application of this material aspect medicine component is complicated.
Also have a kind of purifying 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) currently known methods, this method is that it is crystallized out from organic solvent, separates the crystalline deposit and the drying that form, until obtaining purpose product (SU.A.1351915).
According to the method, gossypol acetate is dissolved in the acetone.Add activated carbon in the solution and stirred 10-15 minute.Carbon is leached and on strainer, uses washing with acetone.Filtrate is heated to 50-55 ℃ and under agitation at leisure toward wherein adding entry, and then is heated to 55-60 ℃.After 2 hours the close grain of separating out precipitation is leached, wash with water and 60 ℃ of following vacuum-dryings 6 hours.2,2 of medical practice '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) have been obtained to be suitable for.
Yet it also is unsettled adopting 2,2 of this method purifying '-twos' (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) toxicity, and may surpass the permission standard.
Task of the present invention is, obtains hypotoxic stable neat compounds 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) by the method that changes purifying process.
This task is to solve like this, purifying 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) in the method, it is crystallized out from organic solvent, separate formed crystalline deposit and be dried, until obtaining the purpose product.According to the present invention, from concentration is 2 of 0.02-0.2 grams per milliliter, 2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) carries out crystallization in the diethyl ether solution, in this solution, add and be equivalent to ether volume 0.25-3 hexane doubly, then the gained mixture is placed to crystallisation process under 10-30 ℃ and finishes.
Use the purifying of recommending 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) method can obtain a kind of hypotoxic stable purified product, because this method provides the possibility that this compound is separated with a kind of hypotoxic unique crystal formation metamorphosis.
This method can realize by following mode:
With 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) is dissolved in the ether, makes its concentration reach the 0.02-0.2 grams per milliliter, add and be equivalent to ether volume 0.25-3 hexane doubly, obtaining mixture is placed down at 10-30 ℃, finished until crystallisation process.Then the throw out that generates is separated and drying, until obtaining the purpose product.
If 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) concentration in diethyl ether solution surpasses 0.2 grams per milliliter, then in the purpose product, just begin to occur amorphous phase.
If 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) concentration in diethyl ether solution is lower than 0.02 grams per milliliter, then when wherein adding hexane (0.25-3 that quantity is equivalent to the ether volume doubly), the output of this gossypol with unique crystal formation metamorphosis is very little.
If the hexane that adds in the diethyl ether solution of 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) surpasses 3 times of the ether volume, the purpose product that is then obtained will be the mixture of crystallization phases and amorphous phase.
Place if after adding hexane, obtaining mixture is being lower than under 10 ℃ the temperature, then also same phenomenon can take place.
Place if after adding hexane, obtaining mixture is being higher than under 30 ℃ the temperature, then because the ether violent evaporation, 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) concentration in ether will be above 0.2 grams per milliliter, therefore, as mentioned above, in the purpose product, begin to occur amorphous phase.
If the hexane that adds in the diethyl ether solution of 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) is less than 0.25 times of the ether volume, the output of the abnormal product of then unique crystal formation is just very little.
In order to understand the present invention better, be listed below embodiment.
Embodiment 1
1 gram, 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) are dissolved in 5 milliliters of ether, add 15 milliliters of hexanes and under 17-18 ℃ temperature, place, until the end of precipitation generative process.The precipitation of separating out leached and dry under vacuum, until obtaining the purpose product.2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) of the unique crystal formation metamorphosis that is obtained have following lattice parameter: a=20.721(5)
; B=26.018(4)
; C=27.957(5)
; γ=96.83(2)
; V=14965(5)
3; Space crystal group B2/b.
Give mouse oral obtaining purpose product, test the acute toxicity of this product with this, institute obtains and the results are shown in the following table.
Embodiment 2
1 gram, 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) are dissolved in 50 milliliters of ether, add 50 milliliters of hexanes and under 28-30 ℃ temperature, place, until the end of precipitation generative process.
Formed crystalline deposit leached and dry under vacuum, until obtaining the purpose product.2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) of the unique crystal formation metamorphosis of gained have following lattice parameter: a=13.467(1)
; B=8.794(1)
; C=21.376(3)
; γ=97.22(1)
; V=2511(0.5)
3; Space crystal group P2
1/ b.Give mouse oral obtaining purpose product, test the acute toxicity of this product with this, institute obtains and the results are shown in the following table.
Embodiment 3
1 gram, 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) are dissolved in 20 milliliters of ether, add 5 milliliters of hexanes and the gained mixture is placed under 10-12 ℃ temperature, until the end of precipitation generative process.Formed crystalline deposit leached and dry under vacuum, until obtaining the purpose product.
2,2 of unique crystal formation metamorphosis '-two that obtain (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) have following lattice parameter: a=8.557(2)
; B=14.474(5)
; C=25.651(5)
; β=107.22(2)
; V=3035(1,2)
3; Space crystal group P2
1/ C.
Obtaining purpose product is carried out acute toxicity test, and institute obtains and the results are shown in the following table.
2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) shown acute toxicity when giving mouse oral
Test number obtained product medium lethal dose (LD
50) milligram/kilogram
1 embodiment, 1 640(450-768)
2 embodiment 2 are greater than 1500
3 embodiment, 3 750(646-870)
4 currently known methods 383(340-426)
（SU.A.1351915）
Claims (1)
- 2,2 '-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) purification process, this method is that it is crystallized out from organic solvent, isolate formed crystalline deposit and be dried, until obtaining the purpose product, it is characterized in that, be 2,2 of 0.02-0.2 grams per milliliter '-two (1 from concentration, 6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) carry out crystallization in the diethyl ether solution, adding is equivalent to 0.25-3 times hexane of ether volume and obtaining mixture is placed under 10-30 ℃ temperature in this solution, finishes until crystallisation process.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89101870 CN1044455A (en) | 1989-01-25 | 1989-01-25 | The purification process of 2,2 ,-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89101870 CN1044455A (en) | 1989-01-25 | 1989-01-25 | The purification process of 2,2 ,-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) |
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| Publication Number | Publication Date |
|---|---|
| CN1044455A true CN1044455A (en) | 1990-08-08 |
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| CN 89101870 Pending CN1044455A (en) | 1989-01-25 | 1989-01-25 | The purification process of 2,2 ,-two (1,6,7-trihydroxy--3-methyl-5-sec.-propyl-8-naphthaldehyde) |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7342046B2 (en) | 2004-03-25 | 2008-03-11 | The Regents Of The University Of Michigan | Gossypol co-crystals and the use thereof |
| US7354928B2 (en) | 2001-11-01 | 2008-04-08 | The Regents Of The University Of Michigan | Small molecule inhibitors targeted at Bcl-2 |
| CN100413493C (en) * | 2003-06-11 | 2008-08-27 | 中国科学院动物研究所 | Use of gossypol and its derivative in preparation of drug for leukemia / bone marrow cancer |
| CN105125536A (en) * | 2015-07-29 | 2015-12-09 | 江南大学 | Composition for treating dermatoses caused by bacteria, fungi, viruses or parasites |
-
1989
- 1989-01-25 CN CN 89101870 patent/CN1044455A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7354928B2 (en) | 2001-11-01 | 2008-04-08 | The Regents Of The University Of Michigan | Small molecule inhibitors targeted at Bcl-2 |
| CN100413493C (en) * | 2003-06-11 | 2008-08-27 | 中国科学院动物研究所 | Use of gossypol and its derivative in preparation of drug for leukemia / bone marrow cancer |
| US7342046B2 (en) | 2004-03-25 | 2008-03-11 | The Regents Of The University Of Michigan | Gossypol co-crystals and the use thereof |
| CN105125536A (en) * | 2015-07-29 | 2015-12-09 | 江南大学 | Composition for treating dermatoses caused by bacteria, fungi, viruses or parasites |
| CN105125536B (en) * | 2015-07-29 | 2018-05-04 | 无锡宏瑞生物医药科技有限公司 | Treat bacterium, fungi, virus or dermopathic composition caused by parasite |
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