CN102532249A - 1-chloro tanshinone compound and preparation method thereof - Google Patents
1-chloro tanshinone compound and preparation method thereof Download PDFInfo
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- CN102532249A CN102532249A CN2010106048294A CN201010604829A CN102532249A CN 102532249 A CN102532249 A CN 102532249A CN 2010106048294 A CN2010106048294 A CN 2010106048294A CN 201010604829 A CN201010604829 A CN 201010604829A CN 102532249 A CN102532249 A CN 102532249A
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Abstract
The invention discloses a 1-chloro tanshinone compound and simultaneously discloses a preparation method of the 1-chloro tanshinone compound. The structure general formula of the 1-chloro tanshinone compound is as follows: and the 1-chloro tanshinone compound provided by the invention is obtained by introducing a chlorine atom into a 1-position of the tanshinone compound, and the 1-chloro tanshinone compound obtained by chloro is easy to carry out chemical reaction and can be convenient to convert to other products. Therefore, the invention provides a referenced solving method for problem that the tanshinone compounds with unique molecular structures are difficult to carry out structural modification, and simultaneously provides a new way for the full development of medicinal values of the tanshinone compounds.
Description
Technical field
The invention belongs to the pharmaceutical intermediate technical field, be specifically related to 1-chloro tanshinone compound and preparation method thereof.
Background technology
The red sage root be lip type section mouse tail belong to the per nnial herb red sage root (
SaiviamiItiorrhizaBunge) dry rhizome.Red sage root bitter is slightly cold, and goes into the heart, pericardium, Liver Channel.In the treatment of Chinese medicine, the red sage root can be used for menoxenia, through closing dysmenorrhoea, and the various pain due to the hemostasis, a lump in the abdomen causing distension and pain, and the swollen bitterly and palpitation and insomnia of sore etc. are clinical common drug.Modern clinical experiment and pharmacological experiment study confirm the pharmacological action of the red sage root be mainly reflected in provide protection to heart, to the provide protection of liver, to the provide protection of cerebral tissue, can improve spinal cord microcirculation raising myeloid tissue hypoxia-bearing capability, antitumor action, to the improvement effect of blood viscosity, improve the renal function effect and to the aspects such as provide protection of skin.The chemical ingredients of the red sage root can be divided into fat-soluble and water-soluble two portions; Fat-soluble part is main with the diterpene quinone of TANSHINONES type; On chemical structure, all contain o-quinone or para-quinoid structure; Isolated tens of kinds of tanshinone compounds at present, wherein Tanshinone I, tanshinone IIA, the content of VSZ3505 in the herbal medicine red sage root are all higher; Water-soluble portion is mainly phenolic acid compound, comprises Salvianic acidA, rancinamycin IV etc.
Tanshinone compound is the effective constituent of the red sage root; Has multiple pharmacological effect; Except that effect with traditional promoting blood flow to regulate menstruation, stasis-dispelling and pain-killing, tranquilizing by nourishing the heart; Anti-oxidant, antibiotic to it in recent years, anti-inflammatory, blood viscosity lowering, anticoagulant, promotion fibrinolytic, anticoagulant, prolongation thrombosis and promote thrombolytic effect; Liver protecting, antitumor, regulate body's immunity and improve Pharmacological action study such as anti-diabetic microvascular complication also day by day deeply, make tanshinone compound have boundless potential applicability in clinical practice.But because tanshinone compound is fat-soluble component, water insoluble, its bioavailability in vivo is low; So tanshinone compound is carried out structural modification; Strengthening that it is water-soluble, so that process various pharmaceutical dosage forms, is the optimum method of giving full play to the tanshinone compound pharmacological action.It is water-soluble or strengthen its pharmacologically active to strengthen it how on tanshinone compound, to introduce group, is the key issue that present tanshinone compound uses thereby the pharmaceutical use of tanshinone compound is not fully exerted.
Summary of the invention
The object of the present invention is to provide a kind of 1-chloro tanshinone compound.
Simultaneously, the present invention also aims to provide a kind of preparation method of 1-chloro tanshinone compound.
In order to realize above purpose, the technical scheme that the present invention adopted is: a kind of 1-chloro tanshinone compound, and general structure is:
Wherein, R
1Be to be selected from arbitrarily-CH
3,-OH ,-a kind of among the H,
R
2Be to be selected from arbitrarily-CH
3,-CH
2OH ,-COOCH
3A kind of among the ,-CHO,
R
3Be be selected from arbitrarily-OH ,-a kind of among the H,
R
4Be to be selected from 3-CH arbitrarily
3-furyl, 3-CH
3-2, the 3-2H-furyl ,-CH (CH
3)
2, 3-CH
2A kind of in the OH-furyl.
Described 1-chloro tanshinone compound for example can be any in 1-Cl-tanshinone IIA, 1-Cl-VSZ3505,1-Cl-tanshinone, 1-Cl-Methyl tanshinonate, 1-Cl-Rosmariquinone, 1-Cl-Tanshindiol A, 1-Cl-3 α-OH-tanshinone IIA, 1-Cl-Przewatanshinquinone A, 1-Cl-prezewaquinone C element, 1-Cl-prezewaquinone D element, 1-Cl-prezewaquinone E element, 1-Cl-red sage root aldehyde, 1-Cl-Isotanshinone A and the different VSZ3505 of 1-Cl-.
A kind of preparation method of 1-chloro tanshinone compound may further comprise the steps: with AlCl
3Put into solvent stirring reaction half a hour with acyl chlorides, add tanshinone compound afterwards again, continued stirring reaction at ambient temperature 3～5 hours, make the 1-Cl-tanshinone compound, the general structure of wherein said tanshinone compound is:
Wherein, R
1Be to be selected from arbitrarily-CH
3,-OH ,-a kind of among the H,
R
2Be to be selected from arbitrarily-CH
3,-CH
2OH ,-COOCH
3A kind of among the ,-CHO,
R
3Be be selected from arbitrarily-OH ,-a kind of among the H,
R
4Be to be selected from 3-CH arbitrarily
3-furyl, 3-CH
3-2, the 3-2H-furyl ,-CH (CH
3)
2, 3-CH
2A kind of in the OH-furyl.
Described acyl chlorides is a kind of in Benzoyl chloride 99min., furoyl chloride, paranitrobenzoyl chloride, m-nitrobenzoyl chloride, the Acetyl Chloride 98Min..
Described solvent is methylene dichloride, chloroform, toluene or THF.
Said AlCl
3, acyl chlorides and tanshinone compound mol ratio be: AlCl
3: acyl chlorides: tanshinone compound=(0.1～10): (0.1～10): 1.
1-chloro tanshinone compound provided by the invention makes through 1 introducing chlorine atom at tanshinone compound; Chemical reaction takes place in 1-chloro tanshinone compound easily that behind chloro, make; Can be converted into other products very easily; The problem that is difficult to carry out structural modification for the tanshinone compound of unique molecular structure provides a kind of solution that can reference, is also developed a kind of new approach that provides fully for the pharmaceutical use of tanshinone compound simultaneously.The preparation method of 1-chloro tanshinone compound of the present invention is simple, and productive rate is high, and productive rate is 70～85%, and desired raw material is easy to get, and reaction conditions is gentle, and cost is low, operational safety, and the product purity of acquisition is high, has better industrial application prospect.
Embodiment
Embodiment 1
The 1-Cl-tanshinone IIA, structural formula is:
The preparation method of 1-Cl-tanshinone IIA: the aluminum chloride, the Benzoyl chloride 99min. of 0.3mmol and the methylene dichloride of 2ml that in there-necked flask, add 0.3mmol; The tanshinone IIA that adds 0.1mmol at 25 ℃ of stirring reactions after half a hour; Continued stirring reaction again 3 hours, reaction finishes back CH
2Cl
2Layer is washed 2 times with equal-volume 5% sodium hydrogen carbonate solution earlier with isopyknic washing 3 times again, with washing neutrality, tells organic phase at last; Use anhydrous magnesium sulfate drying, filter, concentrate; Use sherwood oil/acetone=8:1 to carry out rapid column chromatography as eluent, obtain the 1-Cl-tanshinone IIA, productive rate is 75%.The 1-Cl-tanshinone IIA
1H NMR (
δ, CDCl
3): 7.69 (2H, s), 7.24 (1H, m), 6.62 (1H, t), 2.34-2.17 (3H, m), 2.26 (3H, m), 1.6 (1H, m), 1.25 (3H, s), 1.4 (3H, s);
13C NMR (δ, CDCl
3): 182,75,174.59,160.94,148.71,141.64,140.75,134.53,128.56,124.83,122.95,121.37,120.21,54.15,34.77,32.00,31.92,31.63,28.37,8.7; Mass spectrum (m/z): 351.9146.
Embodiment 2
The 1-Cl-VSZ3505, structural formula is:
The preparation method of 1-Cl-VSZ3505: in there-necked flask, add the aluminum chloride of 0.1mmol, m-nitrobenzoyl chloride and the 2ml chloroform of 0.1mmol; 25 ℃ of stirring reaction half a hour; The VSZ3505 that adds 1mmol afterwards continued to react 5 hours again, and reaction finishes back CH
2Cl
2Layer is washed 2 times with equal-volume 5% sodium hydrogen carbonate solution earlier with isopyknic washing 3 times again, with washing neutrality, tells organic phase at last; Use anhydrous magnesium sulfate drying, filter, concentrate; Use sherwood oil/acetone=8:1 to carry out rapid column chromatography as eluent, obtain the 1-Cl-VSZ3505, productive rate is 80%.The 1-Cl-VSZ3505
1H NMR (δ, CDCl
3): 7.7 (1H, d), 7.6 (1H, d), 6.628 (1H, m), 4.9 (1H, dd); 4.4 (1H, dd), 3.6 (1H, m), 2.34-2.17 (3H, m), 2.26 (3H, m); 1.6 (1H, m), 1.26 (3H, s), 1.44 (3H, s), 1.36 (3H, d);
13C NMR (δ, CDCl
3): 183.34,174.69,170.14,150.89,140.17,133.69,130.19,128.49,125.12,118.66,81.57,53.90,34.96,34.69,32.20,31.88,31.64,28.33,18.86.
Embodiment 3
The 1-Cl-Methyl tanshinonate, structural formula is:
The preparation method of 1-Cl-Methyl tanshinonate: in there-necked flask, add the aluminum chloride of 1mmol, furoyl chloride and the 2ml toluene of 1mmol, the Methyl tanshinonate that adds 0.1mmol at 25 ℃ of stirring reactions after half a hour continued to react 3 hours again, and reaction finishes back CH
2Cl
2Layer is washed 2 times with equal-volume 5% sodium hydrogen carbonate solution earlier with isopyknic washing 3 times again, with washing neutrality, tells organic phase at last; Use anhydrous magnesium sulfate drying, filter, concentrate; Use sherwood oil/acetone=6:1 to carry out rapid column chromatography as eluent, obtain the 1-Cl-Methyl tanshinonate, productive rate is 80%.The 1-Cl-Methyl tanshinonate
1H NMR (
δ, CDCl
3): 7.57 (1H, d), 7.49 (1H, d), 7.24 (1H, q), 6.82 (1H, t), 3.69 (3H, s), 2.54-2.37 (3H, m), 2.28 (3H, m), 1.7 (1H, m), 1.65 (3H, s);
13C NMR (δ, CDCl
3): 183,4,178.6,175.60,161.34,148.69,141.64,143.15,134.91,128. 65,126.63,123.15,121.67,120.21,54.15,52.43,47.2,34.77,33.40,28.57,8.7.
Claims (5)
1. 1-chloro tanshinone compound, it is characterized in that: general structure is:
Wherein, R
1Be to be selected from arbitrarily-CH
3,-OH ,-a kind of among the H,
R
2Be to be selected from arbitrarily-CH
3,-CH
2OH ,-COOCH
3A kind of among the ,-CHO,
R
3Be be selected from arbitrarily-OH ,-a kind of among the H,
R
4Be to be selected from 3-CH arbitrarily
3-furyl, 3-CH
3-2, the 3-2H-furyl ,-CH (CH
3)
2, 3-CH
2A kind of in the OH-furyl.
2. the preparation method of a 1-chloro tanshinone compound is characterized in that: may further comprise the steps: with AlCl
3Put into solvent stirring reaction half a hour with acyl chlorides, add tanshinone compound afterwards again, continued stirring reaction at ambient temperature 3～5 hours, make the 1-Cl-tanshinone compound, the general structure of described tanshinone compound is:
Wherein, R
1Be to be selected from arbitrarily-CH
3,-OH ,-a kind of among the H,
R
2Be to be selected from arbitrarily-CH
3,-CH
2OH ,-COOCH
3A kind of among the ,-CHO,
R
3Be be selected from arbitrarily-OH ,-a kind of among the H,
R
4Be to be selected from 3-CH arbitrarily
3-furyl, 3-CH
3-2, the 3-2H-furyl ,-CH (CH
3)
2, 3-CH
2A kind of in the OH-furyl.
3. the preparation method of 1-chloro tanshinone compound according to claim 2 is characterized in that: described acyl chlorides is a kind of in Benzoyl chloride 99min., furoyl chloride, paranitrobenzoyl chloride, m-nitrobenzoyl chloride, the Acetyl Chloride 98Min..
4. the preparation method of 1-chloro tanshinone compound according to claim 2 is characterized in that: described solvent is methylene dichloride, chloroform, toluene or THF.
5. the preparation method of 1-chloro tanshinone compound according to claim 2 is characterized in that: said AlCl
3, acyl chlorides and tanshinone compound mol ratio be: AlCl
3: acyl chlorides: tanshinone compound=(0.1～10): (0.1～10): 1.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010604829.4A CN102532249B (en) | 2010-12-24 | 2010-12-24 | 1-chloro tanshinone compound and preparation method thereof |
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| CN102532249B CN102532249B (en) | 2015-08-19 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101012270A (en) * | 2007-01-26 | 2007-08-08 | 广东工业大学 | Tanshinone derivative and its application in preparing aldose reduction enzyme inhibitor pharmaceutical |
| CN101070338A (en) * | 2007-06-18 | 2007-11-14 | 刘小虎 | Tanshinone IIA potassium sulfonate for preparing medicine for preventing and treating myocardial ischemia and cerebral ischemia and anoxia |
-
2010
- 2010-12-24 CN CN201010604829.4A patent/CN102532249B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101012270A (en) * | 2007-01-26 | 2007-08-08 | 广东工业大学 | Tanshinone derivative and its application in preparing aldose reduction enzyme inhibitor pharmaceutical |
| CN101070338A (en) * | 2007-06-18 | 2007-11-14 | 刘小虎 | Tanshinone IIA potassium sulfonate for preparing medicine for preventing and treating myocardial ischemia and cerebral ischemia and anoxia |
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| CN102532249B (en) | 2015-08-19 |
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