CN102532249B - 1-chloro tanshinone compound and preparation method thereof - Google Patents
1-chloro tanshinone compound and preparation method thereof Download PDFInfo
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- CN102532249B CN102532249B CN201010604829.4A CN201010604829A CN102532249B CN 102532249 B CN102532249 B CN 102532249B CN 201010604829 A CN201010604829 A CN 201010604829A CN 102532249 B CN102532249 B CN 102532249B
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Abstract
The invention discloses a kind of 1-chloro tanshinone compound, also disclose a kind of preparation method of 1-chloro tanshinone compound, the general structure of 1-chloro tanshinone compound is simultaneously:
Description
Technical field
The invention belongs to pharmaceutical intermediate technical field, be specifically related to 1-chloro tanshinone compound and preparation method thereof.
Background technology
The red sage root be Chun Xing section mouse tail belong to the per nnial herb red sage root (
saiviamiItiorrhizaBunge) dry rhizome.Red sage root bitter, is slightly cold, and enters the heart, pericardium, Liver Channel.In the treatment of Chinese medicine, the red sage root can be used for menoxenia, and through closing dysmenorrhoea, the various pain caused by hemostasis, a lump in the abdomen causing distension and pain, and the swollen and palpitation and insomnia of sore pain etc. are clinical common drug.Modern clinic experiment and pharmacological experiment study confirm that the pharmacological action of the red sage root is mainly reflected in the provide protection to heart, the provide protection to liver, to the provide protection of cerebral tissue, can improves spinal cord microcirculation raising myeloid tissue hypoxia-bearing capability, antitumor action, to the improvement result of blood viscosity, improves renal function effect and to aspects such as the provide protections of skin.The chemical composition of the red sage root can be divided into fat-soluble and water-soluble two portions, fatty contents is based on the diterpene quinone of TANSHINONES type, all containing o-quinone or para-quinoid structure in chemical structure, isolated tens of kinds of tanshinone compounds at present, wherein Tanshinone I, tanshinone IIA, the content of Cryptotanshinone 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, there is multiple pharmacological effect, except there is effect of traditional promoting blood flow to regulate menstruation, stasis-dispelling and pain-killing, tranquilizing by nourishing the heart, anti-oxidant to it, antibacterial, anti-inflammatory, reduction blood viscosity, anticoagulant, promotion fibrinolytic, anticoagulant, prolongation thrombosis and promote thrombolytic effect in recent years, liver protecting, antitumor, conditioner body immunity function and to improve the research of the pharmacological actions such as anti-diabetic microvascular complication also increasingly deep, make tanshinone compound have boundless potential applicability in clinical practice.But because tanshinone compound is fat-soluble component, water insoluble, its bioavailability is in vivo low, so tanshinone compound is carried out structural modification, strengthening it water-soluble, to make various pharmaceutical dosage form, is the optimum method giving full play to tanshinone compound pharmacological action.On tanshinone compound, how to introduce group water-soluble or strengthen its pharmacologically active to strengthen it, thus the pharmaceutical use of tanshinone compound is not fully exerted is the key issue that present tanshinone compound uses.
Summary of the invention
The object of the present invention is to provide a kind of 1-chloro tanshinone compound.
Meanwhile, the present invention also aims to the preparation method that a kind of 1-chloro tanshinone compound is provided.
In order to realize above object, the technical solution adopted in the present invention is: a kind of 1-chloro tanshinone compound, and general structure is:
；
Wherein, R
1be selected from-CH arbitrarily
3, one in-OH ,-H,
R
2be selected from-CH arbitrarily
3,-CH
2oH ,-COOCH
3, one in-CHO,
R
3the one be selected from arbitrarily in-OH ,-H,
R
4be selected from 3-CH arbitrarily
3-furyl, 3-CH
3-2,3-2H-furyls ,-CH (CH
3)
2, 3-CH
2one in OH-furyl.
Described 1-chloro tanshinone compound can be such as any one in 1-Cl-tanshinone IIA, 1-Cl-Cryptotanshinone, 1-Cl-tanshinone ⅡB, 1-Cl-Methyl tanshinonate, 1-Cl-Rosmariquinone, 1-Cl-Tanshindiol A, 1-Cl-3 α-OH-tanshinone IIA, 1-Cl-przewaquinone A, 1-Cl-Radix Salviae Miltiorrhizae C prime, 1-Cl-Radix Salviae Miltiorrhizae D prime, 1-Cl-prezewaquinone E element, 1-Cl-red sage root aldehyde, the different Cryptotanshinone of 1-Cl-IsotanshinoneⅡ A and 1-Cl-.
A preparation method for 1-chloro tanshinone compound, comprises the following steps: by AlCl
3put into solvent stirring reaction half an hour with acyl chlorides, add tanshinone compound more afterwards, continue stirring reaction 3 ~ 5 hours at ambient temperature, obtained 1-Cl-tanshinone compound, the general structure of wherein said tanshinone compound is:
，
Wherein, R
1be selected from-CH arbitrarily
3, one in-OH ,-H,
R
2be selected from-CH arbitrarily
3,-CH
2oH ,-COOCH
3, one in-CHO,
R
3the one be selected from arbitrarily in-OH ,-H,
R
4be selected from 3-CH arbitrarily
3-furyl, 3-CH
3-2,3-2H-furyls ,-CH (CH
3)
2, 3-CH
2one in OH-furyl.
Described acyl chlorides is the one in Benzoyl chloride, furoyl chloride, paranitrobenzoyl chloride, m-nitrobenzoyl chloride, Acetyl Chloride 98Min..
Described solvent is methylene dichloride, chloroform, toluene or tetrahydrofuran (THF).
Described 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 is obtained by 1 introducing chlorine atom at tanshinone compound, easily there is chemical reaction in 1-chloro tanshinone compound obtained after chloro, other products can be converted into very easily, the problem that tanshinone compound for unique molecular structure is difficult to carry out structural modification provide a kind of can the solution of reference, also provide a kind of new approach for the pharmaceutical use of tanshinone compound obtains exploitation fully 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 good prospects for commercial application.
Embodiment
Embodiment 1
1-Cl-tanshinone IIA, structural formula is:
。
The preparation method of 1-Cl-tanshinone IIA: the methylene dichloride adding the aluminum chloride of 0.3mmol, the Benzoyl chloride of 0.3mmol and 2ml in there-necked flask, the tanshinone IIA of 0.1mmol is added after 25 DEG C of stirring reaction half an hour, continue stirring reaction again 3 hours, reaction terminates rear CH
2cl
2layer first with isopyknic washing 3 times, then washes 2 times with equal-volume 5% sodium hydrogen carbonate solution, finally washes neutrality with water, separates organic phase, with anhydrous magnesium sulfate drying, filter, concentrated, be that eluent carries out rapid column chromatography with sherwood oil/acetone=8:1, obtain 1-Cl-tanshinone IIA, productive rate is 75%.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
1-Cl-Cryptotanshinone, structural formula is:
。
The preparation method of 1-Cl-Cryptotanshinone: add the aluminum chloride of 0.1mmol, the m-nitrobenzoyl chloride of 0.1mmol and 2ml chloroform in there-necked flask, 25 DEG C of stirring reaction half an hour, the Cryptotanshinone adding 1mmol afterwards continues reaction 5 hours again, and reaction terminates rear CH
2cl
2layer first with isopyknic washing 3 times, then washes 2 times with equal-volume 5% sodium hydrogen carbonate solution, finally washes neutrality with water, separates organic phase, with anhydrous magnesium sulfate drying, filter, concentrated, be that eluent carries out rapid column chromatography with sherwood oil/acetone=8:1, obtain 1-Cl-Cryptotanshinone, productive rate is 80%.1-Cl-Cryptotanshinone
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
1-Cl-Methyl tanshinonate, structural formula is:
。
The preparation method of 1-Cl-Methyl tanshinonate: add the aluminum chloride of 1mmol, the furoyl chloride of 1mmol and 2ml toluene in there-necked flask, the Methyl tanshinonate adding 0.1mmol after 25 DEG C of stirring reaction half an hour continues reaction 3 hours again, and reaction terminates rear CH
2cl
2layer first with isopyknic washing 3 times, then washes 2 times with equal-volume 5% sodium hydrogen carbonate solution, finally washes neutrality with water, separates organic phase, with anhydrous magnesium sulfate drying, filter, concentrated, be that eluent carries out rapid column chromatography with sherwood oil/acetone=6:1, obtain 1-Cl-Methyl tanshinonate, productive rate is 80%.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. a 1-chloro tanshinone compound, is characterized in that: general structure is:
Wherein, R
1be selected from-CH arbitrarily
3, one in-OH ,-H,
R
2be selected from-CH arbitrarily
3,-COOCH
3, in one,
R
3the one be selected from arbitrarily in-OH ,-H,
R
4be selected from 3-CH arbitrarily
3-furyl, 3-CH
3one in-2,3-2H-furyls.
2. a preparation method for 1-chloro tanshinone compound, is characterized in that: comprise the following steps: by AlCl
3put into solvent stirring reaction half an hour with acyl chlorides, add tanshinone compound more afterwards, continue stirring reaction 3 ~ 5 hours at ambient temperature, obtained 1-Cl-tanshinone compound, the general structure of described tanshinone compound is:
Wherein, R
1be selected from-CH arbitrarily
3, one in-OH ,-H,
R
2be selected from-CH arbitrarily
3,-COOCH
3, in one,
R
3the one be selected from arbitrarily in-OH ,-H,
R
4be selected from 3-CH arbitrarily
3-furyl, 3-CH
3one in-2,3-2H-furyls.
3. the preparation method of 1-chloro tanshinone compound according to claim 2, is characterized in that: described acyl chlorides is the one in Benzoyl chloride, furoyl chloride, paranitrobenzoyl chloride, m-nitrobenzoyl chloride, 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 tetrahydrofuran (THF).
5. the preparation method of 1-chloro tanshinone compound according to claim 2, is characterized in that: described 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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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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