CN1010777B - The preparation method of xanthone derivative - Google Patents
The preparation method of xanthone derivativeInfo
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- CN1010777B CN1010777B CN89102374A CN85107319A CN1010777B CN 1010777 B CN1010777 B CN 1010777B CN 89102374 A CN89102374 A CN 89102374A CN 85107319 A CN85107319 A CN 85107319A CN 1010777 B CN1010777 B CN 1010777B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/84—Xanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
- C07D311/86—Oxygen atoms, e.g. xanthones
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
- Y02A40/10—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in agriculture
- Y02A40/20—Fertilizers of biological origin, e.g. guano or fertilizers made from animal corpses
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the xanthone derivative of general formula (I) representative,
(W, Z, Y in the general formula, A and B are defined in the specification) reaches the preparation method of the non-toxic salt of this derivative when B is oh group.
The compound of general formula of the present invention (I) can be used as to have uricosuric and urinates active diuretic(s), also can be used for treating edema and hypertension.
Description
(Y and Z can be the same or different, and represent hydrogen atom for W wherein, X, halogen atom or have the low-grade alkyl group of 1 to 4 carbon atom; A is a hydrogen atom, or combines the methene chain that generates ring texture with X or Y; B is a methylol groups, elementary alkoxycarbonyl group with 1-4 carbon atom, or carboxylic group, work as X, Y and Z respectively are hydrogen atoms, and A is a hydrogen atom simultaneously, when B is carboxylic group or elementary alkoxycarbonyl group, W is not hydrogen atom or 7-position methyl group), and non-toxic salt (when B is carboxylic group).
The compound of the logical formula I of the present invention can be used as to have uricosuric and urinates active diuretic(s) and also can be used for treating edema or hypertension.
To urinate active known diuretic(s) be to be the phenoxy acetic acid class (United States Patent (USP) 3758506) of typical case representative with the thenoic acid similar in appearance to the uricosuric that has of The compounds of this invention.
General diuretic antihypertensive preparation at first all is used for treating hypertension as medicine the time, but as pay reaction they be easy to cause uricemia.In addition, hyperuricemia is aggravated hypertension through regular meeting, and it is believed that most of hyperuricemia is that disorder owing to uric acid excretion causes.In the case, the pharmaceutical field development of being eager has uricosuric and urinates active diuretic(s).As mentioned above, known thenoic acid is to have uricosuric to urinate active a kind of possible diuretic(s), but its not commercialization as yet, this is because as the effect of paying, it produces disease of the liver possibly.
Carried out different research and overcome above-mentioned shortcoming, we have found that the xanthone derivative of logical formula I has uricosuric urine activity and has diuretic activity again, and very little to the effect of paying of liver.According to this discovery, we have finished the present invention.
According to the present invention, the xanthone derivative of logical formula I can be divided into the compound of logical formula II and furo xanthone (furoxanthones) compound of logical formula III particularly.
In (in II), W, X, Y, the definition of Z and B is worked as X with logical formula I, Y, Z respectively are hydrogen atoms, not hydrogen atom and 7-position methyl group of W then when B is carboxylic group or elementary alkoxycarbonyl group);
(wherein W, X, Y and B are as defined above).
At logical formula I, in the xanthene derivative of (II) and (III), halogen atom is a fluorine, and chlorine, bromine or iodine, low-grade alkyl group are the straight or branched alkyl groups with 1～4 carbon atom.When B was carboxylic group, derivative can generate salt with alkali.These salt can be basic metal, and alkaline earth salt replaces or unsubstituted amine salt.The concrete example of these salt is sodium salt, calcium salt, magnesium salts, ammonium salt, low-grade alkylamine salt and ethanolamine salt.Available usual method makes these salt at an easy rate.
The compound of the logical formula I of the present invention is a new compound.The compound of available logical formula IV and general formula L-CH
2The compound of-B reacts and prepares logical formula II
(Y and Z are as above-mentioned definition, at formula 1-cH for W in the formula IV, X
2Among-the B, B as defined above, L is a halogen atom, oh group or as the acyl-oxygen group of leavings group).
Preferentially select for use in inert solvent, in the presence of alkali, react.The example of inert solvent comprises: ether, alcohol, hydrocarbon, aromatic hydrocarbon, and water, sprotic polar solvent has N, dinethylformamide, and dimethyl alum.The example of alkali is alkali-metal hydride, alkali alcoholate, alkali-metal oxyhydroxide and alkali-metal carbonate and organic bases.Example comprises sodium hydride more specifically, sodium methylate, sodium ethylate, sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood and triethylamine.Temperature of reaction is selected for use from 0 ℃ to 150 ℃.
The also available corresponding compounds of xanthone derivative (wherein B is a carboxylic group) (wherein B is an elementary alkoxycarbonyl group) of logical formula II prepares with general method, and for example the method with the alkaline hydrated oxide hydrolysis prepares.
The concrete example of furo xanthone derivative of the logical formula II of the present invention is: 5-oxygen-5H-furo (3,2-b) xanthone and 6-oxygen-6H-furo (2,3-C) xanthone.(III a) compound belongs to The compounds of this invention to the general formula of following formula representative.
(wherein X, Y and W are as defined above), they can react by the compound of acid and general formula (V) and prepare:
(X wherein, the definition of Y and W is the same, as long as hydroxyl and 2-propenyl are substituted at its vicinal.
With general formula (III compound a) obtains the compound of the general formula (III b) of the scope of the invention:
(wherein X, the definition of Y and W is the same).
The available general method of compound (wherein B is an elementary alkoxycarbonyl group) of logical formula III, the compound by esterification general formula (III b) prepares.At inert solvent, for example react in ether or the hydrocarbon.Temperature of reaction can suitably be selected between 0 ℃～250 ℃.By general formula (V) compound general formula (a) in the process of compound, used organic peracid is a peracetic acid to III, perbenzoic acid ,-chloro-benzoic acid.Can adopt usual method with general formula (III a) hydrogenation of compounds and change into the compound of general formula (III b), for example use manganese, the oxide compound of chromium or the like.Corresponding 2-propenyl aryl oxide can be carried out the compound that Claisen rearrangement prepares general formula (V).
The pharmacologically active of compound
The compounds of this invention diuresis and uricosuric urine activity are proved by following test.
Method:
With Wistar-Imamicki rat (7 week) grouping that was hungry 24 hours, 4 or 5 every group, the urine amount that every treated animal is discharged about equally.Force urinate after, give the test compound of rat oral suspension in the physiological saline that contains 3% gum arabic, taking dose is 25 milliliters of pers kilogram of body weight.Typical suspension taking dose is 100 milligrams/kilogram.Control rats is only taken the physiological saline that contains 3% gum arabic.The animal of test usefulness is closed in independent metabolic cage, make its complete hunger after, collect the urine of every rat after 6 hours taking test compound or physiological saline.Urine is entered the volume that the measurement tube can directly be read urine, calculate the urine amount of per kilogram of body weight.With the uric acid amount in uriKoxidase-hydrogen peroxide enzyme process mensuration urine.
The result:
Can find out that from following table The compounds of this invention has good diuresis and uricosuric urine is active, its activity is directly proportional with dosage and is long lasting.Compound number in the table be with specification sheets thereafter in embodiment number corresponding.
Table 1
Experimental compound urine amount % uric acid amount %
Milliliter/kilogram milliliter/kilogram
Contrast 17.7 ± 3.9 100 3.44 ± 0.57 100
Compound 13 35.4 ± 7.6 199.5c 5.11 ± 1.00 148.6
Control group 16.7 ± 6.9 100 3.05 ± 0.48 100
Compound 21 31.8 ± 6.6 190.8c 3.86 ± 0.61 126.3
Control group 14.7 ± 1.8 100 2.38 ± 0.23 100
Compound 23 369 ± 3.3 250.3c 3.13 ± 0.22 131.7
Control group 1.81 ± 2.1 100 3.43 ± 0.20 100
Compound 35 49.7 ± 2.0 275.0c 4.30 ± 0.22 125.29
a：p＜0.05 b：p＜0.01 c：p＜0.001
The following examples further specify claimed compounds, but do not limit the present invention.
Embodiment 1
With 2.6 gram 4-chloro-, 8 fluoro-3-carboxyls-9-oxygen-9H-xanthene, 2.8 gram salt of wormwood, 3,3 gram ethyl bromoacetate and 40 milliliters of N, the mixture of dinethylformamide (DMF) stirred 4 hours at 60～70 ℃.Add entry behind the cooling mixture in it, the crystallization that filtered and recycled generated washes with water, and dry.Use alcohol crystal, obtain 3.4 gram 4-chloro-8-fluoro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid ethyl esters.With this ester (3.3 gram), the sodium hydroxide (1.9 gram) and the mixture of water (00 milliliter) refluxed 30 minutes.Cooling mixture is used the concentrated hydrochloric acid acidifying, the crystallization that filtered and recycled generated, and dry, use N, the dinethylformamide recrystallization obtains 2.5 gram 4-chloro-8-fluoro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid, 300 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e322.
Embodiment 2
With 1.2 gram 4-chloro-3-carboxyl-9-oxygen-9H-xanthenes, 1.7 gram salt of wormwood, 2.1 gram ethyl bromoacetate and 30 milliliters of N, the mixture of dinethylformamide stirred 3 hours at 60～70 ℃.Add entry behind the cooling mixture in it, the crystallization that filtered and recycled generated washes with water, and dry.Use alcohol crystal, obtain 1.1 gram 4-chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid ethyl esters.183～185 ℃ of fusing points.
With this ester (0.9 gram), the sodium hydroxide (0.7 gram) and the mixture of water (40 milliliters) refluxed 1 hour.After the cooling, use the concentrated hydrochloric acid acidifying, the filtered and recycled solid crystal washes with water and drying, uses ethyl alcohol recrystallization, obtains 0.7 gram 4-chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid, fusing point 280-281 ℃
The mass spectrum molecular ion peak of this compound is m/e304.
Embodiment 3
With 1.0 gram 3-carboxyl-4-methyl-9-oxygen-9H-xanthenes, 1.5 gram salt of wormwood, 1.8 gram ethyl bromoacetate and 20 milliliters of N, the mixture of dinethylformamide stirred 2 hours at 60～70 ℃.Mixture cooling back is added 2 gram potassium hydroxide and 40 ml waters in it, the gained mixture was stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, a filtered and recycled solid crystal washes with water and drying.Obtain 1.0 gram 4-methyl-9-oxygen-9H-xanthene-3-base-fluoroacetic acid with ethyl alcohol recrystallization.244～247 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e284.
Embodiment 4
With 108 gram 8-chloro-3-hydroxyl-9-oxygen-9H-xanthene 3.2 gram salt of wormwood, 3.7 gram ethyl bromoacetate and 100 milliliters of N, the mixture of dinethylformamide stirred 4 hours at 60～70 ℃.Cooling mixture adds 5 milligrams of sodium hydroxide and 100 ml waters, and the mixture that is generated was stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying, uses ethyl alcohol recrystallization, obtains 2.0 gram 8-fluoro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.180～183 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e288.
Embodiment 5
With 1.5 gram 8-fluoro-3-hydroxy-4-methyl-9-oxygen-9H-xanthenes, 3.0 gram salt of wormwood, 3.6 gram ethyl bromoacetate and 40 milliliters of N, the mixture of dinethylformamide stirred 2 hours at 60～70 ℃.Cooling mixture adds 3 gram sodium hydroxide and 40 ml waters, at 90～100 ℃ the mixture that is generated is stirred 30 minutes.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes drying with water, uses N, and N-diformamide recrystallization obtains 1.4 gram 8-fluoro-4-methyl-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.259～261 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e302.
Embodiment 6
With 1.3 gram 2-chloro-8-fluoro-3-hydroxyl-9-oxygen-9H-xanthenes, 1.7 gram salt of wormwood, 2.1 gram ethyl bromoacetate and 30 milliliters of N, the mixture of dinethylformamide stirred 3 hours at 60～65 ℃.Cooling mixture adds 2 gram sodium hydroxide and 100 ml waters, and the mixture that generates was stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying, uses N, and N dimethylformamide recrystallization obtains 1.0 gram 2-chloro-8-fluoro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.239～242 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e322.
Embodiment 7
With 2.6 gram 3-chloro-8-fluoro-2-hydroxyl-9-oxygen-9H-xanthenes, 3.4 gram salt of wormwood, 4.2 gram ethyl bromoacetate and 60 milliliters of N, the mixture of dinethylformamide stirred 5 hours at 60～65 ℃.Behind the cooling mixture, add 4 gram sodium hydroxide and 100 ml waters, the mixture that obtains was stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying, uses ethyl alcohol recrystallization, obtains 1.2 gram 3-chloro-8-fluoro-9-oxygen-9H-xanthene-2-base-fluoroacetic acid.242～245 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e322.
Embodiment 8
With 4,8-two chloro-3-hydroxyls-9-oxygen-9H-xanthene (2.8 gram) salt of wormwood (3.4 gram) ethyl bromoacetate (4.2 gram) N, the mixture of dinethylformamide (60 milliliters) stirred 6.5 hours at 60～65 ℃.Add sodium hydroxide 4 gram and water (100 milliliters) behind the cooling mixture, the filtered and recycled solid crystal washes with water and drying, uses N, and the dinethylformamide recrystallization obtains 2.4 grams 4,8-two chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.270～271 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e338.
Embodiment 9
With 4,6-two chloro-3-hydroxyls-9-oxygen-9H-xanthene (2.0 gram) salt of wormwood (3.4 gram) ethyl bromoacetate (4.2 gram) and N, the mixture of dinethylformamide (60 milliliters) stirred 4 hours at 60～65 ℃.Add sodium hydroxide (4 gram) and water (100 milliliters) behind the cooling mixture, in the mixture of 90～100 stirring gained 30 minutes.The hcl acidifying mixture is used in the cooling back, and the filtered and recycled solid crystal washes with water and drying.Use N, N-dimethyl formyl recrystallization obtains 1.5 grams 4,6-two chloro-9-oxygen-9H-anthracene-3-base-fluoroacetic acid of mixing.270 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e338.
Embodiment 10
With 4-bromo-8-fluoro-2-hydroxyl-9-oxygen-9H-xanthene (1.5 gram) salt of wormwood (3.4 gram) ethyl bromoacetate (4.2 gram) and N, the mixture of dinethylformamide (60 milliliters) stirred 4 hours at 60～65 ℃.Add sodium hydroxide (2 gram) and water (100 milliliters) behind the cooling mixture, in the mixture of 90～100 ℃ of stirring gained 30 minutes.The hcl acidifying mixture is used in the cooling back, and the filtered and recycled solid crystal washes with water and drying, uses ethyl alcohol recrystallization, obtains the assorted anthracene of 1.2 gram 4-bromo-8-fluoro-9-oxygen-9H--2-base-fluoroacetic acid.220～223 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e366.
Embodiment 11
With 4,7-two chloro-3-hydroxyls-9-oxygen-9H-xanthene (2.0 gram) salt of wormwood (3.4 gram) ethyl bromoacetate (4.2 gram) and N, the mixture of dinethylformamide (60 milliliters) stirred 4 hours at 60～65 ℃.Add sodium hydroxide (4 gram) and water (100 milliliters) behind the cooling mixture, the gained mixture was stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes drying with water.Use N, the dinethylformamide recrystallization obtains 1.3 gram 4.7-, two chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.262～263 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e338.
Embodiment 12
With 4,5-two chloro-3-hydroxyls-9-oxygen-9H-xanthene (2.0 gram) salt of wormwood (3.4 gram) ethyl bromoacetate (4.2 gram) and N, the mixture of dinethylformamide (60 milliliters) stirred 4 hours at 60～65 ℃.Add sodium hydroxide (4 gram) and water (100 milliliters) behind the cooling mixture, the mixture that obtains stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use N, the dinethylformamide recrystallization obtains 1.5 gram 4.5-, two chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.283～286 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e338.
Embodiment 13
Under ice-cooled and stirring 11 gram aluminum chloride are joined diphenol dimethyl ether between 4-chlorine (14.2 gram) gradually, 2-fluorobenzoyl chloride (13.0 gram) and 1 is in the mixture of 2-ethylene dichloride (200 milliliters).At room temperature continuously stirring is 2 hours.Reflux after 1 hour, mixture is injected in the water, use the ether extraction mixture.Wash with water also and boil off solvent after the drying.Sodium methylate (in methyl alcohol) and 300 milliliters of ethanol of adding 32 grams 28%, backflow mixture 1 hour.Add 200 ml waters behind the cooling mixture, the filtered and recycled solid crystal washes with water and drying.Resulting crystallization is added in the hot pyridine hydrochloric acid (185～195 ℃), stirs 2 hours (in said temperature).Add entry behind the cooling mixture, the filtered and recycled solid crystal washes with water and drying.The crystallization that generates is added to salt of wormwood (22.6 gram), and ethyl bromoacetate (27.4 gram) and N in the mixture of N-dimethylformamide (400 milliliters), stir the gained mixture 2 hours at 65～75 ℃.Behind the cooling mixture, add sodium hydroxide (40 gram) and water (400 milliliters), the gained mixture was stirred 1 hour at 90～100 ℃.The hcl acidifying mixture is used in the cooling back, and the filtered and recycled solid crystal washes with water and drying.Use N, the dinethylformamide recrystallization obtains 2-chlorine 9-oxygen-9H-xanthene-3-base-fluoroacetic acid.248～249 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e304.
Embodiment 14
With 3-chloro-2-hydroxyl-9-oxygen-9H-xanthene (1.5 gram) salt of wormwood (2.5 gram) ethyl bromoacetate (3.1 gram) and N, the mixture of dinethylformamide (40 milliliters) stirred 2 hours at 65～75 ℃.Add sodium hydroxide (4 gram) and water (100 milliliters) behind the cooling mixture, the mixture that is generated stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.5 gram 3-chloro-9-oxygen-9H-xanthene-2-base-fluoroacetic acid.237～238 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e304.
Embodiment 15
With 4-bromo-2-hydroxyl-9-oxygen-9H-xanthene (2.0 gram), salt of wormwood (1.9 gram) ethyl bromoacetate (2.3 gram) and N, the mixture of dinethylformamide (20 milliliters) stirred 1.5 hours at 60～70 ℃.Add sodium hydroxide (4 gram) and water (40 milliliters) behind the cooling mixture, the gained mixture stirred 30 minutes at 90～100 ℃.After the cooling, use the hydrochloric acid treating mixture, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.8 gram 4-bromo-9-oxygen-9H-xanthene-2-base-fluoroacetic acid.219～221 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e348.
Embodiment 16
With 1-chloro-3-hydroxyl-9-oxygen-9H-xanthene (1.0 gram) salt of wormwood (1.1 gram), ethyl bromoacetate (1.4) and N, the mixture of dinethylformamide (20 milliliters) stirred 5 hours at 60～70 ℃.Cooling mixture added sodium hydroxide (2 gram) and water (50 milliliters), in 90～100 ℃ of mixtures that stir generations 30 minutes.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 0.8 gram 1-chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.231～233 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e304.
Embodiment 17
With 1,2-two chloro-3-hydroxyls-9-oxygen-9H-xanthene (2.0 gram) salt of wormwood (2.0 gram) ethyl bromoacetate (2.4 gram) and N, the mixture of dinethylformamide (40 milliliters) stirred 1.5 hours at 60～70 ℃.Behind the cooling mixture, add sodium hydroxide (2 gram) and water (100 milliliters), the mixture that obtains was stirred 30 minutes at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use N, the dinethylformamide recrystallization obtains 1.7 grams 1,2-two chloro-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.288～290 ℃ of fusing points.The mass spectrum molecular ion peak of this compound is m/e338.
Embodiment 18
With 2-hydroxy-3-methyl-9-oxygen-9H-xanthene (1.1 gram), salt of wormwood (1.4 gram) ethyl bromoacetate (1.7 gram) and N, the mixture of dinethylformamide (20 milliliters) stirred 3 hours at 60～70 ℃.Behind the cooling mixture, add sodium hydroxide (4 gram) and water (100 milliliters), the gained mixture stirred 1 hour at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use N, the dinethylformamide recrystallization obtains 1.3 gram 3-methyl-9-oxygen-9H-xanthene-2-base-fluoroacetic acid.225～227 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e284.
Embodiment 19
With 3-hydroxyl-1-methyl-9-oxygen-9H-xanthene (5.0 gram), salt of wormwood (6.0 gram), ethyl bromoacetate (7.0 gram) and N, dinethylformamide (100 milliliters) stirred 5 hours at 60～70 ℃.Behind the cooling mixture, add sodium hydroxide (10 gram) and water (200 milliliters), the gained mixture stirred 1 hour at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 5.0 gram 1-methyl-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.189～190 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e284.
Embodiment 20
With 2-chloro-3-hydroxyl-1-methyl-9-oxygen-9H-xanthene (1.3 gram), salt of wormwood (1.4 gram), ethyl bromoacetate (1.7 gram) and N, the mixture of dinethylformamide (20 milliliters) stirred 5 hours at 60～70 ℃.Cooling mixture adds sodium hydroxide (4 gram) and water (100 milliliters), and the gained mixture stirred 1 hour at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use N, the dinethylformamide recrystallization obtains 0.9 gram 2-chloro-1-methyl-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.275～278 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e318.
Embodiment 21
With 2-bromo-3-hydroxyl-1-methyl-9-oxygen-9H-xanthene (5.0 gram) salt of wormwood (7.1 gram) ethyl bromoacetate (8.6 gram) and N, the mixture of dinethylformamide (80 milliliters) stirred 5 hours at 55～65 ℃.Behind the cooling mixture, add sodium hydroxide (10 gram), water (250 milliliters) stirs the gained mixture 2 hours at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 3.0 gram 2-bromo-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.227～230 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at me/348.
Embodiment 22
With 2,4-two chloro-3-hydroxyls-9-oxygen-9H-xanthene (7.5 gram), salt of wormwood (7.5 gram) ethyl bromoacetate (9.0 gram) and N, the mixture of dinethylformamide (100 milliliters) stirred 3 hours at 55～65 ℃.Behind the cooling mixture, add sodium hydroxide (20 gram), water (250 milliliters) stirs the gained mixture 1 hour at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Obtain 4.0 grams 2,4-two chloro-9-oxygen 9H-xanthene-3-base-fluoroacetic acid with ethyl alcohol recrystallization.225～228 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e338.
Embodiment 23
With 3-hydroxy-2-methyl-9-oxygen-9H-xanthene (1.8 gram), salt of wormwood (2.2 gram) ethyl bromoacetate (2.7 gram) and N, the mixture of dinethylformamide (40 milliliters) stirred 2 hours at 60～70 ℃.Behind the cooling mixture, add sodium hydroxide (3.2 gram), and water (40 milliliters), the gained mixture stirred 1 hour at 90～100 ℃.After the cooling, use the hcl acidifying mixture, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.8 gram 2-methyl-9-oxygen-9H-xanthene-3-base-fluoroacetic acid.236～238 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e284.
Embodiment 24
With 2-chloro-3-hydroxyl-9-oxygen-9H-xanthene (8.0 gram) salt of wormwood (13 gram), ethylene bromohyrin (12 gram) and N, the mixture of dinethylformamide (200 milliliters) stirred 3 hours at 45～55 ℃.After solvent is fallen in vacuum-evaporation, add water in residuum, the filtered and recycled solid crystal washes with water and drying.Use N, the mixture recrystallization of dinethylformamide and water obtains the 6.0 2-chloro-3-(2-hydroxy ethoxies that restrain)-9-oxygen-9H-xanthene.153～156 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e290.
Embodiment 25
With between 9.5 grams-the chloro-peroxybenzoic acid joins in the mixture of 2-propenyl-3-hydroxy-4-methyl-9-oxygen-9H-xanthene (11 gram) and chloroform (800 milliliters), in room temperature with the mixture stirring of gained 5 hours, standing over night then.Add salt of wormwood (20 gram) and water (500 milliliters) in mixture, use the chloroform extraction mixture.Dry chloroform layer boils off solvent.Use ethyl alcohol recrystallization, obtain 10 grams 2,3-dihydro-2-methylol-11-methyl-5-oxygen-5H-furo (3,2-b) xanthene.Fusing point 242-243 ℃.The mass spectrum of this compound has a part quasi-molecular ions at m/e282.
Embodiment 26
Under agitation, with chromium trioxide (57 gram), the mixture of the water (280 milliliters) and the vitriol oil (84 gram) be added dropwise to that method with embodiment 25 makes 2,3-dihydro-2-methylol-11-methyl-5-oxygen-5H-furo (2,3-b) in the mixture of xanthene (16.1 gram) and acetone (3000 milliliters), with gained mixture standing over night and filtration.The filtrate vaporising under vacuum is to doing.Add the entry after-filtration and reclaim solid crystal, wash with water and drying.With the admixture solvent recrystallization of methyl alcohol and methylene dichloride, obtain 11.1 grams 2,3-dihydro-11-methyl-5-oxygen-5H-furo (3,2b) xanthene-2-carboxylic acid.297～299 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e296.
Embodiment 27
With between 4-propenyl-8-fluoro-3-hydroxyl-9-oxygen-9H-xanthene (14 gram)-oxygen peroxybenzoic acid (1.2 gram) and the mixture of chloroform (250 milliliters) at room temperature stirred 5 hours, standing over night then.After adding salt of wormwood (2 gram) and water (50 milliliters), use the chloroform extraction mixture, dry chloroform phase, solvent evaporated.Use the ethyl alcohol recrystallization residuum, get 1.2 gram 7-chloro-1,2-two chloro-2-methylols-6-oxygen-6H-furo (2,3-c) xanthene.220～221 ℃ of fusing points, the mass spectrum of this compound has a part quasi-molecular ions at m/e286.
Embodiment 28
Under agitation condition with chromium trioxide (14 gram), the water (80 milliliters) and the vitriol oil (24 gram) are added dropwise to implement the 8.0 gram 7-fluoro-1 that 27 method makes, in the ice-cold mixture of 2-dihydro-2-methylol-6-oxygen-6H-furo (2,3-c) xanthene and 1000 milliliters of acetone.Mixture standing over night after-filtration with gained.Under vacuum, filtrate is evaporated to dried.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use N, the dinethylformamide recrystallization obtains 8.1 gram 7-chloro-1,2-dihydro-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acid.262～265 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e300.
Embodiment 29
With 2-propenyl-8-chloro-3-hydroxy-4-methyl-9-oxygen-9H-xanthene (9.0 gram) ,-chlorine peroxybenzoic acid (8.0 gram) and the mixture of chloroform (1000 milliliters) at room temperature stirred 5 hours, standing over night then.With salt of wormwood (20 gram), water adds in the mixture for 500 milliliters, with chloroform extraction gained mixture, dry chloroform layer, solvent evaporated.Residuum is dissolved in acetone (1000 milliliters), stirs this solution, and at room temperature be added dropwise to chromium trioxide (21 gram), the mixture of the water (120 milliliters) and the vitriol oil (36 gram), after the standing over night, filtering mixt is evaporated to filtrate dried under vacuum.Add entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 5.0 gram 6-fluoro-2,3-dihydro-11-methyl-5-oxygen-5H-furo (3,2-b) xanthene-2-carboxylic acid.Fusing point 292-295 ℃, the mass spectrum of this compound has a part quasi-molecular ions at m/e314.
Embodiment 30
With 4-propenyl-8-chloro-3-hydroxyl-9-oxygen-9H-xanthene (15 gram) ,-chlorine peroxybenzoic acid (14 gram) and the mixture of chloroform (1000 milliliters) at room temperature stirred 5 hours, standing over night then.Salt of wormwood (20 gram) and water (500 milliliters) are added in the mixture, with chloroform extraction gained mixture.Dry chloroform layer, solvent evaporated.Residuum is dissolved in (2000 milliliters) in the acetone, stirs this solution, at room temperature with chromium trioxide (15 gram), the water (90 milliliters) and the mixture of the vitriol oil are added dropwise in it.Standing over night, filtering mixt under the vacuum is evaporated to filtrate dried.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 8.0 gram 7-chloro-1,2-dihydro-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acid.283～286 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e316.
Embodiment 31
With 2-propenyl-4,8-2 chloro-3-hydroxyl-9-oxygen-9H-xanthene (14 gram) ,-chlorine peroxybenzoic acid (11 gram) and the mixture of chloroform (1000 milliliters) at room temperature stirred 5 hours, standing over night then.Salt of wormwood (20 gram) and water (500 milliliters) are added in the mixture with chloroform extraction gained mixture.Dry chloroform layer, solvent evaporated.Residuum is dissolved in (2000 milliliters) in the acetone, stirs this mixed solution, at room temperature with chromium trioxide (17 gram), water (100 milliliters), and the vitriol oil (30 gram) is added dropwise to this mixture.Standing over night after-filtration mixture under the vacuum is evaporated to filtrate dried.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 5.0 grams 6,11-2,3-dihydro-5 oxygen-5 hydrogen-furo (2,3-b) xanthene-2-carboxylic acid.291～294 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e350.
Embodiment 32
With 4-propenyl-3-hydroxyl-9-oxygen-9H-xanthene (10 gram) ,-chlorine peroxybenzoic acid (21 gram) and the mixture of chloroform (1000 milliliters) at room temperature stirred 5 hours, standing over night then.Salt of wormwood (40 gram) and water (1000 milliliters) are added in it, with chloroform extraction gained mixture.Dry chloroform layer, and be evaporated to dried.Residuum is dissolved in acetone (2000 milliliters), stirs this solution, at room temperature with chromium trioxide (9 gram), the mixture of the water (40 milliliters) and the vitriol oil (15 gram) is added dropwise in it.After the standing over night, filtering mixt is evaporated to filtrate dried under vacuum.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 4 grams 1,2-dihydro-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acid.283～286 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e282.
Embodiment 33
With 2-propenyl-4-chloro-3-hydroxyl-9-oxygen-9H-xanthene (2.0 gram) ,-chlorine peroxybenzoic acid (3.6 gram), and the mixture of chloroform (100 milliliters) at room temperature stirred 5 hours, then standing over night.Salt of wormwood (8 gram) and water (200 milliliters) are added in the mixture, use the chloroform extraction mixture.Dry chloroform layer, and steam solvent.Residuum is dissolved in acetone (400 milliliters), and at room temperature with chromium trioxide (1.7 gram), the water (10 milliliters) and the vitriol oil (3 gram) are added dropwise in the solution that is stirring.After the standing over night, under reduced pressure filtrate is evaporated to dried.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain the 11-chloro-2 of 0.9 gram, 3-dihydro-5-oxygen-5H-furo (2,3-b) xanthene-2-carboxylic acid.290～293 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e316.
Embodiment 34
With 2-propenyl-4-chloro-8-fluoro-3-hydroxyl-9-oxygen-9H-xanthene (2.8 gram) ,-chlorine peroxybenzoic acid (4.7 gram) and the mixture of chloroform (100 milliliters) at room temperature stirred 5 hours, standing over night then.Salt of wormwood (10 gram) and water (200 milliliters) are added in the mixture, use the chloroform extraction mixture.Dry chloroform layer, and steam solvent.With acetone (500 milliliters) dissolving residuum, at room temperature with chromium trioxide (2.8 gram), the water (16 milliliters) and the vitriol oil (4.8 gram) are added in the solution that is stirring.After the standing over night, filtering mixt is evaporated to filtrate dried under vacuum.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain the 11-chloro-6-fluoro-2 of 1.0 grams, 3-dihydro-5-oxygen-5H-furo (2,3-b) xanthene-2-carboxylic acid.300 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e334.
Embodiment 35
With 4-propenyl-2-chloro-3-hydroxyl-9-oxygen-9H-xanthene (2.9 gram) ,-chlorine peroxybenzoic acid (3.5 gram), and the mixture of chloroform (300 milliliters) at room temperature stirred 5 hours, then standing over night.In mixture, add salt of wormwood (10 gram), and water (200 milliliters), with the resulting mixture of chloroform extraction.Dry chloroform layer, solvent evaporated.4-chloro-1,2 dihydro-2 methylols-6-oxygen-6H-furo (2, the 3-c) xanthene that obtains is dissolved in the acetone (300 milliliters), at room temperature, with chromium trioxide (3.3 gram), water 17(milliliter), and the mixture of the vitriol oil (5 gram) is added in the mixture solution that is stirring.After the standing over night, Virahol (10 milliliters) is joined in the mixture, filter the mixture that is generated, filtrate vacuum-evaporation is extremely done.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.7 gram 4-chloro-1,2-dihydro-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acid.292～295 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e316.
Embodiment 36
With 4-propenyl-1-chloro-3-hydroxyl-9-oxygen-9H-xanthene (3.0 gram) ,-chlorine peroxybenzoic acid (7.2 gram) and the mixture of chloroform (500 milliliters) at room temperature stirred 5 hours, standing over night then.In mixture, add salt of wormwood (20 gram) and water (400 milliliters), with the resulting mixture of chloroform extraction.Dry chloroform layer, solvent evaporated.With acetone (300 milliliters) dissolving residuum, stir this solution, at room temperature be added dropwise to chromium trioxide (3.3 gram), the mixture of the water (17 milliliters) and the vitriol oil (5 gram), after the standing over night, filtering mixt is extremely done filtrate vacuum-evaporation.Add the entry after-filtration and reclaim solid crystal, wash with water and drying.Use ethyl alcohol recrystallization, obtain 1.6 gram 5-chloro-1,2-dihydro-6-oxygen-6H-furo (2,3-b) xanthene-2-carboxylic acid.255～258 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e316.
Embodiment 37
With 4-propenyl-3-hydroxyl-9-oxygen-9H-xanthene (3.0 gram) ,-chlorine peroxybenzoic acid (8 gram) and the mixture of chloroform (500 milliliters) at room temperature stirred 5 hours, standing over night then.Salt of wormwood (20 gram) and water (400 milliliters) are joined in the mixture, with the resulting mixture of chloroform extraction.Dry chloroform layer, solvent evaporated.With acetone (500 milliliters) dissolving residuum, the mixture of chromium trioxide (5.5 gram) water (25 milliliters) and the vitriol oil (8.5 restrain) at room temperature is added dropwise in the solution that is stirring.After the standing over night, filtering mixt is extremely done filtrate vacuum-evaporation under vacuum.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.5 grams 1,2-dihydro-5-methyl-6-oxygen-6H-furo (2,3-b) xanthene-2-carboxylic acid.231～234 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e298.
Embodiment 38
With 4-propenyl-2-chloro-3-hydroxyl-1-methyl-9-oxygen-9H-xanthene (2.8 gram) ,-chlorine peroxybenzoic acid (6.4 gram) and the mixture of chloroform (300 milliliters) at room temperature stirred 5 hours, standing over night then.Add salt of wormwood (20 gram) and water (400 milliliters) in mixture, with the resulting mixture of chloroform extraction.Dry chloroform layer, solvent evaporated.With acetone (500 milliliters) dissolving residuum, at room temperature with chromium trioxide (5 gram), the mixture of the water (25 milliliters) and the vitriol oil (8 gram) is added dropwise in the solution that is stirring.After the standing over night, filtering mixt is extremely done mixture vacuum-evaporation.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.6 gram 4-chloro-1,2-dihydro-5-methyl-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acid.284～287 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e330.
Embodiment 39
With 4-propenyl-2-bromo-3-hydroxyl-9-oxygen-9H-xanthene (3.0 gram) ,-chlorine peroxybenzoic acid (10 gram), and the mixture of chloroform (250 milliliters) at room temperature stirred 5 hours, then standing over night.In mixture, add salt of wormwood (20 gram) and water (400 milliliters), with the resulting mixture of chloroform extraction.Dry chloroform layer, solvent evaporated.With acetone (300 milliliters) dissolving residuum, at room temperature the mixture with chromium trioxide (5 gram) water (25 milliliters) and the vitriol oil (8 gram) is added drop-wise in the solution that is stirring.After the standing over night, filtering mixt is extremely done filtrate vacuum-evaporation.After adding entry, the filtered and recycled solid crystal washes with water and drying.Use ethyl alcohol recrystallization, obtain 1.5 gram 4-chloro-1,2-two chloro-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acids.283～286 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e360.
Embodiment 40
With 4-propenyl-3-hydroxy-2-methyl-9-oxygen-9H-xanthene (12 gram) ,-chlorine peroxybenzoic acid (12 gram) and the mixture of chloroform (700 milliliters) at room temperature stirred 5 hours, standing over night then.20 gram salt of wormwood and 400 ml waters are joined in the mixture mixture that is generated to chloroform extraction.Dry chloroform layer, solvent evaporated.With acetone (2000 milliliters) dissolving residuum, at room temperature with chromium trioxide (34 gram), water (70 milliliters), and the mixture of the vitriol oil (30 milliliters) is added drop-wise in the solution that is stirring.After the standing over night, filtering mixt, vacuum is evaporated to filtrate dried.After adding entry, the filtered and recycled solid crystal washes with water and drying.With ethanol and N, the mixed solvent recrystallization of dinethylformamide obtains 1,2-dihydro-4-methyl-6-oxygen-6H-furo (2,3-c) xanthene-2-carboxylic acid.292～295 ℃ of fusing points.The mass spectrum of this compound has a part quasi-molecular ions at m/e296.
Claims (1)
1, the following logical formula I compound of preparation or when B is oh group the method for the non-toxic salt of above-claimed cpd, it is characterized in that,
(Y can be identical or different with Z, represents hydrogen atom for W wherein, X, halogen atom, or have the low-grade alkyl group of 1 to 4 carbon atom; A is hydrogen atom or generates the methene chain of ring texture with X or Y; B is a methylol groups, elementary alkoxycarbonyl group with 1 to 4 carbon atom, or carboxylic group are worked as X, Y and Z respectively are hydrogen atoms, when simultaneously A is the carboxylic group of hydrogen atom B or elementary alkoxycarbonyl group then W be not hydrogen atom and 7-position methyl group with following arbitrary consecutive steps preparation:
(a) compound of logical formula IV
(W wherein, X, Y and Z such as claim 1 definition) with general formula L-CH
2-B reaction (wherein L is a halogen atom, oh group, or as the acyloxy group of leavings group, B such as claim 1 definition), if B is an elementary alkoxycarbonyl group, hydrolysis reaction product at random then; Or (b) compound of general formula (V)
(W wherein, X and Y such as claim 1 definition) with cross acid-respons and generate general formula (III compound a);
(W wherein, X and Y such as claim 1 definition), at random this mixture and oxidant reaction are generated the compound of general formula (III b),
(W wherein, X and Y such as claim 1 definition), the carboxylic group of this compound of esterification arbitrarily.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59196796A JPS6176476A (en) | 1984-09-21 | 1984-09-21 | Xanthone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85107319A CN85107319A (en) | 1987-04-08 |
| CN1010777B true CN1010777B (en) | 1990-12-12 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN89102374A Expired CN1010777B (en) | 1984-09-21 | 1985-09-30 | The preparation method of xanthone derivative |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS6176476A (en) |
| KR (1) | KR860002492A (en) |
| CN (1) | CN1010777B (en) |
| ES (1) | ES8801298A3 (en) |
| SU (1) | SU1366059A3 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102643447B (en) * | 2007-08-21 | 2013-07-24 | 北京万和芯源生物技术有限公司 | Ultraviolet light assisted surface modification method and product with surface formed by means of method |
| CN102675672B (en) * | 2007-08-21 | 2014-06-18 | 北京万和芯源生物技术有限公司 | Ultraviolet aided surface modification method and product with surface formed by method |
| CN101372538B (en) * | 2007-08-21 | 2012-08-29 | 北京万和芯源生物技术有限公司 | Ultraviolet light assisted surface modification method and product with surface formed thereby |
| CN101270110B (en) * | 2008-04-29 | 2011-05-04 | 中国人民解放军第二军医大学 | Novel sulfonyl substituted benzophenone oxide compounds, prepraring method and application thereof |
| US8673920B2 (en) * | 2009-05-06 | 2014-03-18 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| CN102276564A (en) * | 2011-06-23 | 2011-12-14 | 徐州师范大学 | Synthetic method of 12-phenyl-benzo[b] xanthenetrione derivative |
| CN102617538A (en) * | 2012-03-08 | 2012-08-01 | 南京大学 | Xanthone type small molecule with effect of broad spectrum regulation on micro ribonucleic acid and synthesis method and application thereof |
| CN105294637B (en) * | 2015-08-08 | 2018-02-09 | 沈阳药科大学 | Nitrogenous * ketone derivatives and its preparation method and application |
| CN108047187B (en) * | 2017-11-22 | 2021-12-10 | 河南科技大学 | Preparation method of xanthone |
-
1984
- 1984-09-21 JP JP59196796A patent/JPS6176476A/en active Pending
-
1985
- 1985-09-20 KR KR1019850006900A patent/KR860002492A/en not_active Application Discontinuation
- 1985-09-20 SU SU853955801A patent/SU1366059A3/en active
- 1985-09-30 CN CN89102374A patent/CN1010777B/en not_active Expired
-
1987
- 1987-09-18 ES ES557745A patent/ES8801298A3/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ES557745A0 (en) | 1987-12-16 |
| CN85107319A (en) | 1987-04-08 |
| JPS6176476A (en) | 1986-04-18 |
| ES8801298A3 (en) | 1987-12-16 |
| SU1366059A3 (en) | 1988-01-07 |
| KR860002492A (en) | 1986-04-26 |
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