CN100999535A - 15-(14-deoxy 11,12 dehydro) andrographolide carbonic side derivate and preparation process thereof - Google Patents
15-(14-deoxy 11,12 dehydro) andrographolide carbonic side derivate and preparation process thereof Download PDFInfo
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Abstract
The present invention relates to carbon glycoside compound, and is especially 15-(14-deoxy-11, 12-dehydro)-andrographolide carbon glycoside derivative and its preparation process. The preparation process includes dewatering andrographolide as precursor compound, epoxidation and other reaction to obtain serial andrographolide derivatives; dissolving the derivatives and beta- carbon glycoside ketone in organic solvent and condensation reaction at certain temperature in the presence of catalyst for certain time. The derivative is significant in developing andrographolide.
Description
Technical field
The present invention relates to a kind of c-glycosides and its preparation method, relate in particular to a kind of rographolide carbon glycoside derivates and its preparation method.
Background technology
The carbon glycosides is the comparatively special class glycosides compound of structure, and its glycosyl is directly to be connected on the aglycon with the C-C key.Research to glycosides compound in the past few decades mainly is that S-and N-glycosides carry out around O-, and c-glycosides is because its complicacy analytically is less relatively to its research.In recent years along with the biological activity of c-glycosides gradually by cognition, the research of c-glycosides has been become the research focus of carbohydrate chemistry and biochemical field.
Rographolide (Andrographolide) is the diterpenes diterpenoids lactones compound that extracts in acanthaceous plant Herba Andrographis Andrographis paniculata (Bum.f.) Nees, be one of main component of Chinese medicine Herba Andrographis, have functions such as clearing heat and detoxicating, cool blood detumescence.Modern pharmacology studies show that, rographolide and derivative thereof have effects such as antiphlogistic antibacterial, anti-virus infection, antitumor, anti-cardiovascular disease, immunomodulatory, hepatic cholagogic and antifertility.The rographolide resource is extensive, and absorption is fast in animal body, drug effect is long, bioavailability is high, and does not have obvious toxic and side effects.In recent years, the research of rographolide is become the focus that receives much attention, but do not seen the report that C15-rographolide carbon glycoside derivates is arranged at present.Novel synthetic research, the Application Areas that will widen the carbon glycosides that contains the c-glycosides of rographolide skeleton promotes the well-being of mankind the carbon glycoside compound better.Simultaneously, this is to further development and use rographolide, and the Chinese materia medica modernization, the medicine of developing one's own intellectual property that promote China are also significant.
Summary of the invention
The object of the invention is to provide a series of novel rographolide carbon glycoside derivates: 15-(14-deoxidation-11,12-dehydrogenation)-rographolide carbon glycoside derivates; Another purpose is to provide its synthetic method, with the new drug of developing one's own intellectual property better.
For realizing the object of the invention, technical solution of the present invention is as follows:
15-(14-deoxidation-11,12-dehydrogenation)-rographolide carbon glycoside derivates has following general formula:
General formula 1 general formula 2
R in the general formula 1,2
1For (β-D-pyrans glycosyl-1-)-methyl; R
2Be methyl; R
3, R
4Be hydrogen or ring-type hydroxyl protecting group or COR ', wherein R ' is groups such as the saturated or unsaturated alkyl of C1-16, aromatic base, aromatic alkyl, alkenyl, heteroaryl, heteroaralkyl.The two hydroxyl protecting groups of described ring-type are CH
2, CMe
2, CH
3CH
2CH
2CH, PhMeC, PhCH, p-ClPhCH.
General formula 1 expression 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation andrographolidume derivative or 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation-3,19-acetal (ketone) andrographolidume derivative or 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation-3,19-acyloxy andrographolidume derivative; General formula 2 expression 15-(1-(β-D-pyrans glycosyl-1-) different third subunit) 14-deoxidation-11,12-dehydrogenation-8,17-epoxy andrographolidume derivative or 15-(1-(β-D pyrans glycosyl-1-) different third subunit)-14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3,19-acetal (ketone) andrographolidume derivative or 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation 8,17 epoxies-3,19-acyloxy andrographolidume derivative.
The method for preparing compound shown in the general formula 1: will (β-D-pyrans glycosyl-1-)-acetone and 14-deoxidation-11,12-dehydrogenation rographolide or 14-deoxidation-11,12-dehydrogenation-3,19-acetal (ketone) rographolide or 14-deoxidation-11,12-dehydrogenation-3, a kind of being dissolved in the organic solvent in the 19-acyloxy rographolide is under base catalysis, 10～80 ℃ were reacted 5～72 hours, and can obtain the rographolide carbon glycoside derivates shown in the general formula 1.
The method for preparing compound shown in the general formula 2: will (β-D-pyrrole south glycosyl-1-)-acetone and 14-deoxidation-11,12-dehydrogenation-8,17-epoxy rographolide or 14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3,19-acetal (ketone) rographolide or 14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3, a kind of being dissolved in the organic solvent in the 19-acyloxy rographolide, under base catalysis, 10～80 ℃ were reacted 5～72 hours, and can obtain the rographolide carbon glycoside derivates shown in the general formula 2.
Preparation general formula 1, the used organic solvent of general formula 2 rographolide carbon glycoside derivates is acetonitrile, ethanol, methyl alcohol, Virahol, 1, a kind of in 2-ethylene dichloride, methylene dichloride, chloroform, tetrachloro furans, the dioxane etc.; Used alkali is yellow soda ash, salt of wormwood, and saleratus, sodium bicarbonate, triethylamine, pyridine, N, a kind of in N-dimethyl aminopyridine and aliphatic amide and the aromatic amine etc., its consumption is 0.2～50% mole; The recrystallization solvent for use is a kind of in acetonitrile, ethanol, methyl alcohol, acetone, ethyl acetate, the tetrahydrofuran (THF); It is used that (β-D-pyrans glycosyl-1-)-acetone is (β-D-4-chloro-4-deoxidation-galactosyl-1-)-acetone, (β-D-glucosyl group-1-)-acetone, (β-D-galactosyl-1-)-acetone, (a kind of in β-D-xylosyl-1-)-β-glycosyls such as acetone-1-acetone, its molar ratio is for (β-D-pyrans glycosyl-1-)-acetone/lactone is 1/1.5～1/9.
The invention has the advantages that: 1,15-provided by the present invention (14-deoxidation-11; the 12-dehydrogenation)-rographolide carbon glycoside derivates preparation method is simple and convenient, mild condition, do not need protective group, deprotection directly to prepare; the yield height can be prepared rographolide carbon glycoside derivates easily.2, the present invention is grafted to c-glycosides on the rographolide, synthesize 15-(14-deoxidation-11, the 12-dehydrogenation)-rographolide carbon glycoside derivates, increased the wetting ability of rographolide compounds, can be used as pharmaceutical intermediate or lead compound and carry out further structural modification.3, the present invention is a lead compound with natural traditional Chinese medicine plant andrographolidume derivative, and it is abundant in china natural resources, and very strong region resources advantage is arranged, and provides a new way for further developing rographolide.
Embodiment
For can the present invention is described in detail better, it be as follows to give an actual example:
Embodiment 1: R shown in the preparation general formula 1
1=(β-D-4-chloro-4-deoxidation-galactosyl-1-)-methyl, R
2=methyl, R
3=R
4Derivative during=H
14-deoxidation-11,12-dehydrogenation rographolide 680mg, (β-D-4-chloro-4-deoxidation-galactosyl-1-)-acetone 238mg is dissolved in the 10ml methyl alcohol, adds 50mg yellow soda ash, 65 ℃ of reactions 6 hours.After reaction finishes, add chloroform 16ml dilution, add the silica gel suction filtration in the suction funnel and remove alkali in the system, concentration response system, column chromatography for separation get the 414mg faint yellow solid, are a pair of cis-trans isomerism mixture, and be suitable/anti-=1/1, yield 75%.Experimental data is as follows:
C
29H
41ClO
8.IR3391，2935，1744，1077，1031cm
-1；
1H?NMR(400MHz，DMSO，TMS)：δ8.01(s，1H)，7.80(s，1H，)，6.76(dd，2H，J＝10.4，15.6Hz)，6.16(dd，2H，J＝12.8，15.6?Hz)，5.37(w，2H，OH)，5.19(w，2H，OH)，5.07(w，2H，OH)，4.78(w，2H，OH)，4.78(s，2H)，4.44(s，2H)，4.34(d，2H，J＝2.8Hz)，4.03(m，2H)，3.85(d，2H，J＝10.8Hz)，3.63(d，4H，J＝5.6Hz)，3.42～3.17(overlap，13H)，2.86(d，1H，J＝13.6Hz)，2.69(d，1H，J＝13.6Hz)，2.37(m，4H)，1.99-1.98(overlap，9H)，1.10(s，6H)，0.77(s，6H)；
13C?NMR(100.6MHz，DMSO，TMS)：δ168.9，168.7，149.2，145.9，145.3，136.0，135.9，133.2，132.9，126.2，125.8，125.2，124.4，121.8，121.6，1084，79.2，79.1，78.8，77.3，73.2，73.0，70.8，70.1，64.7，62.9，60.9，60.0，53.9，42.6，39.5，39.3，39.1，38.7，38.2，36.5，27.9，23.4，23.3，17.5，17.2，15.7，14.3；HR-MS?m/z：[M+Na]
+?575.2382(calcd.575.2388).
Embodiment 2: R shown in the preparation general formula 2
1=(β-D-xylosyl-1-)-methyl, R
2=methyl, R
3=R
4Derivative during=H
14-deoxidation-11,12-dehydrogenation-8,17 epoxy rographolide 600mg, (β-D-xylosyl-1-)-acetone 190mg is dissolved in the 10ml ethanol, adds the 60mg sodium bicarbonate, 70 ℃ of reactions 6 hours.After reaction finishes, add chloroform 16ml dilution, add the silica gel suction filtration in the suction funnel and remove alkali in the system, concentration response system, column chromatography for separation get the 427mg faint yellow solid, are a pair of cis-trans isomerism mixture, and be suitable/anti-=1/1, yield 82%.Experimental data is as follows:
C
28H
40O
9.IR3410，2933，1748，1038em
-1；
1H?NMR(400MHz，DMSO，TMS)：δ7.92(s，0.5H)，7.80(s，0.5H)，6.30(m，1H)，6.08(m，1H)，5.02(w，4H，OH)，4.12(w，1H，OH)，3.81(d，1H，J＝10.9Hz)，3.63(m，1H)，3.38-3.17(6H，overlap)，3.16(m，1H)，3.06(m，1H)，2.90(m，1H)，2.65(m，2H)，2.45(m，1H)，2.18(m，1H)，1.91(s，3H)，1.06(s，3H)，0.88(s，3H)；
13C?NMR(100.6MHz，DMSO，TMS)：δ168.7，146.0，145.6，133.1，132.8，132.0，126.1，125.8，125.1，124.5，123.8，123.7，78.8，78.5，78.4，74.6，74.0，70.1，70.0，62.9，58.6，58.5，53.6，49.9，42.5，38.0，35.7，35.0，27.4，23.3，21.7，17.0，15.8；HR-MS?m/z：[M+Na]
+543.2658(calcd.543.2570).
Embodiment 3: and R1=shown in the preparation general formula 1 (β-D-galactosyl-1-)-methyl, R
2=methyl, R
3=R
4=CH
2The time derivative
14-deoxidation-11,12-dehydrogenation-3,19-formal rographolide 650mg, (β-D-galactosyl-1-)-acetone 220mg is dissolved in the 10ml acetonitrile, adds the 50mg triethylamine, 70 ℃ of reactions 6 hours.After reaction finished, concentration response system, column chromatography for separation got the 426mg faint yellow solid, are a pair of cis-trans isomerism mixture, and be suitable/anti-=1/1, yield 78%.Experimental data is as follows:
C
30H
42O
9.IR3400，2939，1753，1445，1026cm
-1；
1H?NMR(400MHz，CDCl
3，TMS)：δ7.41(s，1H)，7.32(s，1H)，6.90(m，1H)，6.14(d，1H，J＝15.6Hz)，4.90(s，2H)，4.78(s，2H)，4.29(s，2H)，4.26-3.42(14H，overlap)，2.01(s，3H)，1.41(s，3H)，0.92(s，3H)；
13C?NMR(100.6?MHz，CDCl
3，TMS)：δ169.7，148.8，147.3，147.1，132.6，132.3，127.9，127.7，122.9，110.3，88.5，87.3，83.1，81.0，80.6，79.9，72.4，69.9，64.8，62.5，55.0，39.5，38.5，38.0，37.1，26.6，25.9，22.6，21.7，18.5，18.1，16.8；HR-MS?m/z：[M+Na]
+569.2740(calcd.569.2727).
Embodiment 4: R shown in the preparation general formula 1
1=(β-D-glucosyl group-1-)-methyl, R
2=methyl, R
3=R
4Derivative during=H
14-deoxidation-11,12-dehydrogenation rographolide 640mg, (β-D-glucosyl group-1-)-acetone 220mg is dissolved in the 10ml tetrahydrofuran (THF), adds the 60mg pyridine, 60 ℃ of reactions 7 hours.After reaction finished, concentration response system, column chromatography for separation got the 385mg faint yellow solid, are a pair of cis-trans isomerism mixture, and be suitable/anti-=1/1, yield 72%.Experimental data is as follows:
C
29H
42O
9.IR3403，2935，1749，1081，1037cm
-1；
1H?NMR(400MHz，DMSO，TMS)：δ?8.00(s，1H)，7.85(s，1H)，6.76(m，1H)，6.16(dd，1H，J＝7.8，15.8Hz)，4.74(s，1H)，4.44(s，1H)，3.85(d，1H，J＝10.8Hz)，3.59(d，1H，J＝10.8Hz)，3.21(9H，overlap)，2.71(d，1H，13.6Hz)，1.90(s，3H)，1.10(s，6H)，0.77(s，6H)；
13C?NMR(100.6MHz，DMSO.TMS)：δ168.9，168.8，149.2，145.9，145.2，135.9，135.8，133.4，133.0，126.0，125.8，124.8，121.9，121.7，108.4，81.0，80.8，78.9，78.4，78.2，73.9，70.6，70.5，62.9，61.5，61.0，60.9，53.9，42.6，39.5，39.3，39.1，38.7，38.2，36.5，34.7，27.9，23.4，23.3，17.6，17.3，15.7；HR-MS?m/z：[M+Na]
+557.2727(calcd.557.2697).
Embodiment 5: R shown in the preparation general formula 2
1=(β-D-glucosyl group-1-)-methyl, R
2=methyl, R
3=R
4Derivative during=H
14-deoxidation-11,12-dehydrogenation-8,17-epoxy rographolide 500mg, (β-D-glucosyl group-1-)-acetone 220mg is dissolved in the 10ml ethanol, adds the 65mg saleratus, 75 ℃ of reactions 10 hours.After reaction finishes, add chloroform 16ml dilution, add the silica gel suction filtration in the suction funnel and remove alkali in the system, concentration response system, column chromatography for separation get the 429mg faint yellow solid, are a pair of cis-trans isomerism mixture, and be suitable/anti-=1/1, yield 78%.Experimental data is as follows:
C
29H
42O
10.IR3409，2933，1747，1038cm
-1；
1H?NMR(400MHz，DMSO，TMS)：δ7.95(s，1H)，7.81(s，1H)，630(dd，1H，J＝9.9Hz，15.6Hz)，6.12(dd，1H，J＝6.7，15.6Hz)，3.99(dd，1H，J＝7.0Hz)，3.81(d，1H，J＝12.4Hz)，3.56-3.17(10H，overlap)，2.99(m，1H)，2.87(m，2H)，2.65(m，1H)，2.48(d，1H，J＝4.5Hz)，2.18(dd，1H，J＝4.1Hz，9.7Hz)，1.95(s，3H)，1.06(s，3H)，0.88(s，3H)；
13C?NMR(100.6?MHz，DMSO，TMS)：δ169.1，169.0，146.2，145.4，133.5，133.1，132.1，132.0，126.1，126.0，125.9，125.1，124.1，123.9，81.2，81.0，78.9，78.5，74.8，74.1，63.1，61.7，60.2，58.8，53.8，50.1，45.9，42.7，38.2，35.9，34.9，27.6，23.5，21.9，21.2，17.8，17.5，16.0，14.5；HR-MS?m/z：[M+Na]
+573.2662(calcd.573.2676).
Above embodiment is raw materials used to be made by the following method:
14-deoxidation-11, the preparation of 12-dehydrogenation rographolide: the admixture solvent that rographolide is placed toluene and pyridine, aluminium sesquioxide is a catalyzer, backflow 6-10 hour to reacting completely, pumping rate, solvent evaporated gets white crystals with re-crystallizing in ethyl acetate and promptly makes 14-deoxidation-11,12-dehydrogenation rographolide.
14-deoxidation-11,12-dehydrogenation-8, the preparation of 17-epoxy rographolide: with 14-deoxidation-11,12 dehydrogenation rographolide and m-CPBA is to feed intake at 1: 1.2 in molar ratio, and solvent is a chloroform, stirring at room 1.5-5 hour, uses saturated NaHCO then respectively
3, the NaCl aqueous solution and H
2The O washing, the organic layer concentrating under reduced pressure, getting white crystals with re-crystallizing in ethyl acetate is 14-deoxidation-11,12-dehydrogenation-8,17-epoxy rographolide.
14-deoxidation-11,12-dehydrogenation-3, the preparation of 19-acetal (ketone) rographolide: in flask at the bottom of the 25mL garden, add 14-deoxidation-11,12-dehydrogenation rographolide (0.5mmol), sulfuric acid (98%) solution of aldehyde or ketone (0.6mmol) and THF, sulfuric acid (98%) concentration is controlled at the 0.5-0.6% volumetric concentration, stirred backflow 1.5-2.5 hour down, solvent evaporated adds the chloroform dissolving, uses saturated NaHCO then respectively
3, the NaCl aqueous solution and H
2The O washing, the organic layer concentrating under reduced pressure, getting white crystals with re-crystallizing in ethyl acetate is 14-deoxidation-11,12-dehydrogenation-3,19-acetal (ketone) rographolide.
(the mutter preparation of glycosyl-1-)-acetone of β-D-ratio makes according to following following document:
[1]Rodrigues，F，；Canac?Y.；Lubineau，A.Chem?commun.2000，20，2049-2050.
[2]Liu，F.-W.；Liu，H.-M.；Ke，Y.；Zhang，J.-Y.Carbohydr.Res.2004，339，2651-2656.
[3]Liu，F.-W.；Zhang，Y.-B.；Liu，H.-M.；Song，X.-P?Carbohy?dr.Res.2005，340，489-495.
Claims (10)
1,15-(14-deoxidation-11, the 12-dehydrogenation)-rographolide carbon glycoside derivates, it is characterized in that, has general formula 1 structure, general formula 1 expression 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation andrographolidume derivative or 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation-3,19-aldehydes or ketones andrographolidume derivative or the 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11 that contracts, 12-dehydrogenation-3,19-acyloxy andrographolidume derivative:
General formula 1
R
1For (β-D-pyrans glycosyl-1-)-methyl; R
2Be methyl; R
3, R
4Be hydrogen, ring-type hydroxyl protecting group or COR ', wherein R ' is saturated or unsaturated alkyl, aromatic base, aromatic alkyl, alkenyl, heteroaryl or a heteroaralkyl of C1-16.
2, according to the described 15-of claim 1 (14-deoxidation-11,12-dehydrogenation)-rographolide carbon glycoside derivates, it is characterized in that the ring-type hydroxyl protecting group is CH
2Or CMe
2Or CH
3CH
2CH
2CH or PhMeC or PhCH or p-ClPhCH.
3,15-(14-deoxidation-11, the 12-dehydrogenation)-the rographolide carbon glycosides dirt thing that spreads out, it is characterized in that, have general formula 2 structures, general formula 2 expression 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation-8,17-epoxy andrographolidume derivative or 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3,19-contract aldehydes or ketones andrographolidume derivative or 15-(1-(β-D-pyrans glycosyl-1-)-different third subunit)-14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3, the 19-acyloxy rographolide dirt thing that spreads out:
General formula 2
R
1For (β-D-pyrans glycosyl-1-)-methyl; R
2Be methyl; R
3, R
4Be hydrogen, ring-type hydroxyl protecting group or COR '; Wherein R ' is saturated or unsaturated alkyl, aromatic base, aromatic alkyl, alkenyl, heteroaryl or a heteroaralkyl of C1-16.
4, according to the described 15-of claim 3 (14-deoxidation-11,12-dehydrogenation)-rographolide carbon glycoside derivates, it is characterized in that the ring-type hydroxyl protecting group is CH
2Or CMe
2Or CH
3CH
2CH
2CH or PhMeC or PhCH or p-ClPhCH.
5, according to the described 15-of claim 1 (14-deoxidation-11, the 12-dehydrogenation)-preparation method of rographolide carbon glycoside derivates, it is characterized in that, will (β-D-pyrans glycosyl-1-)-acetone and 14-deoxidation-11,12-dehydrogenation rographolide or 14-deoxidation-11,12-dehydrogenation-3,19-contract aldehydes or ketones rographolide or 14-deoxidation-11,12-dehydrogenation-3, a kind of being dissolved in the organic solvent in the 19-acyloxy rographolide, under base catalysis, 10～80 ℃ of reactions, 5～72 hours, can obtain the carbon glycoside derivates shown in the general formula 1; Used organic solvent is acetonitrile, ethanol, methyl alcohol, Virahol, 1 in the reaction, a kind of in 2-ethylene dichloride, methylene dichloride, chloroform, tetrahydrofuran (THF), the dioxane.
6,15-as claimed in claim 5 (14-deoxidation-11, the 12-dehydrogenation)-rographolide carbon glycoside derivates preparation method, it is characterized in that, it is used that (β-D-pyrans glycosyl-1-)-acetone is that (β-D-4-chloro-4-deoxidation-galactosyl-1-)-acetone, (β-D-glucosyl group-1-)-acetone, (β-D-galactosyl-1-)-acetone, (a kind of in β-D-xylosyl-1-)-acetone, its molar ratio is for (β-D-pyrans glycosyl-1-)-acetone/lactone is 1/1.5～1/9.
7,15-as claimed in claim 5 (14-deoxidation-11, the 12-dehydrogenation)-and the preparation method of rographolide carbon glycoside derivates, it is characterized in that catalyst system therefor is a yellow soda ash in the reaction, salt of wormwood, saleratus, sodium bicarbonate, triethylamine, pyridine, N, N-dimethyl aminopyridine, and a kind of in aliphatic amide and the aromatic amine; Consumption is 0.2～50% mole.
8, according to the described 15-of claim 3 (14-deoxidation-11, the 12-dehydrogenation)-preparation method of rographolide carbon glycoside derivates, it is characterized in that, will (β-D-pyrrole food in one's mouth glycosyl-1-)-acetone and 14-deoxidation-11,12-dehydrogenation-8,17-epoxy rographolide or 14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3,19-contract aldehydes or ketones rographolide or 14-deoxidation-11,12-dehydrogenation-8,17-epoxy-3, a kind of being dissolved in the organic solvent in the 19-acyloxy rographolide, 10～80 ℃ were reacted 5～72 hours under base catalysis, can obtain the carbon glycoside derivates shown in the general formula 2; Used organic solvent is acetonitrile, ethanol, methyl alcohol, Virahol, 1 in the reaction, a kind of in 2-ethylene dichloride, methylene dichloride, chloroform, tetrahydrofuran (THF), the dioxane.
9,15-as claimed in claim 8 (14-deoxidation-11, the 12-dehydrogenation)-rographolide carbon glycoside derivates preparation method, it is characterized in that, it is used that (β-D-pyrans glycosyl-1-)-acetone is that (β-D-4-chloro-4-deoxidation-galactosyl-1-)-acetone, (β-D-glucosyl group-1-)-acetone, (β-D-galactosyl-1-)-acetone, (a kind of in β-D-xylosyl-1-)-acetone, its molar ratio is for (β-D-pyrans glycosyl-1-)-acetone/lactone is 1/1.5～1/9.
10,15-as claimed in claim 8 (14-deoxidation-11, the 12-dehydrogenation)-and the spread out preparation method of dirt thing of rographolide carbon glycosides, it is characterized in that catalyst system therefor is a yellow soda ash in the reaction, salt of wormwood, saleratus, sodium bicarbonate, triethylamine, pyridine, N, N-dimethyl aminopyridine, and a kind of in aliphatic amide and the aromatic amine; Consumption is 0.2～50% mole.
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| CN100528894C CN100528894C (en) | 2009-08-19 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101972247A (en) * | 2010-10-22 | 2011-02-16 | 郑州大学 | Medicinal application of 15-benzyl subunit-1 4-deoxy-11,12-dehydrogenation andrographolide derivative |
| CN103145659A (en) * | 2012-04-12 | 2013-06-12 | 江西青峰药业有限公司 | Composition of sodium (or potassium) 17-hydro-9-dehydroandrographolide-3-sulphate, sodium (or potassium) 17-hydro-9-dehydroandrographolide-19-sulphate and sodium (or potassium) 17-hydro-9-dehydroandrographolide-3,19-disulfate, and use of the composition in drug preparation |
| CN113264910A (en) * | 2021-05-21 | 2021-08-17 | 石家庄四药有限公司 | Recrystallization method of andrographolide C15 substituted derivative |
-
2007
- 2007-01-05 CN CNB2007100538067A patent/CN100528894C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101972247A (en) * | 2010-10-22 | 2011-02-16 | 郑州大学 | Medicinal application of 15-benzyl subunit-1 4-deoxy-11,12-dehydrogenation andrographolide derivative |
| CN101972247B (en) * | 2010-10-22 | 2012-06-06 | 郑州大学 | Medicinal application of 15-benzyl subunit-1 4-deoxy-11,12-dehydrogenation andrographolide derivative |
| CN103145659A (en) * | 2012-04-12 | 2013-06-12 | 江西青峰药业有限公司 | Composition of sodium (or potassium) 17-hydro-9-dehydroandrographolide-3-sulphate, sodium (or potassium) 17-hydro-9-dehydroandrographolide-19-sulphate and sodium (or potassium) 17-hydro-9-dehydroandrographolide-3,19-disulfate, and use of the composition in drug preparation |
| CN113264910A (en) * | 2021-05-21 | 2021-08-17 | 石家庄四药有限公司 | Recrystallization method of andrographolide C15 substituted derivative |
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| Publication number | Publication date |
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| CN100528894C (en) | 2009-08-19 |
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