CN102659888A - Cucurbitacin derivatives and preparation method thereof - Google Patents
Cucurbitacin derivatives and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a plurality of new derivatives of cucurbitacin B and cucurbitacin E, salts of the cucurbitacin B and the cucurbitacin E, and a preparation method of the new derivatives. The new derivatives and salts of the cucurbitacin B and the cucurbitacin E have common basic structure and substantially same properties with cucurbitacin B and cucurbitacin E; have good anti-cancer, anti-virus, anti-inflammatory and liver-protecting effects, and low toxic and side effects.
Description
Technical field
The present invention relates to the multiple verivate of cucurbitacin, be specifically related to the multiple verivate of Cucurbitacin B and E, also relate to the preparation method of these verivates.
Background technology
Cucurbitacin (cucurbitacin) belongs to the 19-methyl and appears at one type of tetracyclic triterpenoids compound on the C-9 position; Mainly be distributed in the cucurbitaceous plant, in higher plants such as Cruciferae, scrophulariaceae, Begoniaceae, Elaeocarpaceae, Datiscaceceae and some macro fungis, discovery arranged also.The extract of cucurbit prime system cucurbitaceous plant muskmelon (Cucumis melo L.) muskmelon pedicel, cucurbitacin has multiple biological activity, has the detoxifcation heat-clearing, and the effect of dampness removing removing jaundice is the effective Chinese patent medicine that is used to treat chronic hepatitis and primary hepatocarcinoma clinically.
Ancient Times in China just adopts Chinese medicine muskmelon (Cucumis melo L.) muskmelon pedicel to control jaundice, again can be emetic, eliminate the phlegm, be used for sputum place food.Begin the establishment along with the cucurbitacin chemical structure sixties, abroad the someone studies its antitumor action.Isolate compositions such as Cucurbitacin B, E the domestic beginning of the seventies from the Chinese medicine Muskmelon Base, and carried out pharmacological researches such as antitumor, immunostimulant and anti-hepatitis.The pharmacological action of report has: cell toxicant and antitumous effect; Anti-chemical carcinogenesis; Protect the liver, antihepatitic activity; Improve immunologic function; To cardiovascular effect; Anti-inflammatory; Suppress the effect of hepatic fibroplasia; Can also move by stimulating gastrointestinal in addition, can also practise contraception.
In our research, found that some novel derivatives of Cucurbitacin B and E, these novel derivatives have and Cucurbitacin B, the basic the same effect of E through the method for chemosynthesis, the present invention has been born.
Summary of the invention
First purpose of the present invention provides the multiple novel derivative of Cucurbitacin B and E and their salt; Second purpose of the present invention provides the preparation method of the novel derivative of Cucurbitacin B and E.
The invention provides the novel derivative of the novel derivative of six kinds of Cucurbitacin Bs, six kinds of Cucurbitacin Es and their pharmacy acceptable salt,
The chemical structure of these novel derivatives is following:
The Cucurbitacin B verivate of formula I, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ7.01(d,J=12Hz,1H),6.29(d,J=12Hz,1H),5.51(t,J=8.4Hz,1H),4.08(m,1H),3.23(m,1H),2.29-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,6H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.31(s,6H),1.30(s,3H),1.14(t,J=8.4,3H),1.04(s,6H).MS?573[M+H]
+。
The Cucurbitacin B verivate of formula II, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ7.01(d,J=12Hz,1H),6.29(d,J=12Hz,1H),5.51(t,J=8.4Hz,1H),4.08(m,1H),3.23(m,1H),2.29-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,8H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.31(s,6H),1.30(s,3H),1.04(s,6H),0.9(t,J=8.4,3H).MS?587[M+H]
+。
The Cucurbitacin B verivate of formula III, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ5.51(t,J=8.4Hz,1H),4.08(m,1H),3.23(m,1H),2.29-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,12H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.31(s,6H),1.30(s,3H),1.14(t,J=8.4,3H),1.04(s,6H).MS?575[M+H]
+。
The Cucurbitacin B verivate of formula IV, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ5.51(t,J=8.4Hz,1H),4.08(m,1H),3.23(m,1H),2.29-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,12H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.31(s,6H),1.30(s,3H),1.04(s,6H),0.9(t,J=8.4,3H).MS?587[M+H]
+。
The Cucurbitacin B verivate of formula V, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ7.01(d,J=12Hz,1H),6.29(d,J=12Hz,1H),5.51(t,J=8.4Hz,1H),5.03(m,1H),4.08(m,1H),3.79-3.49(m,5H),3.40(m,1H),2.85(m,1H),2.27-2.02(m,8H),1.85-1.69(m,4H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.31(s,6H),1.30(s,3H),1.04(s,6H).MS?721[M+H]
+。
The Cucurbitacin B verivate of formula VI, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ5.51(t,J=8.4Hz,1H),5.03(m,1H),4.08(m,1H),3.79-3.49(m,5H),3.40(m,1H),2.85(m,1H),2.27-2.02(m,12H),1.85-1.69(m,4H),1.60-1.46(m,2H),1.47(s,?6H),1.38(s,3H),1.31(s,6H),1.30(s,3H),1.04(s,6H).MS?723[M+H]
+。
The Cucurbitacin E verivate of formula X, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ7.01(d,J=12Hz,1H),6.66(s,1H),6.29(d,J=12Hz,1H),5.51(t,J=8.4Hz,1H),3.23(m,1H),2.85(m,1H),2.29-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,4H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.36(s,6H),1.30(s,3H),1.14(t,J=8.4,3H),1.04(s,6H).MS?571[M+H]
+。
The Cucurbitacin E verivate of formula XI, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ7.01(d,J=12Hz,1H),6.66(s,1H),6.29(d,J=12Hz,1H),5.51(t,J=8.4Hz,1H),3.23(m,1H),2.85(m,1H),2.32-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,6H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.36(s,6H),1.30(s,3H),1.04(s,6H),0.90(t,J=8.4,3H).MS?585[M+H]
+。
The Cucurbitacin E verivate of formula XII, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ6.66(s,1H),5.51(t,J=8.4Hz,1H),3.23(m,1H),2.85(m,1H),2.29-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,8H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.36(s,6H),1.30(s,3H),1.14(t,J=8.4,3H),1.04(s,6H).MS?573[M+H]
+。
The Cucurbitacin E verivate of formula XIII, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ6.66(s,1H),5.51(t,J=8.4Hz,1H),3.23(m,1H),2.85(m,1H),2.32-2.27(m,3H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,10H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.36(s,6H),1.30(s,3H),1.04(s,6H),0.90(t,J=8.4,3H).MS?585[M+H]
+。
The Cucurbitacin E verivate of formula XIV, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ7.01(d,J=12Hz,1H),6.66(s,1H),6.29(d,J=12Hz,1H),5.51(t,J=8.4Hz,1H),5.03(m,1H),3.79-3.49(m,5H),3.40(m,1H),3.23(m,1H),2.85(m,1H),2.29-2.27(m,6H),2.16(m,1H),2.04-2.02(m,2H),1.86-1.71(m,4H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.36(s,6H),1.30(s,3H),1.04(s,6H).MS?719[M+H]
+。
The Cucurbitacin E verivate of formula XV, illustrate its structure and mass spectrum calculating compound molecular weight through nuclear magnetic resonance technique:
1H-NMR(400MHz,CDCl3)δ6.66(s,1H),5.51(t,J=8.4Hz,1H),5.03(m,1H),3.79-3.49(m,5H),3.40(m,1H),3.23(m,1H),2.85(m,1H),2.29-2.27(m,10H),2.16(m,1H),2.04-2.02(m,2H),1.86-?1.71(m,4H),1.60-1.46(m,2H),1.47(s,6H),1.38(s,3H),1.36(s,6H),1.30(s,3H),1.04(s,6H).MS721[M+H]
+。
The synthetic route of the Cucurbitacin E verivate of the Cucurbitacin B verivate of formula I (B-1), formula II (B-2), formula III (B-3), formula IV (B-4) and formula X (E-1), formula XI (E-2), formula XI (E-3), formula XIII (E-4) is following:
The synthetic route of the Cucurbitacin E verivate of the Cucurbitacin B verivate of formula V (B-5), formula VI (B-6) and formula XIV (E-5), formula XV (E-6) is following:
Newfound above-mentioned six kinds of Cucurbitacin B verivates and six kinds of Cucurbitacin E verivates and their salt; Owing to have common substruction with Cucurbitacin B, E respectively; So character is also basically the same with Cucurbitacin B, E; Have good anticancer, antiviral, anti-inflammatory and protect the liver dirty effect, and toxic side effect is lower.
Embodiment
Come further to set forth the present invention in conjunction with above-mentioned synthetic route.
(1) B-1-1's is synthetic: existing Cucurbitacin B (559 milligrams, 1.0 mmoles) is dissolved in 10 ml methanol, adds the lithium hydroxide aqueous solution (1 milliliter) of 1N then; Stirring at room 2 hours concentrates, and resistates dissolves with methylene dichloride; With soda lye wash; Organic layer is dry to be concentrated, and gets 502 milligrams of white solids, yield 97.2%.
(2) B-1's is synthetic: will synthesize good B-1-1 (51.6 milligrams, 0.1 mmole) and be dissolved in 10 milliliters of methylene dichloride, and add pyridine (10 milligrams) then; Add propionyl chloride (10 milligrams) again, room temperature reaction 2 hours, reaction finishes; Reaction solution is with acid rinsing; Organic layer is dry to be concentrated, and the resistates column chromatography purification obtains 42 milligrams of white solids, yield 74%.
(3) E-1-1's is synthetic: existing Cucurbitacin E (557 milligrams, 1.0 mmoles) is dissolved in 10 ml methanol, adds the lithium hydroxide aqueous solution (1 milliliter) of 1N then; Stirring at room 2 hours concentrates, and resistates dissolves with methylene dichloride; With soda lye wash; Organic layer is dry to be concentrated, and gets 498 milligrams of white solids, yield 96.8%.
(4) E-1's is synthetic: will synthesize good E-1-1 (51.4 milligrams, 0.1 mmole) and be dissolved in 10 milliliters of methylene dichloride, and add pyridine (10 milligrams) then; Add propionyl chloride (10 milligrams) again, room temperature reaction 2 hours, reaction finishes; Reaction solution is with acid rinsing; Organic layer is dry to be concentrated, and the resistates column chromatography purification obtains 47 milligrams of white solids, yield 83%.
(5) B-2's is synthetic: will synthesize good B-1-1 (51.6 milligrams, 0.1 mmole) and be dissolved in 10 milliliters of methylene dichloride, and add pyridine (10 milligrams) then; Add butyryl chloride (10 milligrams) again, room temperature reaction 2 hours, reaction finishes; Reaction solution is with acid rinsing; Organic layer is dry to be concentrated, and the resistates column chromatography purification obtains 45 milligrams of white solids, yield 77%.
(6) E-2's is synthetic: will synthesize good E-1-1 (51.4 milligrams, 0.1 mmole) and be dissolved in 10 milliliters of methylene dichloride, and add pyridine (10 milligrams) then; Add butyryl chloride (11 milligrams) again, room temperature reaction 2 hours, reaction finishes; Reaction solution is with acid rinsing; Organic layer is dry to be concentrated, and the resistates column chromatography purification obtains 50 milligrams of white solids, yield 86%.
(7) B-3's is synthetic: compd B-1 (57.2 milligrams) is dissolved in 10 milliliters of ethanol, adds the palladium carbon of 0.3 gram 10% then, nitrogen replacement, hydrogen exchange then; Keep 2atm pressure, stirring reaction 1 hour filters; Concentrate, get 56.9 milligrams of white solids, yield 99%.
(8) B-4's is synthetic: compd B-2 (58.4 milligrams) is dissolved in 10 milliliters of ethanol, adds the palladium carbon of 0.3 gram 10% then, nitrogen replacement, hydrogen exchange then; Keep 2atm pressure, stirring reaction 1 hour filters; Concentrate, get 55.2 milligrams of white solids, yield 94%.
(9) E-3's is synthetic: compd E-1 (57 milligrams) is dissolved in 10 milliliters of ethanol, adds the palladium carbon of 0.3 gram 10% then, nitrogen replacement, hydrogen exchange then; Keep 2atm pressure, stirring reaction 1 hour filters; Concentrate, get 56.1 milligrams of white solids, yield 98.4%.
(10) E-4's is synthetic: compd E-2 (58.2 milligrams) is dissolved in 10 milliliters of ethanol, adds the palladium carbon of 0.3 gram 10% then, nitrogen replacement, hydrogen exchange then; Keep 2atm pressure, stirring reaction 1 hour filters; Concentrate, get 56.5 milligrams of white solids, yield 97%.
(11) G-1's is synthetic: glucose (1.8 grams, 10 mmoles) is dissolved in 20 milliliters of acetone, adds 1 then; 1-Propanal dimethyl acetal (2.1 grams, 20 mmoles) and sulfuric acid (1), stirring at room 1 hour; Be concentrated into to the greatest extent, resistates is with acetic acid ethyl dissolution, with water washing; Organic layer is dry to be concentrated, and obtains 2.13 gram colorless oil, yield 82%.
(12) B-5-1's is synthetic: with (81.5 milligrams in existing Cucurbitacin B (559 milligrams, 1 mmole), synthetic good G-1 (260 milligrams, 1 mmole), zinc oxide; 1 mmole) be dissolved in 10 ml methanol, stirring at room one hour is concentrated into to the greatest extent; Resistates is with acetic acid ethyl dissolution, and with the saturated brine washing, organic layer is dry to be concentrated; Residuum obtains 624 milligrams of white solids, yield 78% with column chromatography purification.
(13) B-5's is synthetic: will synthesize good B-5-1 (400 milligrams, 0.5 mmole) and be dissolved in 10 milliliters of toluene, and add (86 milligrams of tosic acid then; 0.5 mmole), stirring at room 18 hours, reaction finishes; In reaction solution, add the saturated sodium bicarbonate aqueous solution washing, organic layer is dry to be concentrated, and resistates is with column chromatography purification; Obtain 248 milligrams of white solids, yield 69%.
(14) E-5-1's is synthetic: with (81.5 milligrams in existing Cucurbitacin E (556 milligrams, 1 mmole), synthetic good G-1 (260 milligrams, 1 mmole), zinc oxide; 1 mmole) be dissolved in 10 ml methanol, stirring at room one hour is concentrated into to the greatest extent; Resistates is with acetic acid ethyl dissolution, and with the saturated brine washing, organic layer is dry to be concentrated; Residuum obtains 606 milligrams of white solids, yield 76% with column chromatography purification.
(15) E-5's is synthetic: will synthesize good E-5-1 (400 milligrams, 0.5 mmole) and be dissolved in 10 milliliters of toluene, and add (86 milligrams of tosic acid then; 0.5 mmole), stirring at room 18 hours, reaction finishes; In reaction solution, add the saturated sodium bicarbonate aqueous solution washing, organic layer is dry to be concentrated, and resistates is with column chromatography purification; Obtain 240 milligrams of white solids, yield 67%.
(16) B-6's is synthetic: compd B-5 (72 milligrams) is dissolved in 10 milliliters of ethanol, adds the palladium carbon of 0.3 gram 10% then, nitrogen replacement, hydrogen exchange then; Keep 2atm pressure, stirring reaction 1 hour filters; Concentrate, get 68.6 milligrams of white solids, yield 95%.
(17) E-6's is synthetic: compd E-5 (72 milligrams) is dissolved in 10 milliliters of ethanol, adds the palladium carbon of 0.3 gram 10% then, nitrogen replacement, hydrogen exchange then; Keep 2atm pressure, stirring reaction 1 hour filters; Concentrate, get 69.8 milligrams of white solids, yield 97%.
The Cucurbitacin B novel derivative B-1 that makes, B-2, B-3, B-4, B-5, B-6 and Cucurbitacin E novel derivative E-1, E-2, E-3, E-4, E-5, E-6; Function is identical with existing Cucurbitacin B, E respectively, the effect that anticancer, antiviral, anti-inflammatory is arranged and protect the liver.In other words, the method for pharmacology of studying these Cucurbitacin Bs and E novel derivative is with existing Cucurbitacin B, E, so do not give unnecessary details at this, the pharmacological action report of relevant existing Cucurbitacin B, E is specifically referring to following disclosed document:
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Claims (10)
1. the Cucurbitacin B verivate represented of formula I, formula II, formula III, formula IV, formula V or formula VI, perhaps its pharmacy acceptable salt:
(V)
2. prepare the method for the Cucurbitacin B verivate of formula I or formula II, it is characterized in that:
At first, Cucurbitacin B is dissolved in the methyl alcohol, adds lithium hydroxide aqueous solution then, stirring at room concentrates, and resistates dissolves with methylene dichloride, and with soda lye wash, organic layer is dry to be concentrated, and gets the white solid that formula VII representes,
Then, the compound dissolution among the formula VII in methylene dichloride, is added pyridine then, add propionyl chloride again; Room temperature reaction, reaction finishes, and reaction solution is with acid rinsing; Organic layer is dry to be concentrated, and the resistates column chromatography purification obtains white solid, is the Cucurbitacin B verivate of said formula I;
Perhaps, the compound dissolution among the formula VII in methylene dichloride, is added pyridine then, add butyryl chloride again; Room temperature reaction, reaction finishes, and reaction solution is with acid rinsing; Organic layer is dry to be concentrated, and the resistates column chromatography purification obtains white solid, is the Cucurbitacin B verivate of said formula II.
3. prepare the method for the Cucurbitacin B verivate of formula III or formula IV, it is characterized in that:
The Cucurbitacin B verivate of formula I is dissolved in the ethanol, adds palladium carbon then, nitrogen replacement, hydrogen exchange keeps 2 atm pressure then, and stirring reaction filters, and concentrates, and gets white solid, is the Cucurbitacin B verivate of said formula III;
Perhaps, the Cucurbitacin B verivate of formula II is dissolved in the ethanol, adds palladium carbon then, nitrogen replacement, hydrogen exchange keeps 2 atm pressure then, stirring reaction filters, concentrate, white solid, be the Cucurbitacin B verivate of said formula IV.
4. prepare the method for the Cucurbitacin B verivate of formula V, it is characterized in that:
(1) glucose is dissolved in the acetone, adds 1 then, 1-Propanal dimethyl acetal and sulfuric acid, stirring at room is concentrated into to the greatest extent, and resistates is with acetic acid ethyl dissolution, and with water washing, organic layer is dry to be concentrated, the colorless oil that the formula VIII of obtaining representes,
(2) compound among Cucurbitacin B, the formula VIII, zinc oxide are dissolved in the methyl alcohol, stirring at room is concentrated into to the greatest extent; Resistates is with acetic acid ethyl dissolution, and with the saturated brine washing, organic layer is dry to be concentrated; Residuum is with column chromatography purification, the white solid that the formula IX of obtaining representes
(3) with the compound dissolution among the formula IX in toluene, add tosic acid then, stirring at room; Reaction finishes; In reaction solution, add the saturated sodium bicarbonate aqueous solution washing, organic layer is dry to be concentrated, and resistates is with column chromatography purification; Obtain white solid, be the Cucurbitacin B verivate of said formula V.
5. prepare the method for the Cucurbitacin B verivate of formula VI, it is characterized in that:
The Cucurbitacin B verivate of formula V is dissolved in the ethanol, adds palladium carbon then, nitrogen replacement, hydrogen exchange keeps 2 atm pressure then, and stirring reaction filters, and concentrates, and gets white solid, is the Cucurbitacin B verivate of said formula VI.
6. the Cucurbitacin E verivate represented of formula X, formula XI, formula XII, formula XIII, formula XIV or formula XV, perhaps its pharmacy acceptable salt:
7. prepare the method for the Cucurbitacin E verivate of formula X or formula XI, it is characterized in that:
At first, Cucurbitacin E is dissolved in the methyl alcohol, adds lithium hydroxide aqueous solution then, stirring at room concentrates, and resistates dissolves with methylene dichloride, and with soda lye wash, organic layer is dry to be concentrated, and gets the white solid that formula XVI representes,
(XVI)；
Then, the compound dissolution among the formula XVI in methylene dichloride, is added pyridine then, add propionyl chloride again, room temperature reaction, reaction finishes, and reaction solution is with acid rinsing, and organic layer is dry to be concentrated, and the resistates column chromatography purification obtains the Cucurbitacin E verivate of said formula X;
Perhaps, the compound dissolution among the formula XVI in methylene dichloride, is added pyridine then; Add butyryl chloride again, room temperature reaction, reaction finishes; Reaction solution is with acid rinsing, and organic layer is dry to be concentrated, and the resistates column chromatography purification obtains the Cucurbitacin E verivate of said formula XI.
8. prepare the method for the Cucurbitacin E verivate of formula XII or formula XIII, it is characterized in that:
The Cucurbitacin E verivate of formula X is dissolved in the ethanol, adds palladium carbon then, nitrogen replacement, hydrogen exchange keeps 2 atm pressure then, and stirring reaction filters, and concentrates, and gets the Cucurbitacin E verivate of said formula XII;
Perhaps, the Cucurbitacin E verivate of formula XI is dissolved in the ethanol, adds palladium carbon then, nitrogen replacement, hydrogen exchange keeps 2 atm pressure then, stirring reaction filters, concentrate, the Cucurbitacin E verivate of said formula XIII.
9. prepare the method for the Cucurbitacin E verivate of formula XIV, it is characterized in that:
(1) glucose is dissolved in the acetone, adds 1 then, 1-Propanal dimethyl acetal and sulfuric acid, stirring at room is concentrated into to the greatest extent, and resistates is with acetic acid ethyl dissolution, and with water washing, organic layer is dry to be concentrated, and obtains the colorless oil that said formula VIII representes,
（VIII）；
(2) compound among Cucurbitacin E, the formula VIII, zinc oxide are dissolved in the methyl alcohol, stirring at room is concentrated into to the greatest extent; Resistates is with acetic acid ethyl dissolution, and with the saturated brine washing, organic layer is dry to be concentrated; Residuum is with column chromatography purification, the white solid that the formula XVII of obtaining representes
(3) with the compound dissolution among the formula XVII in toluene, add tosic acid then, stirring at room; Reaction finishes, and in reaction solution, adds the saturated sodium bicarbonate aqueous solution washing, and organic layer is dry to be concentrated; Resistates obtains the Cucurbitacin E verivate of said formula XIV with column chromatography purification.
10. prepare the method for the Cucurbitacin E verivate of formula XV, it is characterized in that:
The Cucurbitacin E verivate of formula XIV is dissolved in the ethanol, adds palladium carbon then, nitrogen replacement, hydrogen exchange keeps 2 atm pressure then, and stirring reaction filters, and concentrates, and gets the Cucurbitacin E verivate of said formula XV.
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Cited By (6)
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| CN103804451A (en) * | 2012-11-14 | 2014-05-21 | 沈阳药科大学 | Method for preparing cucurbitacine D by hydrolyzing cucurbitacine B |
| CN104892713A (en) * | 2015-04-16 | 2015-09-09 | 中国农业科学院蔬菜花卉研究所 | Preparation method and applications of cucurbitacin C and analogs thereof |
| CN107857789A (en) * | 2017-12-15 | 2018-03-30 | 张南 | Cucurbitacin derivatives and preparation method thereof |
| CN110041392A (en) * | 2019-02-27 | 2019-07-23 | 浙江工业大学 | A kind of preparation method of cucurbitacin D |
| CN115414369A (en) * | 2022-08-30 | 2022-12-02 | 中国农业大学 | Application of cucurbitacin C in preparation of medicine for preventing or treating inflammatory bowel disease |
| WO2023169372A1 (en) * | 2022-03-09 | 2023-09-14 | 中国科学院上海药物研究所 | Cucurbitacin b derivative, preparation method therefor, and use thereof |
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| CN110590892B (en) * | 2019-09-29 | 2021-06-22 | 南京中医药大学 | Triterpene compound with anti-tumor activity separated from waste fructus Trichosanthis pulp and its application |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804451A (en) * | 2012-11-14 | 2014-05-21 | 沈阳药科大学 | Method for preparing cucurbitacine D by hydrolyzing cucurbitacine B |
| CN104892713A (en) * | 2015-04-16 | 2015-09-09 | 中国农业科学院蔬菜花卉研究所 | Preparation method and applications of cucurbitacin C and analogs thereof |
| CN107857789A (en) * | 2017-12-15 | 2018-03-30 | 张南 | Cucurbitacin derivatives and preparation method thereof |
| WO2019114525A1 (en) * | 2017-12-15 | 2019-06-20 | 张南 | Cucurbitacin derivative and preparation method therefor |
| CN110041392A (en) * | 2019-02-27 | 2019-07-23 | 浙江工业大学 | A kind of preparation method of cucurbitacin D |
| WO2023169372A1 (en) * | 2022-03-09 | 2023-09-14 | 中国科学院上海药物研究所 | Cucurbitacin b derivative, preparation method therefor, and use thereof |
| CN115414369A (en) * | 2022-08-30 | 2022-12-02 | 中国农业大学 | Application of cucurbitacin C in preparation of medicine for preventing or treating inflammatory bowel disease |
| CN115414369B (en) * | 2022-08-30 | 2023-09-15 | 中国农业大学 | Application of cucurbitacin C in preparation of medicines for preventing or treating inflammatory bowel disease |
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