LU503660B1 - Method for synthesizing quercetin ester by one-pot, products and application thereof - Google Patents

Method for synthesizing quercetin ester by one-pot, products and application thereof Download PDF

Info

Publication number
LU503660B1
LU503660B1 LU503660A LU503660A LU503660B1 LU 503660 B1 LU503660 B1 LU 503660B1 LU 503660 A LU503660 A LU 503660A LU 503660 A LU503660 A LU 503660A LU 503660 B1 LU503660 B1 LU 503660B1
Authority
LU
Luxembourg
Prior art keywords
anhydride
quercetin
chloride
ester
pot
Prior art date
Application number
LU503660A
Other languages
English (en)
Inventor
Zhongyan Cao
Original Assignee
Univ Henan
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Henan filed Critical Univ Henan
Priority to LU503660A priority Critical patent/LU503660B1/fr
Application granted granted Critical
Publication of LU503660B1 publication Critical patent/LU503660B1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Saccharide Compounds (AREA)

Abstract

The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing quercetin ester by one-pot, products and applications thereof. Rutin is reacted with anhydride or acyl chloride, boiled in one pot under the action of acid or alkali, and then directly prepared into quercetin ester by ultrasonic at the power of 300W for 50min. The invention provides a plurality of new quercetin ester compounds which are synthesized by a one-pot method. The method has the advantages of easily available reagents, mild conditions, few operation steps, labor and time saving, raw materials saving, less emission pollution and high yield, which lays a foundation for the effective utilization of quercetin derivatives and has popularization value.

Description

DESCRIPTION LU503660
METHOD FOR SYNTHESIZING QUERCETIN ESTER BY ONE-POT, PRODUCTS
AND APPLICATION THEREOF
TECHNICAL FIELD
The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing quercetin ester by one-pot, products and applications thereof.
BACKGROUND
Quercetin (3,4',3',5,7- pentahydroxyflavone) is a typical flavonoid, which exists in many foods such as apples, onions, broccoli, grapes, ginkgo biloba, tea and so on.
Quercetin has many physiological activities, such as anti-cancer, blood-lowering, anti-virus, prevention and treatment of cardiovascular and cerebrovascular diseases, anti-inflammatory and anti-oxidation. Epidemiologists and nutritionists believe that quercetin is a natural compound with the most promising application in the prevention and treatment of diseases. The molecular structure of quercetin makes it poor in water solubility and low in bioavailability. In order to improve this situation, many quercetin metal complexes and quercetin esters with good water solubility and high bioavailability have been prepared. For example, quercetin glutamic acid and quercetin alanine ester were synthesized by Tahsin, which can be used as the most effective conjugate to inhibit cell growth and have a good inhibitory effect on prostate cancer cells (TAHSIN F K,
MARIA V C, MIN-SUNG L E, et al. Rational design and structure-activity relationship studies of quercetin-amino acid hybrids targeting the anti-apoptotic protein Bcl-xL[J].
Org. Biomol. Chem., 2017, 15(37): 7956-7976.). Quercetin -3-O- phenyl isocyanate was synthesized by Ye Bin et al. It has good inhibitory effects on human chronic bone marrow leukemia cell K562(/Cs50=1.852umol/L) and mouse colon cancer cell
CT26(/Cs0=1.177pmol/L), which are 73 times and 308 times higher than quercetihJ503660 respectively (YE Bin, YANG Jin-liang, CHEN Li-juan, et al. Induction of apoptosis by phenylisocyanate derivative of quercetin: involvement of heat shock protein[J].
Anti-Cancer Drugs, 2007, 18 (10): 1165-1171.). Hirpara, Ketan V. Studies show that molecules from plants play an important role in cancer chemotherapy. Flavonoid quercetin, a plant-derived molecule, has been shown to regulate proliferation and cause cancer cell death. Some flavonoids have entered clinical trials, among which quercetin has emerged as a prospective anticancer drug candidate, and its prodrug quercetin -3- amino acid ester (QC12) has entered phase | clinical research (Hirpara, Ketan V.;
Aggarwal, Pawan; Mukherjee, Amrita J.;et al. Quercetin and Its Derivatives: Synthesis,
Pharmacological Uses with Special Emphasis on Anti-Tumor Properties and Prodrug with Enhanced Bio-Availability, Anti-Cancer Agents in Medicinal Chemistry (Formerly
Current Medicinal Chemistry - Anti-Cancer Agents), 2009 ,9(2): 138-161.). Ekta Kohli and other experiments found that quercetin pentaacetate (QPA) can inhibit the genotoxicity of aflatoxin B1(AFB1). The function of QPA leads to the regulation of some enzymes (such as P-450 enzyme, catalytic activity of NADPH) through microsomal transacetylase, and cytochrome C reductase and glutathione S- transferase may be acetylated through protein. Unlike quercetin, QPA can be observed to inhibit the binding of AFB1 to DNA. Explain the role of QPA in preventing genetic toxicity caused by AFB1 (Ekta Kohli, Hanumantharao G. Raj, Ranju Kumari, et al. Comparison of the Prevention of Aflatoxin B1-Induced Genotoxicity by Quercetin and Quercetin Pentaacetate,
Bioorganic & Medicinal Chemistry Letters 2002,12 : 2579-2582). ZHANG Yihua et al. synthesized 3, 3', 4', 5- tetra -O- acylated quercetin, and synthesized 3, 3', 4', 5- tetra -O- acetylated quercetin and 3, 3', 4', 5- tetra -O- propionylated quercetin respectively (CN 105693677 A, Application date: 2016.03.01).
Quercetin esters have good pharmacological activities, some of which have significant inhibitory effects on cancer cells, while others have strong free radical scavenging ability, which provides important clues for the effective utilization of natural compounds. There are many reports on quercetin monoacyl ester compounds, but few on quercetin diacyl ester compounds, quercetin triacyl ester compounds and quercetin tetraacyl ester compounds. At present, only quercetin pentaacetate is reported drJ503660 quercetin pentaacyl ester compounds. In addition, the conventional method of synthesizing quercetin ester is as follows: rutin is hydrolyzed in methanol hydrochloric acid solution, and quercetin is obtained by separation. Quercetin is esterified with anhydride or acyl chloride under the action of concentrated sulfuric acid to obtain quercetin ester.
LAOH es 0
HO LA x A ~, & 2 Je HO. I LA, PX 8 H | ET Toe CHOR, HO . RC [ § | Oo © SE So. = I CE OH
Au 3 “Ruin sugar nu à
ROCO. LA 102 8 A
Sn Np” eT he FT TN ym a (RODS RCOCH . HST \ | | OCOR
EEE nu bee, ab AL
FAN YT Y COR
ROGO D
The disadvantages of this method are that the hydrolysis of rutin needs to consume a lot of methanol, and it is difficult to separate methanol from water to form an azeotrope, and the discharge of acid-containing wastewater seriously pollutes the environment. The cost of products obtained by rutin hydrolysis and quercetin esterification is relatively high.
SUMMARY LU503660
The purpose of the invention is to provide a method for synthesizing quercetin ester by one-pot, its product and application.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
The invention relates to a method for synthesizing quercetin ester by one-pot boiling, which comprises the following steps: reacting rutin with anhydride or acyl chloride, boiling in one pot under the action of acid or alkali, and then directly preparing quercetin ester by ultrasonic at the power of 300W for 50 minutes; the general structural formula of the quercetin ester is as follows: where the R substituents can be the same or different from the following substituents: methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, phenyl, benzyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-ethylphenyl, m-ethylphenyl, p-ethylphenyl, o-nitrophenyl, m-hydroxyphenyl, p-chlorophenyl, p-bromophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl.
The acid anhydride is aliphatic acid anhydride or aromatic acid anhydride.
The aliphatic anhydride can be acetic anhydride, propionic anhydride, butyric anhydride, succinic anhydride or butyric anhydride; The aromatic anhydride is benzoic anhydride, phenylacetic anhydride, o-methylbenzoic anhydride, p-methylbenzoic anhydride, o-chlorobenzoic anhydride or p-chlorobenzoic anhydride.
The acyl chloride is preferably selected from one of the following: acetyl chloride, propionyl chloride, butyryl chloride, benzoyl chloride, phenylacetyl chloride, o-methylbenzoyl chloride, m-methylbenzoyl chloride, p-methylbenzoyl chloride, and o-chlorobenzoyl chloride.
The acid is sulfuric acid and hydrochloric acid, and the base is aniline, piperidine 6503660 pyridine. Generally, acid is used as catalyst for the reaction of rutin with acid anhydride, and alkali is used as catalyst for the reaction of rutin with acyl chloride.
The feeding ratio is: rutin: anhydride or acyl chloride: acid or alkali = 1 mol: 1-10 ml: 0.05-1 ml.
The reaction temperature is controlled at 25-98°C, and stirring is carried out during the reaction. Heating can be done by electric heating jacket, microwave heating, water bath or oil bath.
Rutin can be dissolved in a solvent before reaction, and the solvent is not particularly required, so long as rutin can be dissolved.
Quercetin ester is generally prepared by the reaction of quercetin with anhydride or acyl chloride, and quercetin is prepared by the hydrolysis of rutin. In the invention, rutin reacts with anhydride or acyl chloride, and quercetin ester is directly prepared by one-pot boiling. In this method, rutin reacts with anhydride or acyl chloride under the action of acid or base (piperidine), and rutin tetraester is generated at first. At the same time of reaction, rutin glycosidic bond is broken under the action of by-product hydrogen chloride, and exposed quercetin 3- hydroxyl group further reacts with anhydride or acyl chloride to generate quercetin pentaester.
AH OCOR
HOU A 50: (X ROCO 0 C 0 |. Dé (RCOHÔ or RCOC O | Le
YY Nn gr Acid or base QCOR
OH © ROCO ©
The one-pot cooking method of the invention has the advantages of easily available reagents, mild conditions, few operation steps, labor and time saving, raw materials saving, emission reduction, less pollution and high yield, which lays a foundation for the effective utilization of quercetin derivatives, is a method with great popularization value, and conforms to the principle of sustainable development according to the principle of atomic economy.
According to the different raw materials used, many different compounds can B&J503660 synthesized. The following 2-13 are new compounds that have never been reported before:
ACOH; 27, SCOCHCHS
OOOH. A 01 A HCHCOCHO, oO. AL A
Pood OY Y Sooo, TEN 1 7 ococHcH,
V4 ocook, YT ET OCOCHCH, 40000 0 HORCO00 Ù
Quercetin pentaacetate (3} M: 512 Quercetin pentapropionate (23 M:582 (FN ACCCgH A DOCH CH
CH DCHO 2 A. A I 0-H; CE OCHO. A a ) mi vf x x Fe GOOCH; AR N N ae” GLOC:HAH-0 oy Y SOCOGH Y Ÿ OCOC:H.CH20 i i ; ! 3
CHO ö CC 9
Quercetin pentabenzoate (3) M:822 Quercetin pentao-toiuic acid ester (43 M:892 25, OCOC HE Hz „A FOGG
CO OCHO = 0 A | HOCH OCHO. PA 0 À
A-HACC/HOCHD PR DE Peg ha wT NR Nee 1 w À À Nt Cr ys Y “OCOCHCHm j I QCOGHCHD i ; CPAS £ aHEO HO à pHCCHOC0 0
Quercetin pentam-metlw! benzoate (5) M802 Quercetin pentap-methyl berzoate (6) M:592
LÉ ECOCHACH2}y5,5-4 AE ii oso A 0 2 0 PHCHOCHOCHO o_O A À
CGR AE 1 T u COOH SE C | y } SAN
SO SE py
NY O00CH C35 TY Teen wh d-5-3{Hk;Ch0H;000 à PHAHLGHOC0 D
Quercetin penta (3, 5-dimethylbenzoie acid} ester {7} M:062 Quercetin pentaethy! benzoate (8) M862
The antitumor activities of the above compounds were tested, and all of them had good antitumor activities.
Compared with the prior art, the invention has the following advantages:
The invention provides a plurality of new quercetin ester compounds which are synthesized by a one-pot method. The method has the advantages of easily available reagents, mild conditions, few operation steps, labor and time saving, raw material$J503660 saving, emission reduction, less pollution and high yield, which lays a foundation for the effective utilization of quercetin derivatives, is a method with great popularization value, and conforms to the principle of sustainable development according to the principle of atomic economy.
BRIEF DESCRIPTION OF THE FIGURES
Fig. 1 shows a flow chart of conventional synthesis process of quercetin ester
Fig. 2 shows a process flow chart of one-pot synthesis of quercetin ester
DESCRIPTION OF THE INVENTION
The following describes the technical scheme of the present invention with specific examples, but the protection scope of the present invention is not limited to this:
In the following examples, the amount of acid or base catalyst is expressed in drops, and the volume of 20 drops is 1ml.
Example 1
Synthesis of quercetin pentaacetate (1)
Weigh 610mg (1mmol) of rutin, add 5ml of acetic anhydride, stir for 0.5h with a magnetic stirrer, add 5 drops of concentrated sulfuric acid, control the temperature at 65°C, reflux for 6h, monitor the reaction progress with TLC plate, add 80mI of distilled water, stir for 2h, then after ultrasonic treatment at 300W for 50min, a large number of solids will precipitate until the solids precipitate and water become clear, discard the water layer, and wash the precipitate to neutrality. Adding 80mL of ethyl acetate to dissolve, passing through silica gel column, eluting with acetone: petroleum ether (3:2), collecting eluate, rotary steaming, and recrystallizing with chloroform/methanol, with a yield of 58.2%.
Colorless crystal, m. p. 194.5-195.1°C (literature value: 195-196°C). IR (KBr),nv, em”: 2946.2, 1776.3, 1264.6, 1199.82. "HNMR (DMSO, 600MHz), à: 7.86 (m, 1H, 2-H); 7.84
(m, 1H, 6'-H); 7.65 (s, 1H, 5'H); 7.55 (s, 1H, 8H); 6.17 (s, 1H, 6H); 2.34 (m, 15H, CHAU503660
MS, m/z: 513.1[M+1]*.
Example 2
Synthesis of quercetin pentapropionate (2)
Weigh 610mg(1mmol) of rutin, add 5ml of propionic anhydride, stir it with a magnetic stirrer for 0.5h, then add 5 drops of concentrated sulfuric acid, control the temperature at 65°C, reflux for 6h, monitor the reaction progress with TLC plate, add 80mI of distilled water, stir for 2h, then after ultrasonic treatment at 300W for 50min, a large number of solids will precipitate until the solids precipitate and water become clear, and the precipitate will be washed to neutrality; adding 80mL of ethyl acetate to dissolve, passing through silica gel column, eluting with acetone: petroleum ether (3:2), collecting eluate, rotary steaming, and recrystallizing with chloroform/methanol. The yield is 57.3%. m. p.136.1-138.4 °C. IR (KBr), v, cm: 2936, 1769.2, 1244.6, 1108.8. "HNMR (CDCls, 600MHz), à: 7.86 (m, 1H, 2-H); 7.64 (m, 1H, 6-H); 7.60 (s, 1H, 5' H); 7.54 (s, 1H, 8H); 7.16 (s, 1H, 6H); 2.63-2.78 (d, 10H, CH); 1.16 (m, 15H, CHz). MS, m/z: 583.18[M+1]*.
Example 3
Synthesis of quercetin pentabenzoate (3)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of benzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 10 drops of piperidine, control the temperature at 65°C, reflux for 6h, monitor the reaction progress with TLC plate, add 80ml of distilled water, stir for 2h, and then ultrasonic at 300W for 50min, and a large number of solids will precipitate. The water layer was discarded until the solid was precipitated and the water became clear. The precipitate was washed with water until it was neutral, and 80mL of ethyl acetate was added to dissolve it. After passing through a silica gel column, acetone: petroleum ether (3:2) was eluted, and the eluent was collected for rotary evaporation. After recrystallization with chloroform/methanol, the yield was 57.3%, m. p. 112.3-1114.5°C. IR (KBr), v, cm”: 3406.0, 2926.1, 1745.3, 1259.6, 1129.8. "HNMR (CDCIs, 600MHz), à: 7.78 (m, 1H, 2'-H); 7.72 (m, 1H, 6'-H); 7.70 (s, 1H, 5'H); 7.66 (s, 1H, 6H); 6.17 (s, 1H, 8H); 7.62-8.04 (m, 25H, ph-H). MS, m/z: 823.18[M+1]*.
Example 4 LU503660
Synthesis of quercetin pentao-toluic acid ester (4)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of o-methylbenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 6 drops of piperidine, control the temperature at 55°C, reflux it for Sh, monitor the reaction progress by TLC plate, add 80mI of distilled water, stir it for 2h, and then a large number of solids precipitate after ultrasonic treatment for 50min at 300W W. When the solid is precipitated and the water becomes clear, the water layer is discarded, and the precipitate is washed with water until it is neutral, then 80mL of methyl acetate is added to dissolve it, and it passes through a silica gel column, and acetone: petroleum ether (3:1) is eluted, and the eluent is collected for rotary evaporation and recrystallized by chloroform/methanol to obtain a white solid with a yield of 68.1%, m.p.118.6-119.8°C. IR (KBr), v, cm”: 3406.4, 2840.2, 1668.0, 1246.7, 1139.7. "HNMR (CDCIs, 600MHz), à: 8.20 (s, 1H, 2-H); 7.87 (m, 1H, 6-H); 7.76 (m, 1H, 5'H); 7.62 (s, 1H, 6H); 7.35 (m, 1H, 8H); 7.18-7.40 (m, 20H, ph-H); 2.20-2.84 (s, 15H, CHz). MS, m/z: 893.4[M+1]*.
Example 5
Synthesis of quercetin pentam-methyl benzoate (5)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of m-methylbenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 8 drops of piperidine, control the temperature at 60°C, reflux for 6h, monitor the reaction progress with TLC plate, add 80mI of distilled water, stir for 2h, and then a large number of solids precipitate after ultrasonic treatment for 50min at 300W W. When the solid is precipitated and the water becomes clear, the water layer is discarded, and the precipitate is washed with water until it is neutral. Then, 80mL of n-propyl acetate is added to dissolve it, and it is eluted by silica gel column and acetone: petroleum ether (2:2), and the eluent is collected for rotary evaporation, and then it is recrystallized by chloroform/methanol to obtain a white solid with a yield of 54.4%, m. p. 121.1-123.6°C. IR (KBr), v, cm”: 3414.8, 2907.3, 1775.4, 1286.8, 1068.7. "HNMR (CDCIs, 600MHz), 8.27 (s, 1H, 2-H, ph-H); 8.17 (m, 1H, 6-H, ph-H); 8.03 (s, 1H, 5'H); 7.61 (s, 1H, 6H); 7.45 (s, 1H, 8H); 7.36-7.79 (m, 20H, ph-H); 2.07-2.83 (s, 15H, CHz). MS, m/z: 893.3[M+1]*.
Example 6 LU503660
Synthesis of quercetin penta-p-methyl benzoate (6)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of p-toluoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 7 drops of piperidine, control the temperature at 50°C, reflux it for 5h, monitor the reaction progress with TLC plate, add 80ml of distilled water, stir it for 2h, and then a large number of solids precipitate after ultrasonic treatment for 50min at 300W W. When the solid is precipitated and the water becomes clear, the water layer is discarded, the precipitate is washed with water to neutrality, 70mL of methyl acetate is added for dissolution, and then eluted by silica gel column and acetone: petroleum ether (3:2.5), and the eluent is collected for rotary evaporation, and then recrystallized by chloroform/methanol to obtain a white solid with a yield of 43.8%, m. p. 126.3-127.5°C. IR(KBr), v, cm": 3308.2, 2897.3, 1738.9, 1328.4, 1029.6. "HNMR (CDCIs, 600MHz), à: 7.86 (m, 1H, 2-H); 7.65 (m, 1H, 6-H); 7.55 (s, 1H, 5'H); 7.52 (s, 1H, 6H); 7.17 (s, 1H, 8H); 7.14-7.83 (m, 20H, ph-H); 2.39-2.65 (s, 15H, CHz). MS, m/z: 893.3[M+1]*.
Example 7
Synthesis of quercetin penta (3,5- dimethyl) benzoate (7)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add ml of 3,5-dimethylbenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 10 drops of piperidine, control the temperature at 58°C, reflux for 4h, monitor the reaction progress by TLC plate to ensure the complete reaction, add 80ml of distilled water, stir for 2h, Then, after ultrasonic treatment for 50min at a power of 300W, a large number of solids were precipitated until the solids were precipitated and the water became clear and the water layer was discarded. The precipitate was washed with water until it was neutral, and 65mL of methyl acetate was added to dissolve it. After passing through a silica gel column, ethyl acetate: dichloromethane (3:2) was eluted, and the eluent was collected for rotary evaporation. After recrystallization by chloroform/methanol, a white solid was obtained with a yield of 61.1%, m. p. 132.6-133.1°C. IR(KBr), v, cm: 3518.2, 2802.6, 1721.8, 1259.7, 1129.6. "HNMR (CDCl, 600MHz), à: 7.91 (s, 1H, 2'-H); 7.78 (m,
1H, 6'-H); 7.58 (s, 1H, 5'H); 7.43 (s, 1H, 6H); 7.26 (s, 1H, 8H); 7.25-7.67 (m, 15H, ph-H)U503660 2.17-2.35 (s, 30H, CHz). MS, m/z: 963.5[M+1]*.
Example 8
Synthesis of quercetin pentaethyl benzoate (8)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of p-ethylbenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 12 drops of piperidine, control the temperature at 62°C, reflux for 4h, monitor the reaction progress by TLC plate to ensure the complete reaction, add 80mI of distilled water, stir for 2h,
Then, after ultrasonic treatment for 50min at a power of 300W, a large number of solids were precipitated until the solids were precipitated and the water became clear and the water layer was discarded. The precipitate was washed with water until it was neutral, and 82mL of ethyl acetate was added for dissolution. After passing through a silica gel column, ethyl acetate: dichloromethane (3:1) was eluted, and the eluent was collected for rotary evaporation. After recrystallization by chloroform/methanol, a white solid was obtained with a yield of 63.4%, m. p. 130.1-131.6°C. IR(KBr), v, cm": 3416.3, 2901.2, 1725.3, 1248.8, 1069.8. "HNMR (CDCIs, 600MHz), à: 7.79 (m, 1H, 2-H); 7.76 (m, 1H, 6-H); 7.74 (s, 1H, 5'H); 7.66 (s, 1H, 6H); 6.17 (s, 1H, 8H); 7.25-7.67 (m, 20H, ph-H); 2.27-2.52 (s, 15H, CHz); 0.97-1.08 (m, 10H, CH). MS, m/z: 963.2[M+1]*.
Example 9
Synthesis of quercetin pentaphenylacetate (9)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of phenylacetyl chloride, stir it with a magnetic stirrer for 0.5h, then add 9 drops of piperidine, control the temperature at 57°C, reflux for 4h, monitor the reaction progress by TLC plate, add 80ml of distilled water, stir for 2h, and then ultrasonic at 300W for 50min, and a large number of solids will precipitate. Discard the water layer until the solid is precipitated and the water becomes clear, wash the precipitate with water until it is neutral, add 68mL of methyl acetate to dissolve it, pass through a silica gel column, elute with ethyl acetate and dichloromethane (2:3), collect the eluent, and evaporate it by rotary evaporation, and recrystallize it with chloroform/methanol to obtain a white solid with a yield of 60.5%, m. p. 129.5-130.2°C. IR(KBr), v, cm”: 3446.8, 2922.8, 1725.3,
1237.4, 1057.6. 'HNMR (CDCIs, 600MHz), à: 7.78 (m, 1H, 2'-H); 7.75 (m, 1H, 6'-H); 7.74J503660 (s, 1H, 5'H); 7.61 (s, 1H, 6H); 6.19 (s, 1H, 8H); 7.26-7.69 (m, 25H, ph-H); 0.98-1.09 (m, 10H, CHz). MS, m/z: 893.4[M+1]*.
Example 10
Synthesis of quercetin pentao-chlorobenzoic acid ester (10)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of o-chlorobenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 12 drops of piperidine, control the temperature at 75°C, reflux for 4h, and monitor the reaction progress by TLC plate to ensure the complete reaction. Adding 80ml distilled water, stirring for 2 hours, and then ultrasonic for 50min minutes at a power of 300W, a large number of solids were precipitated. When the solid is precipitated and the water becomes clear, the water layer is discarded, and the precipitate is washed with water until it is neutral, and 68mL of ethyl acetate is added to dissolve it, then it passes through a silica gel column, methyl acetate: dichloromethane (3:2) is eluted, and the eluent is collected for rotary evaporation, and then it is recrystallized by chloroform/methanol to obtain a white solid with a yield of 58.8%, m. p. 132.6-133.1°C. IR(KBr), v, cm: 3408.7, 1663.1, 1168.9, 1014.7. "HNMR (CDCIs, 600MHz), à: 8.25 (m, 1H, 2'-H); 8.15 (m, 1H, 6'-H); 8.08 (s, 1H, 5'H); 8.01 (s, 1H, 6H); 7.50 (s, 1H, 8H); 7.01-7.90 (m, 20H, ph-H). MS, m/z: 995.1[M+1]*.
Example 11
Synthesis of Quercetin Pentachlorobenzoate (11)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5ml of p-chlorobenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 11 drops of piperidine, control the temperature at 74°C, reflux for 4h, monitor the reaction progress with TLC plate to ensure that the reaction is complete, add 80mI of distilled water, stir for 2h, and after ultrasonic treatment for 50min at 300W, a large amount of solids will be produced. Discard the water layer until the solid is precipitated and the water becomes clear, wash the precipitate with water until it is neutral, add 78mL of ethyl acetate to dissolve it, pass through a silica gel column, elute with methyl acetate: dichloromethane (3:1), collect the eluent, and evaporate it by rotary evaporation, and recrystallize it with chloroform/methanol to obtain a white solid with a yield of 61.3%, m. p. 132.6-134.1°CU503660
IR(KBr), v, cm‘: 3436.2, 1785.2, 1247.9, 1019.4. "HNMR (CDCIs, 600MHz), & 8.19 (m, 1H, 2-H); 7.84 (s, 1H, 6-H); 7.52 (m, 1H, 5H); 7.47 (s, 1H, 6H); 7.25 (s, 1H, 8H); 7.18-7.90 (m, 20H, ph-H). MS, m/z: 955.2[M+1]*.
Example 12
Synthesis of quercetin penta (2,3-dichlorobenzoic acid) ester (12)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add ml of 2,3-dichlorobenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 15 drops of piperidine, control the temperature at 78°C, reflux for 4h, and monitor the reaction progress by TLC plate to ensure the complete reaction. Adding 80ml distilled water, stirring for 2 hours, and then ultrasonic for 50min minutes at a power of 300W, a large number of solids were precipitated. When the solid is precipitated and the water becomes clear, the water layer is discarded, and the precipitate is washed with water to be neutral, then 70mL of ethyl acetate is added to dissolve it, and it passes through a silica gel column, and methyl acetate: dichloromethane (2:3) is eluted, and the eluent is collected for rotary evaporation and recrystallized by chloroform/methanol to obtain a white solid with a yield of 52.4%, m. p. 137.6°C. IR(KBr), v, cm”: 3466.1, 1794.2, 1347.6, 1121.6. "HNMR (CDCIs, 600MHz), à: 8.33 (m, 1H, 2-H); 8.17 (m, 1H, 6-H); 7.83 (s, 1H, 5H); 7.55 (s, 1H, 6H), 7.20 (s, 1H, 8H), 7.30-7.93 (m, 15H, ph-H). MS, m/z: 1169.0[M+1]*.
Example 13
Synthesis of quercetin penta (3,4-dichlorobenzoic acid) ester (13)
Weigh 610mg(1mmol) of rutin, dissolve it in 20ml of dimethylformamide (DMF), add 5 ml of 3,4-dichlorobenzoyl chloride, stir it with a magnetic stirrer for 0.5h, then add 14 drops of piperidine, control the temperature at 77°C, reflux for 4h, and monitor the reaction progress by TLC plate to ensure the complete reaction. Adding 80ml distilled water, stirring for 2 hours, and then ultrasonic for 50min minutes at a power of 300W, a large number of solids were precipitated. Discard the water layer until the solid is precipitated and the water becomes clear, wash the precipitate with water until it is neutral, add 70mL of ethyl acetate to dissolve it, pass through a silica gel column, elute with methyl acetate: dichloromethane (3:1.5), collect the eluate, and evaporate it kyJ503660 rotary evaporation, and recrystallize it with chloroform/methanol to obtain a white solid with a yield of 51.6%, m. p. 132.6-133.1°C. IR(KBr), v, cm”: 3370.2, 1791.7, 1233.9, 1011.3. 'THNMR (CDCIs, 600MHz), à: 7.79 (m, 1H, 2'-H); 7.76 (m, 1H, 6-H); 7.74 (s, 1H, 5'H); 7.66 (s, 1H, 6H); 6.17 (s, 1H, 8H); 7.25-7.67 (m, 15H, ph-H). MS, m/z: 1166.9[M+1]
Anti-tumor activity experiment
MTT assay was used to detect the inhibitory effects of quercetin and its esters at different concentrations on the proliferation of EC109 cells, EC9706 cells, B16-F10 cells and SGC-7901 cells. Logarithmic growth cells were collected, and the concentration was adjusted to 6x10° cells/well, and inoculated into 96-well culture plates, with 200uL per well. 5% CO», saturated humidity and 37°C incubator. When the cells adhered to the wall, the final concentration of quercetin diluted with RPMI1640 medium was 0.5, 1, 2, 4, 8, 16, 32, 64 and 128 pg/mL in the experimental group, and the complete medium was added in the solvent control group, with the final volume of each well being 200 uL, and each group was provided with 6 multiple wells. After 72 h of culture, the culture plate was taken out, and the morphology was observed under the inverted microscope and photographed. Then add 5 mg/mL MTT (20 uL/ well) to continue the culture for 4 h, pour out the original culture solution, then wash each well with PBS, add DMSO (150 uL/ well), shake well to dissolve the precipitate, and after 20 min at room temperature (magenta solution), detect the light absorption value (A value) of each well at 570 nm on an enzyme-linked immunosorbent assay. The experiment was repeated independently for 3 times, and the average value was taken, and the growth inhibition rate was calculated according to formula (1). According to the obtained results, the /Cso value is calculated by using SPPS19.0.
Gl! (growth inhibition rate) = 1- (A value of drug group/A value of control group) x100%, the antitumor activities of 13 quercetin esters and quercetin were preliminarily evaluated by MTT assay. Taking fluorouracil as the positive control, the inhibitory effects of the target compound on human esophageal squamous cell carcinoma (EC109),
human esophageal squamous cell carcinoma (EC9706), human gastric cancer célU503660 (SGC7901) and mouse melanoma cell (B16-F10) were investigated respectively.
As can be seen from Table 1, quercetin has relatively good inhibitory effects on
EC109 and EC9706 cells, while the /Cso values of the other two cells are both greater than 128 pmol/L. Thirteen kinds of quercetin ester derivatives synthesized have different degrees of inhibitory effects on these four cancer cells, and quercetin pentachlorophenate has good inhibitory effects on human esophageal squamous cell carcinoma (EC109) and human esophageal squamous cell carcinoma (EC9706).
Table 1 Proliferation inhibition rate of quercetin ester on different tumor cells (SD)
/Cso/ (umol-L"*)
EC109 EC9706
Serial Human Human SGC7901
Compound B16-F10 numb esophageal esophageal Human a Mouse er squamous squamous gastric melanoma cell cell cancer carcinoma carcinoma 29.182+1.41 193.444+1.62 115.18+1.83 1 CHz- 68.845+1.175 7 8 0 64.142+1.57 271.835+2.1 2 CH3CHz- 56.23+1.931 61.957+1.635 3 44 55.361+1.28 113.284+1.68 186.352+1.62 153.294+1.3 3 OO 4 2 7 46
H 86.356+1.75 108.397+1.62 189.391+1.53 98.267+1.38 4 as 8 1 1 0 128.367+1.2 162.591+1.65 138.362+1.2 84.576+1.197
H 13 9 56
H + — 46.274+1.39 129.312+1.69 110.613+1.24 83.612+1.29 6 7 0 7 1
HsH 59.618+1.25 114.326+1.27 127.291+1.5 7 91.503+1.153
HoH 0 1 70 101.153+1.1 218.187+2.1 8 : A) 51.62+1.168 61.523+1.231 26 16 57.086+1.17 63.897+1.138 125.314+1.13 82.542+1.26 0H 3 4 7 77.820+1.05 46.287+1.348 81.169+1.192 69.324+1.12
Oo - 11 —~ 28.446+1.62 26.562+1.267 87.691+1.651 79.318+1.57
2 LU503660 a 47.041+1.74 127.264+1.19 102.328+1.1 12 a 96.167+1.138 0 4 62 81.259+1.26 121.328+1.18 92.165+1.51 13 | ) 3 82.271+1.160 8 6 6 31.924+0.68 125.183+1.24 191.357+1.73 14 Quercetin - 4 4 5 41.738+0.73 182.115+1.3 5-FU 78.431+1.008 62.562+0.910 4 74
The /Cso values of quercetin pentachlorobenzoate on human esophageal squamous cell carcinoma (EC109) reached 28.446 pmol/L, which was far less than that of quercetin (31.924 pmol/L) and better than that of 5-FU (41.738 umol/L), and it is expected to be a candidate drug for esophageal squamous cell carcinoma. In addition, other compounds showed certain inhibitory effects on four kinds of cancer cells.

Claims (9)

CLAIMS LU503660
1. A method for synthesizing quercetin ester by one-pot, characterized by comprising: reacting rutin with anhydride or acyl chloride, boiling in one pot under the action of acid or alkali, and then directly preparing quercetin ester by ultrasonic at a power of 300W for 50min; the general structural formula of the quercetin ester is as follows: where the R substituents can be the same or different from the following substituents: methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, phenyl, benzyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-ethylphenyl, m-ethylphenyl, p-ethylphenyl, o-nitrophenyl, m-hydroxyphenyl, p-chlorophenyl, p-bromophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl.
2. The method for synthesizing quercetin ester by one-pot according to claim 1, wherein the anhydride is aliphatic anhydride or aromatic anhydride.
3. The method for synthesizing quercetin ester by one-pot according to claim 1, wherein the aliphatic anhydride is acetic anhydride, propionic anhydride, butyric anhydride, succinic anhydride or maleic anhydride, and the aromatic anhydride is benzoic anhydride, phenylacetic anhydride, o-toluic acid anhydride, p-toluic anhydride, o-chlorobenzoic anhydride or p-chlorobenzoic anhydride.
4. The method for synthesizing quercetin ester by one-pot according to claim 1, wherein the acyl chloride is acetyl chloride, propionyl chloride, butyryl chloride, benzoyl chloride, phenylacetyl chloride, o-methylbenzoyl chloride, m-methylbenzoyl chloride, p-methylbenzoyl chloride or o-chlorobenzoyl chloride.
5. The method for synthesizing quercetin ester by one-pot according to claim LU503660 wherein the feeding ratio is: rutin: anhydride or acyl chloride: acid or alkali = 1mol: 1-10ml: 0.05-1ml.
6. The method for synthesizing quercetin ester by one-pot according to claim 1, wherein the acid is sulfuric acid and hydrochloric acid, and the base is aniline, piperidine or pyridine.
7. The method for synthesizing quercetin ester by one-pot according to claim 1, wherein the reaction temperature is controlled at 25-98°C, and stirring is carried out during the reaction.
8. Quercetin ester synthesized by one-pot according to any one of claims 1 to 7, wherein a structural formula of the quercetin ester is shown as follows: 7 OOOO 30 3 CO 0000; 3
O. 3000 © € O. | 0000 40 3 Os 300 ©. J | 0000s 3 OOOO 30 3 00003 3 30 30000 Ö O3 3000 oO 00003 O 3 eu O 3m
O. 3003 hg N San m 300; “0 | 0000; O 3m 00003 O 3 00003 O 3m 3003 000 0 m 3003 OOO Ô 7 0000; © 33 en 30 À3 333 O O 3 3003 OO O J | 0000; O 33 3 3 3( 30(303 300 0 | b000s AO 43333 00003 O 33 1) 90008 MO 48333 3 3003 000 O 3 3 3( 30(303 3000 O OOOO3 30 30 33 © OOOO 303 3
O. 3 30 3003 OO ie O. | en 04033 O3 3 3000 O ©) | 0000 30s 3 0000; O 30 33 0000 303 3 3 30 300; 000 © Os 3 30000 O 0000; 30 OS 30 3 O 00; "0 © | J ° 300s “0 | 0000; O3 0000; O 00003 O3 003 000 Ô 3003 OOO Ô O O3 3033 3 CO 3 3 3030; 5 O 0) Lens se | O O3 3035 3 O O3 3033 3 O 0, 305 3 3 3003 5 O 3 O 303 3 O
9. Application of quercetin ester according to claim 8 in antineoplastic drugs.
PATENTANSPRÜCHE LU503660
1. Ein Verfahren zur Synthese von Quercetinester durch Ein-Topf (One-Pot), dadurch gekennzeichnet, dass das umfasst: Reagieren von Rutin mit Anhydrid oder Acylchlorid, Kochen in einem Topf unter der Einwirkung von Säure oder Alkali, und dann direktes Herstellen von Quercetinester durch Ultraschall bei einer Leistung von 300 W für 50 min; die allgemeine Strukturformel des Quercetinesters ist wie folgt: wobei die R-Substituenten gleich oder verschieden von den folgenden Substituenten sein kônnen: Methyl, Ethyl, Propyl, Butyl, Isopropyl, Isobutyl, tert-Butyl, Phenyl, Benzyl, o-Methylphenyl, m-Methylphenyl, p-Methylphenyl, o-Ethylphenyl, m-Ethylphenyl, p-Ethylphenyl, o-Nitrophenyl, m-Hydroxyphenyl, p-Chlorphenyl, p-Bromphenyl, 2,3-Dichlorphenyl, 3,5-Dichlorphenyl.
2. Das Verfahren zur Synthese von Quercetinester durch Ein-Topf nach Anspruch 1, wobei das Anhydrid ein aliphatisches Anhydrid oder ein aromatisches Anhydrid ist.
3. Das Verfahren zur Synthese von Quercetinester durch Ein-Topf nach Anspruch 1, wobei das aliphatische Anhydrid Essigsäureanhydrid, Propionsäureanhydrid, Buttersäureanhydrid, Bernsteinsäureanhydrid oder Maleinsäureanhydrid ist, und das aromatische Anhydrid Benzoesäureanhydrid, Phenylessigsäureanhydrid, o-Toluylsäureanhydrid, p-Toluylsäureanhydrid, o-Chlorbenzoesaureanhydrid oder p-Chlorbenzoesäureanhydrid ist.
4. Das Verfahren zur Synthese von Quercetinester durch Ein-Topf nach Anspruch U503660 wobei das Acylchlorid Acetylchlorid, Propionylchlorid, Butyrylchlorid, Benzoylchlorid, Phenylacetylchlorid, o-Methylbenzoylchlorid, m-Methylbenzoylchlorid, p-Methylbenzoylchlorid oder o-Chlorbenzoylchlorid ist.
5. Das Verfahren zur Synthese von Quercetinester durch Ein-Topf nach Anspruch 1, wobei das Beschickungsverhältnis ist: Rutin: Anhydrid oder Acylchlorid: Säure oder Alkali = 1mol: 1-10ml: 0,05-1ml.
6. Das Verfahren zur Synthese von Quercetinester durch Ein-Topf nach Anspruch 1, wobei die Saure Schwefelsäure und Salzsäure ist und die Base Anilin, Piperidin oder Pyridin ist.
7. Das Verfahren zur Synthese von Quercetinester durch Ein-Topf nach Anspruch 1, wobei die Reaktionstemperatur auf 25-98°C geregelt wird und die Reaktion unter Rühren durchgeführt wird.
8. Quercetinester, synthetisiert durch Ein-Topf nach einem der Ansprüche 1 bis 7, wobeV503660 eine Strukturformel des Quercetinesters wie folgt gezeigt ist: 2) C CH,CH, 9 C CH H2CH2C CH a O7 | C CHoCH, Cala CH J | C CH C CH,CH, C CH H,CH,C C Cara C C CH CH, CO C CH CH2m H, CCH CH I | O C OH CH m H2CC‚H CH @ | C CH CH m C CH CH, C C,H CH,m H,CCH C m H,CC,H C 7) C CH CH2p © C CoH2(CH2(2 HH P pHaCCH CH S | C CH CHpp PHHHC(CH2 CH J | C CHACHA2HHP C CH CHap C CH(CH (2 HHP pH CCH C PH HH,C(,CH, C C CHCH:CHz p @ C CH2C2H2 p HCH,CCH CH @ | SE G Gr CH2CH2 p CHC CH J | C CH2C:H2 C CH CH,CH, p © CHC p HCH,CCH C CofC C C CHC 7) C CHL op CCH CH CCH CH J | I C GHC ses © | C CHCp C GHC C CHCp CCH C pCCH C C CC(C( HHH OÙ C C:C:(C(0HHH HHHC(CC CC C) | J G SG! HAH HH H(C(2C2C2 CC 0) | C CCC HHH C CC(C( HHH C C2C2(C(2HHH HHHC(CC C HH H(C(2C2C2 C
9. Anwendung von Quercetinester nach Anspruch 8 in antineoplastischen Arzneimitteln.
LU503660A 2023-03-15 2023-03-15 Method for synthesizing quercetin ester by one-pot, products and application thereof LU503660B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
LU503660A LU503660B1 (fr) 2023-03-15 2023-03-15 Method for synthesizing quercetin ester by one-pot, products and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
LU503660A LU503660B1 (fr) 2023-03-15 2023-03-15 Method for synthesizing quercetin ester by one-pot, products and application thereof

Publications (1)

Publication Number Publication Date
LU503660B1 true LU503660B1 (fr) 2023-09-15

Family

ID=88068155

Family Applications (1)

Application Number Title Priority Date Filing Date
LU503660A LU503660B1 (fr) 2023-03-15 2023-03-15 Method for synthesizing quercetin ester by one-pot, products and application thereof

Country Status (1)

Country Link
LU (1) LU503660B1 (fr)

Similar Documents

Publication Publication Date Title
EP1721903A1 (fr) Compositions et méthodes thérapeutiques mettant en jeu des isoflavones et des analogues d'isoflavones
Shimada et al. Chloroisosulochrin, chloroisosulochrin dehydrate, and pestheic acid, plant growth regulators, produced by Pestalotiopsis theae
CN106946972B (zh) 一种具有抗肿瘤活性的熊果酸衍生物及其制备方法
Maria Zbancioc et al. Synthesis and in vitro analysis of novel dihydroxyacetophenone derivatives with antimicrobial and antitumor activities
CN110028546B (zh) 具有调控凝血因子viii水平发挥抗肿瘤作用的环戊烷并多氢菲骨架化合物及其用途
LU503660B1 (fr) Method for synthesizing quercetin ester by one-pot, products and application thereof
CN101402573B (zh) 双羟基-2-酰基苯乙酸酯及其制备方法与应用
JP2012528801A (ja) グリチルレチン酸エステル誘導体の合成方法及びデオキシグリチルレチン酸エステル化合物
CN109096357B (zh) 含硫醚及胆甾醇酯的萘酰亚胺类衍生物合成和应用
Benedeković et al. Design, synthesis and cytotoxic activity of new 6-O-aroyl (−)-cleistenolide derivatives
CN106699717A (zh) A环三甲氧基黄酮取代水杨酸酯类化合物及其抗肿瘤作用
CN107698648B (zh) 含胆甾醇的萘酰亚胺类衍生物及其合成和应用
CN109485688B (zh) 三萜衍生物及其药物组合物和应用
AU2016214849B2 (en) Compound, and separation method, synthesis method and use thereof
US4061773A (en) Glycyrrhetinic acid derivatives
CN109320488B (zh) 一种3-羟基黄酮及其衍生物的水相一锅合成方法
CN110143927B (zh) 一种苯并咪唑查尔酮类衍生物及其制备方法和应用
CN109678832A (zh) 一锅煮法由芦丁合成槲皮素酯的方法及其产物和应用
Anastasiou et al. On the formation of homo‐azasteroidal esters of N, N‐bis (2‐chloroethyl) aminobenzoic acid isomers and their antitumor activity
CN1850828A (zh) 一种鬼臼毒素的衍生物及其制备方法
Jin et al. Esters of chlorambucil with 2-substituted 1, 4-dihydroxy-9, 10-anthraquinones as multifunctional anticancer agents
CN115785189B (zh) 一种5α,8α-过氧化甾醇-17-苯基噻唑衍生物及其合成方法和应用
CN110963894B (zh) 穿心莲内酯化合物及其制备方法和用途
EP3733656B1 (fr) Procédé de synthèse d'un acide lobarique et d'analogues de celui-ci
CN117820409A (zh) 一种齐墩果酸类衍生物及其制备方法和在抗肿瘤中的应用

Legal Events

Date Code Title Description
FG Patent granted

Effective date: 20230915