Gambogic acid cyclized analog, preparation method and application thereof

An analog, the technology of gambogic acid, which is applied to the cyclized analog of gambogic acid and the fields of its preparation and application, can solve the problems of low anti-cancer activity, high toxicity, apoptosis and the like of gambogic acid

Active Publication Date: 2009-12-30
LIAONING LIFENG SCI & TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, there is no report on the structure modification of C-4, C-6, C-8 or and C-10 in the literature, patents or patent applications worldwide to form gambogic acid ring closure analogues, nor through the introduction of ring In order to solve the problem of low anticancer activity and high toxicity of gambogic acid
[0008] Another

Method used

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  • Gambogic acid cyclized analog, preparation method and application thereof
  • Gambogic acid cyclized analog, preparation method and application thereof
  • Gambogic acid cyclized analog, preparation method and application thereof

Examples

Experimental program
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preparation example Construction

[0067] 1. Preparation of gambogic acid (see Xu Lifeng Chinese patent application 200710157223.9)

[0068] 2. Chemical synthesis and preparation

[0069] Synthesis and preparation of esters, anhydrides and amides at the 30th position of the gambogic acid ring-closure analog structure: modify the structure at the 30th position of the gambogic acid structure, modify the carboxyl group into esters and amide analogues, and use gambogic acid as the raw material , using one of the following reagents (tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, n-hexane, toluene , quinoline, etc.) as the solvent, the reaction temperature is -78 ° C to 90 ° C, using one or more catalysts, which can catalyze the formation of C-O bonds, C-S bonds, C-N bonds, C-P bonds, gambogic acid derivatives Compounds and analogs react with alcohols, thiols, acids, amines and phosphorus-containing compounds with or without substituents to produce esters, ...

Embodiment 1

[0083] Preparation of Example 1 (see Table 1 Compound 1, the same below)

[0084] Compound 1.1: In a 250ml round bottom flask, add gambogic acid 12.56g (20mmol) successively, catalytic amount 4-dimethylaminopyridine (DMAP), tetrahydrofuran (THF) 80ml, N, N dimethylformamide (DMF) 20ml, the reaction system was placed on a heat collecting type constant temperature heating magnetic stirrer, after stirring for 30 minutes, add ethanolamine 1.22g (20mmol), stir at room temperature for 8 hours, add glacial acetic acid 1.3ml, continue stirring for 8 hours, the reaction solution 40 Concentrate under reduced pressure at ℃ to distill THF, extract the aqueous phase with ethyl acetate, add anhydrous magnesium sulfate to dry, and the filtrate is recovered under reduced pressure to obtain a light yellow solid, which is separated by silica gel column chromatography to obtain compound 1.1 (see Table 1 Compound 1.1, below same). IR (KBr, cm -1 ): 3422, 2965, 2925, 2855, 1738, 1711, 1633, 1594...

Embodiment 2

[0087] Preparation of Example 2

[0088]Compound 2.1: In a 250ml round bottom flask, add 12.84g (20mmol) of methyl gambogic acid, 3.50g (24mmol) of 1,3-indanedione, 3.85g (50mmol) of ammonium acetate, and dry DMF 60ml, and react The system was placed on a collector-type constant temperature heating magnetic stirrer, the reaction system was sealed, and the reaction was stopped after stirring at 35° for 24 hours under the protection of dry nitrogen. The reaction solution was extracted by adding 150ml of ethyl acetate and 150ml of water respectively. After the ethyl acetate phase was separated, the ethyl acetate phase was extracted with 100, 100, and 50ml of water respectively. After the DMF was extracted, it was dried with anhydrous magnesium sulfate for 8 hours, the anhydrous magnesium sulfate was removed by filtration, the filtrate was mixed with 160-200 mesh silica gel, and 4.2 g of compound 2.1 was obtained by column chromatography with a yield of 27.27%. IR (KBr, cm -1 ):...

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Abstract

The invention discloses a gambogic acid cyclized analog, a preparation method and application thereof. The semi-synthesized gambogic acid cyclized analog is obtained by the extracted and purified gambogic acid through chemical synthesis and has a structural general formula I-III as the right formula, wherein substituent groups of A ring, B ring, C ring, R1, R2, R3, R4, R5, R6, R7, R7, R8, R9, R10, R11 or/and R12 contain glycosyl group, polyhydroxy, amino acid group, acyloxy group, phosphoric acid oxygen group, sulphonic acid oxygen group, alkoxyl group, aromatic oxygen group, heterocyclic oxygen group, mercapto group, substituted mercapto group, primary amine and secondary amines groups or/and substituted primary amine and secondary amines groups, and chain hydrocarbon or and cyclic group containing oxygen, sulphur, nitrogen, carbon or/and phosphor atoms, and one or combination of the substitution groups. The gambogic acid cyclized analog has anti-tumor, antivirus, antibacterial and antifungal pharmacology activities, can be used as anti-tumor, antivirus, immune, antibacterial and antifungal medicaments, and can be applied together with the known anti-tumor, antivirus, immune, antibacterial and antifungal medicaments.

Description

field of invention [0001] The present invention relates to a new compound gambogic acid cyclization analog with anti-tumor activity and its medicinal chemistry research and preparation method. The invention also relates to the application of the compound as anti-tumor and other disease drugs. Background technique [0002] Medicinal garcinia is the resin of the Garcinia cambogia plant, also known as sea vine, jade yellow, moon yellow, wax yellow and so on. Native to India, Thailand, etc., mainly in Cambodia, Thailand and Vietnam, and cultivated in Guangdong and Hainan provinces of my country (Document 1: Wang Ming, Feng Xu, Zhao Youyi, Fu Hui, Research and Application of Chinese Medicine Garcinia Cambogia, Chinese Wild Plant Resources, 2003, 22(1), 1-3; Literature 2: Liu Wenyuan, Feng Feng, Chen Yousheng, You Qidong, Zhao Shouxun, Structural Research on Gambogic Acid-Alkali Degradation Products, China Natural Medicine, 2004, 2(2 ), 75-77). [0003] Gambogic resin contains gam...

Claims

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Application Information

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IPC IPC(8): C07H15/26C07D493/22C07D491/22C07D513/22C07F9/6561C07H17/04A61K31/7048A61K31/352A61K31/4741A61K31/706A61K31/529A61K31/496A61K31/5377A61K31/537A61K31/554A61K31/675A61K31/4196A61K31/4178A61K31/55A61P35/00A61P31/12A61P31/04A61P31/10A61P37/02
CPCC07D493/22C07F9/6561C07D491/22C07H15/26C07H17/04A61K31/4188C07D513/22A61K31/352A61P31/04A61P31/10A61P31/12A61P35/00A61P35/02A61P37/02
Inventor 徐利锋
Owner LIAONING LIFENG SCI & TECH DEV
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