Mangiferin single-site derivative and preparation method and application thereof

A technology of mangiferin and derivatives, applied in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., can solve the problems of little difference in hydroxyl activity, difficulty in obtaining high-purity samples, and high cost

Active Publication Date: 2015-04-29
PEKING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is not only cumbersome to operate, but also has low efficiency and high cost, and it is difficult to obtain high-purity samples.
[0011] For the synthesis of new mangiferin, whether it is based on enzyme-catalyzed biosynthesis or chemical synthesis based on small molecule fragments, there is no relevant literature report.
At the same time, since mangiferin itself has a multi-hydroxyl skeleton structure, and the activity of each hydroxyl group is not much different, it is difficult to carry out differential modification. Therefore, the current derivatization modification of mangiferin is mostly limited to the equivalent modification of 3, 6, and 7 positions, including alkyl Etherification, aryl etherification, acylation, etc. [Liao Hongli et al., Structural modification of mangiferin, West China Pharmaceutical Journal, 2008, 4:385-387; Wu Qiuye, Mangiferin compounds and their preparation methods and their application in the field of medicine. Patent: 200610117200.0; Li Xuejian, Chemical Synthesis and Pharmacological Activity of Esterified Derivatives of Mangiferin. Doctoral Dissertation of Guangxi Medical University. 2012]

Method used

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  • Mangiferin single-site derivative and preparation method and application thereof
  • Mangiferin single-site derivative and preparation method and application thereof
  • Mangiferin single-site derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0192] Example 1: 2-C-(2,3,4,6-O-tetraacetyl-β-D-glucosyl)-1-hydroxyl-3,6,7-triacetoxyxanthone synthesis

[0193] Take 5g (11.84mmol) of mangiferin and 8.16g (99.46mmol, 8.4eq) of sodium acetate and add it to 20ml of acetic acid, heat it to 120°C while stirring, add dropwise 10ml of acetic anhydride (105.79mmol, 8.9eq) to it, and reflux the reaction After 3h, 2ml of acetic anhydride (21.16mmol, 1.8eq) was added, and the reaction was continued for 0.5h. After the reaction, the reaction solution was poured into 200ml of ice water, stirred to separate out the solid, suction filtered, the filter cake was dissolved in dichloromethane, washed 3 times with saturated aqueous sodium bicarbonate solution, washed 3 times with water, washed 3 times with saturated aqueous sodium chloride solution. Dry over sodium sulfate, concentrate, and suck to dryness to obtain 7.94 g of a yellow solid, with a yield of 93.6%. Melting point 123.9-124.8°C, [α] D =-12.0° (c 1.00, CHCl 3 ).

[0194] 1...

Embodiment 2

[0195] Example 2: 2-C-(2,3,4,6-O-tetraacetyl-β-D-glucosyl)-1,3,6-tribenzyloxy-7-acetoxyxanthene Ketone synthesis

[0196]Take 5g (6.98mmol ) was dissolved in 100ml of acetone, potassium carbonate 11.57g (83.73mmol, 12eq), potassium iodide 1.16g (6.98mmol, 1eq), benzyl bromide 4.97ml (41.86mmol, 6eq) were added thereto, stirred at room temperature for 0.5h and then moved to Reflux reaction at 60°C for 13h. After the reaction was completed, the reaction solution was filtered, and the filtrate was concentrated. Petroleum ether: ethyl acetate = 1:1 column chromatography separation to obtain 5.35 g of white solid with a yield of 84.9%. Melting point 218.0-219.6°C, [α] D =-67.4° (c 0.95, CHCl 3 ).

[0197] 1 H NMR (400MHz, CDCl 3 )δ7.93(s,1H),7.68–7.52(m,4H),7.50–7.07(m,11H),6.83(s,1H),6.74(s,1H),6.09(t,J=9.7Hz ,1H),5.34–4.80(m,9H),4.20(dd,J=12.4,4.0Hz,1H),3.96(d,J=11.2Hz,1H),3.39(dt,1H),2.26(s, 3H), 2.01(s,3H), 1.96(s,3H), 1.89(s,3H), 1.77(s,3H). 13 CNMR (100MHz, CDCl 3...

Embodiment 3

[0198] Example 3: 2-C-(2,3,4,6-O-tetraacetyl-β-D-glucosyl)-7-hydroxyl-1,3,6-tribenzyloxyxanthone synthesis

[0199] Take 2-C-(2,3,4,6-O-tetraacetyl-β-D-glucosyl)-1,3,6-tribenzyloxy-7-acetoxyxanthone 5g ( 5.54mmol) was added to 100ml mixed solvent (methanol: acetone: water = 4:2:1), 3.41g (44.30mmol, 8eq) of ammonium acetate was added thereto, and refluxed at 60°C for 12h. After the reaction was completed, the reaction solution was concentrated and evaporated to dryness. The residue was dissolved in dichloromethane, washed three times with water and three times with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. Dichloromethane: acetone = 30:1 column chromatography to obtain 4.02 g of yellow solid with a yield of 84.4%. Melting point 111.7-112.9°C, [α] D =-60.0° (c 1.00, CHCl 3 ).

[0200] 1 H NMR (400MHz, CDCl 3 )δ7.68–7.55(m,5H),7.49–7.22(m,11H),6.72(s,1H),6.67(s,1H),6.43(s,1H),6.08(t,J=9.7Hz ,1H),5.44–4.78(m,9H),4.1...

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Abstract

The invention discloses a mangiferin single-site derivative, which is as shown in a formula I-I, wherein definition of R6 is specified in the specification. In addition, the invention further discloses a preparation method of the derivative. The derivative is capable of inhibiting diabete-related enzymes such as PTP1B and alpha-glycosidase, so as to play a role of reducing blood sugar; meanwhile, a mangiferin compound has wide physiological activity; and side effects on a human body caused by traditional hypoglycemic drugs can be avoided.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, and more specifically relates to a novel single-site derivative of mangiferin, its preparation method and its application in the preparation of diabetes drugs. Background technique [0002] Mangiferin (Mangiferin, 2-C-β-D-glucosyl-1,3,6,7-tetrahydroxyxanthone) is a natural polyphenolic carbon glycoside compound with a xanthone structure , mainly found in the fruits, leaves, and bark of Mango (Mangiferin indica L), rhizomes and aerial parts of Liliaceae Anemarrhena (Anemarrhena asphodeloides Bge.), and Belamcanda chinensis (L.) DC.) in flowers, leaves and other plants [Li Haowen, Deng Jiagang, Deng Jing. Research progress of mangiferin abroad. Journal of Guangxi University of Traditional Chinese Medicine, 2003, 6(4): 62-66]. Neomangiferin (Neomangiferin, 2-C-β-D-glucosyl-7-O-β-D-glucosyl-1,3,6-trihydroxyxanthone) is the 7-O-glucose of mangiferin Glycoside derivatives, mostly present in the rhi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D407/04C07H17/04C07H1/00A61K31/352A61K31/5377A61K31/7048A61P3/10
CPCY02P20/55C07D407/04C07H17/04
Inventor 李中军梁丹琳魏雄王青孟祥豹李树春陈世忠
Owner PEKING UNIV
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