Synthesis method of isolicoflavonol

A technology of isolicorice flavonol and synthesis method, applied in organic chemistry, bulk chemical production, etc., can solve the problems of high cost, low output, long preparation process, etc., and achieve low production cost, high product yield, and simple raw materials Effect

Pending Publication Date: 2020-12-08
SUZHOU HIGHFINE BIOTECH
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Problems solved by technology

At present, isolicorice flavonol mainly relies on extraction from natural plants, which has the bottleneck of long preparation process, low yield and high cost

Method used

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  • Synthesis method of isolicoflavonol
  • Synthesis method of isolicoflavonol
  • Synthesis method of isolicoflavonol

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preparation example Construction

[0112] As shown in the above formula (II), the synthetic method according to the present invention specifically includes:

[0113] Step S1, the 2,4-O-protecting group R 1 -6-hydroxyl-acetophenone (compound shown in structural formula 3) and 4-O-protecting group R 2 -benzaldehyde (compound shown in structural formula 5) is condensed to generate 2', 4'-O-protecting group R 1 -6'-Hydroxy-4-O-protecting group R 2 - Chalcone (compound represented by structural formula 6).

[0114] Wherein, the protecting group R 1 , R 2 independently selected from -CH 3 ,-CH 2 OCH 3 , the group formed by benzyl, allyl, acetyl, isopentenyl, 1,1-dimethyl-propynyl. That is, the protecting group R 1 , R 2 They can be the same or different, and there is no interdependence between them, and they can be arbitrarily selected from the above-mentioned groups.

[0115] Specifically, the 2,4-O-protecting group R 1 -6-hydroxyl-acetophenone can be prepared through the following steps:

[0116] In st...

example 1

[0141] Example 1 Synthesis of 2,4,6-trihydroxyacetophenone (compound shown in structural formula 2)

[0142] Under cooling in an ice-salt bath, add phloroglucinol 1 (10.0 g, 0.080 mol), anhydrous acetonitrile (9.7 ml, 0.185 mol), anhydrous ZnCl 2 (2.81g, 0.021mol) and 42ml of anhydrous diethyl ether, under stirring, dry HCl gas was passed through for 6h, and a large amount of light yellow solid was formed.

[0143] Stop the reaction, put the reaction solution in the refrigerator and let it stand for 3d. Access to N 2The residual HCl gas was removed, filtered, and the filter cake was washed twice with 20 ml of anhydrous ether. The filter cake and 2.5 g of activated carbon were added to 500 ml of deionized water, refluxed for 2.5 h, filtered while hot, and recrystallized to obtain pale yellow needle crystals. The solid was vacuum-dried at 120°C for 4 h to obtain 10.76 g of orange-red crystals (yield: 80.7%) .

[0144] m.p.215.4-217.7℃.IRνmax(KBr / cm-1):3291(OH),1626(C=O),1590...

example 2

[0149] Example 2 Synthesis of 2,4-dimethoxy-6-hydroxyl-acetophenone (one of the compounds shown in structural formula 3, denoted as 3a)

[0150] Compound 2 (10.0g, 0.059mol) was dissolved in 100ml of acetone, anhydrous potassium carbonate (24.58g, 0.178mol) was added, under stirring, dimethyl sulfate (13ml, 0.137mol) was added dropwise, heated to reflux for 1.5h, Cool to room temperature, remove solid potassium carbonate by filtration to obtain an orange-yellow acetone solution, and rotary evaporate to obtain 11.24 g of a yellow crude product. The crude product is recrystallized with 50 ml of ethanol-water to obtain a white solid, and then vacuum-dried at 45 ° C for 12 hours to obtain an orange-red solid 9.25 g (85.7% yield).

[0151] m.p.74.5-77.0°C, 1 H NMR (400MHz, DMSO) δ13.80(s, 1H), 6.09(d, J=2.3Hz, 1H), 6.06(d, J=2.3Hz, 1H), 3.85(s, 3H), 3.80(s ,3H),2.53(s,3H).

[0152] 13 C NMR (101MHz, DMSO) δ202.76, 166.23, 165.94, 162.77, 105.44, 93.61, 90.76, 55.98, 55.65, 32.6...

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Abstract

The invention provides a synthesis method of isolicoflavonol, which comprises the following steps: carrying out condensation reaction on 2,4-O-R1(protective group, the same below)-6-hydroxyacetophenone and 4-O-R2(protective group, the same below)-benzaldehyde to generate 2',4'-O-R1-6'-hydroxy-4-O-R2-chalcone; oxidizing the chalcone to generate flavonol; carrying out selective protection on 3-OH ofthe flavonol to obtain 3,5,7-O-R1-4'-O-R2-flavonol; removing the protecting group R2 from the 3,5,7-O-R1-4'-O-R2-flavonol to obtain 3,5,7-O-R1-4'-hydroxyflavonol; carrying out 1,1-dimethylpropargyl reaction on the 4,4'-OH site to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonol; carrying out partial hydrogenation on the alkynyl of the 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonolunder the action of a catalyst to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol and carrying out Claisen rearrangement on the 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol to obtain 3,5,7-O-R1-isolicoflavonol, and removing the protecting group R1 from the 3,5,7-O-R1-isolicoflavonol to obtain the isolicoflavonol.

Description

technical field [0001] The invention relates to the field of preparation of pharmaceutical intermediates, in particular to a method for synthesizing isolicorice flavonol. Background technique [0002] Licorice is one of the most widely used traditional Chinese medicines. For a long time, Chinese medicine has applied it to the treatment of tuberculosis, hepatitis and bronchitis, and the effect is remarkable. Licorice has many important pharmacological activities, such as: antibacterial, antitumor, anti-inflammatory, antiviral, detoxification, antiplatelet aggregation, inhibition of histamine-induced ulcers, regulation of immune function, etc. (Fu Y, Chen J, Zheng Y F, et al. al.Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice[J].Food Chemistry,2013,141(2):1063-1071.). [0003] At present, more than 300 flavonoids with certain biological activities have been isolated and identified from licorice, including flavones, dihydroflavones, isof...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/30
CPCC07D311/30Y02P20/55
Inventor 陆雪根顾寿胜顾耿峰
Owner SUZHOU HIGHFINE BIOTECH
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