Quercetin derivative and preparation method and application thereof

A technology of quercetin and derivatives, which is applied in the field of compound preparation and application, can solve problems such as unseen systematic research, achieve obvious pathological hyperplasia, excellent inhibition of NRK-49F proliferation activity, and pathological hyperplasia inhibition

Active Publication Date: 2015-04-29
南京盈博医药生物技术创新研究院有限公司
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

Quercetin directly participates in the reaction to obtain mixed products with multiple substitutions coexisting, so the select

Method used

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  • Quercetin derivative and preparation method and application thereof
  • Quercetin derivative and preparation method and application thereof
  • Quercetin derivative and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1 5

[0022] The synthesis of embodiment 1 five substituted quercetins and four substituted quercetins

[0023] Compound 2a: Dissolve quercetin 1 (500mg, 1.65mmol) in 15mL DMF, add acetic anhydride (1.25mL, 13.24mmol), triethylamine (2.76mL, 20mmol), stir the reaction system at room temperature for 3h, and detect the raw materials by TLC The reaction disappeared completely. The reaction solution was poured into ice water, a white solid was precipitated, the suspension was filtered to obtain a crude product, and the crude product was recrystallized with methanol to obtain a white compound 2a with a yield of 83%. Product characterization: 1 HNMR (300MHz, CDCl 3 ) δppm7.75–7.66 (m, 2H), 7.39–7.31 (m, 2H), 6.88 (d, J=1.9Hz, 1H), 2.43 (s, 3H), 2.34 (s, 6H), 2.34 (s , 6H). MS-ESI (m / z): [M+H] + : 513.10.

[0024] Compound 2b: Dissolve quercetin 1 (300mg, 1.00mmol) in 10mL DMF, add acetic anhydride (0.37mL, 4.00mmol), triethylamine (0.83mL, 6.00mmol), react the reaction system at roo...

Embodiment 2

[0030] The synthesis of embodiment 2 selective protection quercetin compounds

[0031] Compound 5: Quercetin 1 (302mg, 1.00mmol) was dissolved in 20mL of diphenyl ether, dichlorodiphenylmethane (300μL, 1.50mmol) was added, and the reaction system was stirred at 175°C for 0.5h, and the raw materials basically disappeared as detected by TLC . After the reaction solution was cooled to room temperature, a dark red solid was precipitated after adding 50 mL of petroleum ether, and the crude product was obtained by filtration. The crude product was subjected to column chromatography (PE:EtOAc=4:1) to obtain compound 5 with a yield of 86%. Product characterization: 1 HNMR (300MHz, DMSO-d 6 ) δppm 12.38 (s, 1H), 10.84 (s, 1H), 9.66 (s, 1H), 7.86–7.77 (m, 2H), 7.61–7.50 (m, 4H), 7.49–7.39 (m, 6H) , 7.20 (d, J=8.3Hz, 1H), 6.47 (d, J=2.0Hz, 1H), 6.19 (d, J=2.0Hz, 1H).

[0032] Compound 6: Compound 5 (932 mg, 2.00 mmol) was dissolved in 30 mL of acetone, and K 2 CO 3 (1.38g, 10.00mmo...

Embodiment 3

[0038] Synthesis of compound in the derivatization reaction of embodiment 3 intermediate 5

[0039] Compound 12a: Compound 5 (600 mg, 1.29 mmol) was dissolved in 20 mL of acetone, and K 2 CO 3 (1.4g, 10mmol), Me 2 SO 4 (0.61mL, 6.44mmol), the reaction system was stirred and reacted at 60°C for 3h, and TLC detected that the starting material disappeared completely. The reaction solution was filtered to remove inorganic salts, and the filtrate was spin-dried to obtain a crude product. The crude product was subjected to column chromatography (PE:EtOAc=1:2) to obtain compound 12a with a yield of 75%. Product characterization: 1 HNMR (300MHz, CDCl 3 ) δppm7.72-7.66 (m, 2H), 7.64–7.56 (m, 4H), 7.44–7.36 (m, 6H), 6.99 (d, J=8.3Hz, 1H), 6.47 (d, J=2.2Hz , 1H), 6.33 (d, J=2.2Hz, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.88 (s, 3H).

[0040] Compound 12b: Compound 5 (200 mg, 0.43 mmol) was dissolved in 15 mL of acetone, and K 2 CO 3 (326mg, 2.36mmol), diethyl sulfate (186μL, 2.14mmol)...

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Abstract

The invention discloses a quercetin derivative and a preparation method and application thereof. The preparation method comprises the following steps: firstly using dichlorodiphenylmethane to protect quercetin o-diphenol hydroxyl, combining a benzyl protection group to obtain the selectively protected quercetin derivative, and then independently reacting with dimethyl sulfate, diethyl sulfate, allyl bromide, paratoluensulfonyl chloride and acetic anhydride respectively to generate corresponding quercetin derivatives. All of the prepared derivative compounds have NRK-49F proliferation activity inhibition superior to that of quercetin. The quercetin derivatives 20a-1, 14a-1 and 23d-1 compositely replaced by methyl and p-tosyl have higher inhibition NRK-49F proliferation activity, and the inhibition ratio respectively reaches 86.33%, 78.04% and 75.91%. Thus, the currently obtained quercetin derivative compounds have obvious inhibition effect on kidney fibroblast NRK-49F proliferation.

Description

technical field [0001] The invention relates to the technical field of compound preparation and application, in particular to a quercetin derivative and its preparation method and application. Background technique [0002] Quercetin is a polyphenolic hydroxyflavonol compound with the following chemical structure: [0003] [0004] Its characteristic structure is that besides the basic structure of chromone, it contains five phenolic hydroxyl groups. Quercetin has a wide range of pharmacological effects and biological activities, and has mild performance, low toxicity and side effects, and has very high medicinal value. Quercetin is a strong natural antioxidant, which can expand coronary blood vessels, lower blood pressure, protect myocardial ischemia, and resist platelet aggregation. It is also an active compound for anticancer, antibacterial, antiallergic, antiviral, and analgesic. Nevertheless, quercetin's relatively weak pharmacological activity and low bioavailabili...

Claims

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Application Information

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IPC IPC(8): C07D407/04C07D311/30A61K31/36A61K31/352A61P1/16A61P13/12A61P11/00
CPCY02P20/55C07D407/04C07D311/30
Inventor 李建新
Owner 南京盈博医药生物技术创新研究院有限公司
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