Diphyllin ether derivative and preparation method and application thereof

A technology of lotus leaf ether and derivatives, which is applied in the fields of medicinal chemistry and pharmacology, can solve the problems of poor metabolic stability of glycosidic bonds, hydrolysis inactivation of glycosidase, complicated chemical synthesis, etc., and achieves the effect of strong tumor cell proliferation inhibition activity.

Active Publication Date: 2020-06-19
南通大学技术转移中心有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the chemical synthesis of glycoside compounds is relatively complicated, and the metabolic stability of glycosidic bonds is not good, and they are easily hydrolyzed and inactivated by endogenous glycosidases.

Method used

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  • Diphyllin ether derivative and preparation method and application thereof
  • Diphyllin ether derivative and preparation method and application thereof
  • Diphyllin ether derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Dissolve 190mg (0.5mmol) of kaempferol in 6mL of DMF, add 343mg (2.5mmol) of epibromohydrin and 414mg (3.0mmol) of anhydrous potassium carbonate, and react at 60°C for 2h. TLC detected the end of the reaction, added 50mL of ethyl acetate to dilute, then washed with water and saturated brine successively, MgSO 4 Drying, drying under reduced pressure, column chromatography (prtroleum ether:EtOAc=1:1, R f =0.3) 174 mg of light yellow solid was obtained, the yield was 80%. Dissolve the light yellow solid in 20 mL of MeOH, add 88 mg (1.2 mmol) of n-butylamine, react at 65 ° C for 3 h, TLC monitors the end of the reaction, MgSO 4 Drying, drying under reduced pressure, column chromatography (DCM:MeOH=20:1, R f = 0.3) 124 mg of white powder 4-O-(3'-butylamino-2'-hydroxypropyl)-baciferin (2a) was obtained with a yield of 61%.

[0045] For NMR detection of 4-O-(3'-butylamino-2'-hydroxypropyl)-kaempferol (2a), see figure 1 and figure 2 , resulting in: 1 H NMR (400MHz, CDCl ...

Embodiment 2

[0047] According to the method of Example 1 above, 88mg (1.2mmol) of n-butylamine was replaced by 128mg (1.2mmol) of benzylamine to prepare 4-O-(3'-benzylamino-2'-hydroxypropyl) -Nuciferin (2b), the physicochemical data of this compound are:

[0048] 2b: 1 H NMR (400MHz, CDCl 3 )δ: 7.64(s,1H,ArH),7.39-7.30(m,5H,ArH),7.06(s,1H,ArH),6.95(d,J=7.9Hz,1H,ArH),6.85-6.75( m,2H,ArH),6.06(dd,J=19.8,1.4Hz,2H,OCH 2 O),5.44(s,2H,ArCH 2 O), 4.24–4.06 (m, 3H, CH 2 ,CH),4.01(s,3H,OCH 3 ), 3.87 (d, J=5.3Hz, 2H, CH 2 ),3.80(s,3H,OCH 3 ),3.04-2.72(m,2H,CH 2 ). 13 C NMR (100MHz, CDCl 3 )δ: 169.7, 151.7, 150.3, 147.5, 146.7, 139.7, 135.1, 130.7, 128.6, 128.4, 128.1, 127.4, 126.9, 126.7, 123.6, 119.2, 110.8, 108.2, 1066.2, 1031.2, 8.5, 10 ,56.1,55.8,53.8,50.9.HRMS(ESI):m / z calcd for C 31 h 30 NO 8 :544.1964; found: 544.1961[M+H] + .

Embodiment 3

[0050] According to the method of Example 1 above, 88 mg (1.2 mmol) of n-butylamine was replaced with 112 mg (1.2 mmol) of aniline to prepare 4-O-(3'-anilino-2'-hydroxypropyl)-shank Nuciferin (2c), the physicochemical data of this compound are:

[0051] 2c: 1 H NMR (400MHz, CDCl 3 )δ: 7.60 (s, 1H, ArH), 7.25-7.13 (m, 2H, ArH), 7.04 (s, 1H, ArH), 6.91 (d, J=7.9Hz, 1H, ArH), 6.83-6.62 ( m,5H,ArH),6.17-5.88(m,2H,OCH 2 O),5.41(s,2H,ArCH 2 O), 4.35(td, J=6.8, 3.1Hz, 1H, CH), 3.99(s, 3H, OCH 3 ),4.29-4.20(m,2H,CH 2 ),3.79(s,3H,OCH 3 ),3.58-3.31(m,2H,NCH 2 ). 13 C NMR (100MHz, CDCl 3 )δ: 169.9, 151.8, 150.3, 148.0, 147.5, 146.5, 135.2, 130.7, 129.4, 128.3, 126.5, 123.6, 119.1, 118.4, 113.3, 110.7, 108.2, 106.3, 1561.3, 100.4, 9.4 ,55.9,46.7.HRMS(ESI):m / zcalcd for C 30 h 28 NO 8 :530.1807; found: 530.1804[M+H] + .

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Abstract

The invention belongs to the technical field of medicinal chemistry and pharmacology, and relates to a diphyllin ether derivative and a preparation method and application thereof. The chemical structural formula of the diphyllin ether derivative is shown as a formula (I), the diphyllin ether derivative is prepared by reacting diphyllin with anhydrous potassium carbonate and epoxy bromopropane in N, N '-dimethylformamide to obtain 4-O-epoxypropyl diphyllin, and then reacting the 4-O-epoxypropyl diphyllin with a corresponding amine compound or a nitrogen-containing heterocyclic compound in methanol. The diphyllin ether derivative has high activity of inhibiting tumor cell growth and can be expected to be used as an antitumor drug.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and pharmacology, and in particular relates to a basilicin ether derivative and a preparation method and application thereof. Background technique [0002] With the advancement of medicine, common infectious diseases are gradually being controlled, and malignant tumor-cancer has become one of the main diseases that are common and seriously threaten human life and quality of life. Plant-derived antitumor drugs play an important role in clinical treatment. In recent years, studies have found that the xyloside Cleistanthin-A and the quinoloside Patentiflorin A of the natural lignan kaempferin have strong anti-tumor activity. However, the chemical synthesis of glycoside compounds is relatively complicated, and the metabolic stability of glycosidic bonds is not good, and they are easily hydrolyzed and inactivated by endogenous glycosidases. [0003] Contents of the invention [0004]...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D407/04C07D405/14A61K31/365A61K31/4178A61K31/4525A61K31/5377A61P35/00
CPCC07D407/04C07D405/14A61P35/00
Inventor 赵育包小峰朱力
Owner 南通大学技术转移中心有限公司
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