Copper chloride complex of 1-(2-pyridine)-9-(3-phenylpropyl)-beta-carboline and synthetic method and application thereof

Abstract

The invention discloses copper chloride complex of 1-(2-pyridine)-9-(3-phenylpropyl)-beta-carboline and a synthetic method and application thereof. The complex has a structural formula shown as in formula (I) below, and the synthetic method of the complex comprises: dissolving a compound shown as in formula (II) and copper chloride in a polar solvent, and carrying out coordination reaction to obtain the complex, wherein the polar solvent is a composition of one or both of methanol and ethanol and one or more than two of water, acetone, chloroform, dichloromethane and N,N-dimethylformamide. The complex described herein exhibits higher antitumor activity than the ligand and cis-platinum, has good medicinal value and is expectedly applicable to the preparation of various antitumor drugs. The structures shown as in the formulas (I) and (II) are shown in the description.

Description

technical field

[0001] The invention relates to the technical field of medicine, in particular to a copper chloride complex of 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline and its synthesis method and application. Background technique

[0002] β-carbolines are a class of alkaloids widely distributed in nature, and they mainly exist in a variety of terrestrial plants and marine organisms. In terms of chemical structure, β-carboline alkaloids belong to indole alkaloids, which are tricyclic ring systems composed of indolopyridines. Atoms exist in different hybridization states, the nitrogen atom at position 9 is sp 3 Hybridization, rich π-electron system, 2-position nitrogen atom is sp 2 Hybridization is a π-electron-deficient system. The two nitrogen atoms are closely related to the chemical properties and biological activities of these compounds. Such compounds have a wide range of biological and pharmacological activities, including: sedative, anxiolytic, hypnotic, anti...

Examples

Embodiment 1

[0044] Embodiment 1: The compound shown in formula (II) is the synthesis of 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline (L)

[0045] 1) Add 1.6g (10mmol) tryptamine, 1.1g (10mmol) pyridine-2-carbaldehyde and 50ml toluene into a 150ml round bottom flask, add a water separator and a condenser tube to form a component water reflux device, heat and reflux for 4 hours, wait After the reaction, the solvent was evaporated to dryness, and the residue was recrystallized with 100ml of n-hexane to obtain compound 1 (2.3g, yield 92%);

[0046] 2) Add 2.5g (10mmol) compound 1, 2.5g palladium carbon (10%Pd / C) and 100ml p-xylene to a 250ml round bottom flask, heat to reflux, and use thin layer chromatography to track and detect until the end of the reaction, and let stand Suction filtration and the filtrate was evaporated to dryness, and the resulting residue was purified by silica gel column chromatography (V 石油醚 :V 二氯甲烷 =1:1), to obtain compound 2 (2.1g, yield 86%);

[0047] 3) Add 0....

Embodiment 2

[0055] Embodiment 2: the synthesis of ligand L

[0056] Repeat Example 1, the difference is:

[0057] In step 2), with Mn(Ac) 3 Instead of palladium carbon, glacial acetic acid instead of p-xylene, control Mn(Ac) 3 The amount of compound 1 added was twice that of compound 1, and the reaction was carried out at 70°C. TLC was tracked and detected until the end of the reaction, and then the pH of the system was adjusted to 7 with ammonia water, extracted three times with ethyl acetate, and the organic phases were combined. , evaporate the solvent to dryness, and the resulting residue is applied to a silica gel column (chromatographic purification (V 石油醚 :V 二氯甲烷 =1:1), compound 2 was obtained.

[0058] The product obtained in this example was analyzed by H NMR, C NMR and high-resolution mass spectrometry, and it was determined to be the target product 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline.

Embodiment 3

[0059] Embodiment 3: the synthesis of ligand L

[0060] Repeat Example 2, the difference is:

[0061] In step 2), with Pb(Ac) 4 instead of Mn(Ac) 3 , to control Pb(Ac) 4 The amount of added is 5 times the amount of compound 1, and the reaction is carried out at 60°C.

[0062] The product obtained in this example was analyzed by H NMR, C NMR and high-resolution mass spectrometry, and it was determined to be the target product 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline.

technical field

[0001] The invention relates to the technical field of medicine, in particular to a copper chloride complex of 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline and its synthesis method and application. Background technique

[0002] β-carbolines are a class of alkaloids widely distributed in nature, and they mainly exist in a variety of terrestrial plants and marine organisms. In terms of chemical structure, β-carboline alkaloids belong to indole alkaloids, which are tricyclic ring systems composed of indolopyridines. Atoms exist in different hybridization states, the nitrogen atom at position 9 is sp 3 Hybridization, rich π-electron system, 2-position nitrogen atom is sp 2 Hybridization is a π-electron-deficient system. The two nitrogen atoms are closely related to the chemical properties and biological activities of these compounds. Such compounds have a wide range of biological and pharmacological activities, including: sedative, anxiolytic, hypnotic, anti...

Examples

Embodiment 1

[0044] Embodiment 1: The compound shown in formula (II) is the synthesis of 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline (L)

[0045] 1) Add 1.6g (10mmol) tryptamine, 1.1g (10mmol) pyridine-2-carbaldehyde and 50ml toluene into a 150ml round bottom flask, add a water separator and a condenser tube to form a component water reflux device, heat and reflux for 4 hours, wait After the reaction, the solvent was evaporated to dryness, and the residue was recrystallized with 100ml of n-hexane to obtain compound 1 (2.3g, yield 92%);

[0046] 2) Add 2.5g (10mmol) compound 1, 2.5g palladium carbon (10%Pd / C) and 100ml p-xylene to a 250ml round bottom flask, heat to reflux, and use thin layer chromatography to track and detect until the end of the reaction, and let stand Suction filtration and the filtrate was evaporated to dryness, and the resulting residue was purified by silica gel column chromatography (V 石油醚 :V 二氯甲烷 =1:1), to obtain compound 2 (2.1g, yield 86%);

[0047] 3) Add 0....

Embodiment 2

[0055] Embodiment 2: the synthesis of ligand L

[0056] Repeat Example 1, the difference is:

[0057] In step 2), with Mn(Ac) 3 Instead of palladium carbon, glacial acetic acid instead of p-xylene, control Mn(Ac) 3 The amount of compound 1 added was twice that of compound 1, and the reaction was carried out at 70°C. TLC was tracked and detected until the end of the reaction, and then the pH of the system was adjusted to 7 with ammonia water, extracted three times with ethyl acetate, and the organic phases were combined. , evaporate the solvent to dryness, and the resulting residue is applied to a silica gel column (chromatographic purification (V 石油醚 :V 二氯甲烷 =1:1), compound 2 was obtained.

[0058] The product obtained in this example was analyzed by H NMR, C NMR and high-resolution mass spectrometry, and it was determined to be the target product 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline.

Embodiment 3

[0059] Embodiment 3: the synthesis of ligand L

[0060] Repeat Example 2, the difference is:

[0061] In step 2), with Pb(Ac) 4 instead of Mn(Ac) 3 , to control Pb(Ac) 4 The amount of added is 5 times the amount of compound 1, and the reaction is carried out at 60°C.

[0062] The product obtained in this example was analyzed by H NMR, C NMR and high-resolution mass spectrometry, and it was determined to be the target product 1-(2-pyridine)-9-(3-phenylpropyl)-β-carboline.

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