Organic germanium-base quinolinate compound and its synthesis method

Abstract

The invention relates to a category of rganic germanium-base quinolinate compound and its synthesis method, which consists of selecting organic germanium acyl chlorine and 8-hydroxy quinoline as starting raw material for substitution reaction, carrying out hydrolysis reaction at normal temperature, and varying solvent to obtain water-soluble organic germanium quinoline ester compound, which has strong anti-tumor activity.

Description

technical field

[0001] The invention belongs to an organic germanium quinoline ester compound and a synthesis method thereof. Background technique

[0002] Since 1968, Japanese scholar Asai Yiyan and others have synthesized water-soluble β-carboxyethyl germanium sesquioxide-(GeCH 2 CH 2 COOH) 2 o 3 , that is, Ge-132, and since its anti-cancer, anti-virus, anti-aging and other biological effects were discovered, the synthesis of new organic germanium compounds and the research on anti-cancer activity have become an important field for people to develop high-efficiency and low-toxicity anti-cancer drugs. People have synthesized many Ge-132 derivatives, containing -GeO 3 Various types of organic germanium compounds, such as Ge-132 analogues of the group, bridge oxygen germanium ring compounds, etc., have studied their anticancer effects in many aspects. Since the 1970s, Japan, the United States, the former Soviet Union, China and other countries have successively synthesiz...

Examples

Embodiment 1

[0016] Embodiment 1: synthetic quinoline ester ethyl germanium sesquioxide

[0017]

[0018] First, trichlorogermanyl propionyl chloride was synthesized according to the literature method.

[0019] Under cooling in an ice bath, 20 ml of a dichloromethane solution containing 0.025 mol of germanyl trichloropropionyl chloride was added dropwise to a solution of 40 ml of dichloromethane containing 0.05 mol of 8-hydroxyquinoline, stirred and reacted for 5 hours, and the solvent was removed by rotary evaporation, and the remaining Add 20ml of tetrahydrofuran solvent to the mixture and wash it. After the lotion is frozen, a yellow solid is precipitated, which is collected and fully washed with cold tetrahydrofuran solvent.

[0020] The solid was dissolved in 5ml of water, and after 3 minutes, the aqueous solution was transferred to 50ml of acetone at 0-5°C, stirred for 10 minutes, the precipitate was collected by filtration, rinsed with cold water, ethanol and cold acetone in turn...

Embodiment 2

[0022] Embodiment 2: synthetic quinoline ester α-methyl ethyl germanium sesquioxide

[0023]

[0024] Use α-methacrylic acid instead of acrylic acid to synthesize trichlorogermanyl-α-methacrylic acid chloride.

[0025] The experimental method and conditions are the same as those in Example 1, except that germanium trichloride α-methyl propionyl chloride is used instead of germanyl trichloride propionyl chloride, the hydrolyzate is transferred to acetone, and a light yellow viscous solid begins to appear, which solidifies after continuing to stir . The resulting product contains 1 crystal water. Yield 30%.

[0026] Structural characterization of the product: (1) Infrared spectrum: as shown in the attached figure, 1760cm -1 Vibration absorption peaks with strong ester bonds appear on the left and right, 800-900cm -1 Ge-O characteristic strong vibration absorption peak appears, 528cm -1 A strong vibrational absorption peak appears in Ge-C. (2) NMR: chemical shift δ=1.53:...

Embodiment 3

[0027] Embodiment 3: synthetic quinoline ester β-methyl ethyl germanium sesquioxide

[0028]

[0029] Use β-methacrylic acid instead of acrylic acid to synthesize trichlorogermanyl-β-methacrylic acid chloride.

[0030] The experimental method and conditions are the same as those in Example 2, except that germanyl trichloride-β-methylpropionyl chloride is used instead of germanyl chloride α-methylpropionyl chloride. The resulting product contains 1 crystal water. Yield 62%.

[0031] Structural characterization of the product: (1) Infrared spectrum: 1755cm -1 There are strong ester bond vibration absorption peaks on the left and right, 883cm -1 There is a strong vibrational absorption peak characteristic of Ge-O, 525cm -1 A strong vibrational absorption peak appears in Ge-C. (2) NMR: chemical shift δ=1.51:3H, multiplet, -CH 3 ; δ=2.72:2H, triplet, -CH 2 ; δ=3.2-3.7:1H, multiplet, -CH; δ=7.2-8.0:6H, multiplet, quinoline hydrogen. (3) Elemental analysis C 26 h 26 N 2...

technical field

[0001] The invention belongs to an organic germanium quinoline ester compound and a synthesis method thereof. Background technique

[0002] Since 1968, Japanese scholar Asai Yiyan and others have synthesized water-soluble β-carboxyethyl germanium sesquioxide-(GeCH 2 CH 2 COOH) 2 o 3 , that is, Ge-132, and since its anti-cancer, anti-virus, anti-aging and other biological effects were discovered, the synthesis of new organic germanium compounds and the research on anti-cancer activity have become an important field for people to develop high-efficiency and low-toxicity anti-cancer drugs. People have synthesized many Ge-132 derivatives, containing -GeO 3 Various types of organic germanium compounds, such as Ge-132 analogues of the group, bridge oxygen germanium ring compounds, etc., have studied their anticancer effects in many aspects. Since the 1970s, Japan, the United States, the former Soviet Union, China and other countries have successively synthesiz...

Examples

Embodiment 1

[0016] Embodiment 1: synthetic quinoline ester ethyl germanium sesquioxide

[0017]

[0018] First, trichlorogermanyl propionyl chloride was synthesized according to the literature method.

[0019] Under cooling in an ice bath, 20 ml of a dichloromethane solution containing 0.025 mol of germanyl trichloropropionyl chloride was added dropwise to a solution of 40 ml of dichloromethane containing 0.05 mol of 8-hydroxyquinoline, stirred and reacted for 5 hours, and the solvent was removed by rotary evaporation, and the remaining Add 20ml of tetrahydrofuran solvent to the mixture and wash it. After the lotion is frozen, a yellow solid is precipitated, which is collected and fully washed with cold tetrahydrofuran solvent.

[0020] The solid was dissolved in 5ml of water, and after 3 minutes, the aqueous solution was transferred to 50ml of acetone at 0-5°C, stirred for 10 minutes, the precipitate was collected by filtration, rinsed with cold water, ethanol and cold acetone in turn...

Embodiment 2

[0022] Embodiment 2: synthetic quinoline ester α-methyl ethyl germanium sesquioxide

[0023]

[0024] Use α-methacrylic acid instead of acrylic acid to synthesize trichlorogermanyl-α-methacrylic acid chloride.

[0025] The experimental method and conditions are the same as those in Example 1, except that germanium trichloride α-methyl propionyl chloride is used instead of germanyl trichloride propionyl chloride, the hydrolyzate is transferred to acetone, and a light yellow viscous solid begins to appear, which solidifies after continuing to stir . The resulting product contains 1 crystal water. Yield 30%.

[0026] Structural characterization of the product: (1) Infrared spectrum: as shown in the attached figure, 1760cm -1 Vibration absorption peaks with strong ester bonds appear on the left and right, 800-900cm -1 Ge-O characteristic strong vibration absorption peak appears, 528cm -1 A strong vibrational absorption peak appears in Ge-C. (2) NMR: chemical shift δ=1.53:...

Embodiment 3

[0027] Embodiment 3: synthetic quinoline ester β-methyl ethyl germanium sesquioxide

[0028]

[0029] Use β-methacrylic acid instead of acrylic acid to synthesize trichlorogermanyl-β-methacrylic acid chloride.

[0030] The experimental method and conditions are the same as those in Example 2, except that germanyl trichloride-β-methylpropionyl chloride is used instead of germanyl chloride α-methylpropionyl chloride. The resulting product contains 1 crystal water. Yield 62%.

[0031] Structural characterization of the product: (1) Infrared spectrum: 1755cm -1 There are strong ester bond vibration absorption peaks on the left and right, 883cm -1 There is a strong vibrational absorption peak characteristic of Ge-O, 525cm -1 A strong vibrational absorption peak appears in Ge-C. (2) NMR: chemical shift δ=1.51:3H, multiplet, -CH 3 ; δ=2.72:2H, triplet, -CH 2 ; δ=3.2-3.7:1H, multiplet, -CH; δ=7.2-8.0:6H, multiplet, quinoline hydrogen. (3) Elemental analysis C 26 h 26 N 2...

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