Technology for semisynthesis of phloretin from natural phlorizin

Abstract

The invention relates to a technology for semisynthesis of a whitening and anti-skin cancer active ingredient phloretin from natural phlorizin. The technology includes: placing a phlorizin crude product in a stainless steel reaction kettle, dissolving the phlorizin crude product in a 5% strong alkaline solution, conducting simple refining and filtration to obtain a phlorizin salt solution, shifting the phlorizin salt solution into a jacket-equipped enamel reaction kettle, and adding Lewis acid and a metal catalyst at low temperature to let them react for 10-15h at 35DEG C, then lowering the temperature to 0DEG C to perform crystallization, carrying out pumping filtration and deionized water washing to obtain a phloretin coarse grain, then dissolving the coarse grain in a 95% ethanol solution, conducting fine filtration, concentration and cooling crystallization, then performing pumping filtration and drying, thus obtaining a high quality phloretin fine product with content and purity both greater than 99.0%. The technology is suitable for large-scale industrial production.

Description

technical field

[0001] The present invention relates to a semi-synthesis of phloretin, a cosmetic raw material drug capable of resisting skin tumors and preventing the generation of brown pigment, in particular to the synthesis raw material of natural polyphenol phloridin extracted from apples, apple bark and leaves. Phloretin was obtained by desugaring under Lewis acid and metal catalyst conditions, followed by separation and purification. Background technique

[0002] Phloretin, chemical name 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)-1-propanone, is an unsaturated carboxylic acid derivative of polyhydric phenols, It has various activities such as anti-oxidation, anti-ultraviolet, prevention of diabetes, anti-microbial and anti-skin cancer, etc., especially in preventing the aggregation and production of brown pigment and anti-skin tumor, which is much better than other such natural activities. This is also one of the most commonly used ingredients in high-grade white...

Examples

Embodiment 1

[0022] The synthesis of embodiment 1 phloretin

[0023] 50.0kg of crude phloridin (the content of phloridin is about 90%), in a 500L stainless steel reaction kettle, add about 300 liters of 5% sodium hydroxide solution, stir at room temperature to dissolve phloridin, after about 1h, vacuum filter , The filtrate was transferred to another 500L enamel reaction kettle. Stir and put ice salt water in the jacket to cool down. When the temperature in the reactor drops below 5°C, slowly add about 1.9L of boron trifluoride ether solution, the pH value is about 1.5, and the process control temperature is not higher than 10°C . Then continue to add 0.6 kg of nickel chloride hexahydrate at one time, and gradually raise the temperature to 35° C., stir and react for 12 hours, monitor the disappearance of phlorizin spots by thin-layer chromatography, and consider the reaction as complete. After the reaction was completed, the temperature was lowered to 0°C, and the stirring was continued,...

Embodiment 2

[0024] The synthesis of embodiment 2 phloretin

[0025] 50.0kg of crude phloridin (the content of phloridin is about 90%), in a 500L stainless steel reaction kettle, add about 300 liters of 5% sodium hydroxide solution, stir at room temperature to dissolve phloridin, after about 1h, vacuum filter , The filtrate was transferred to another 500L enamel reaction kettle. Stir and cool the jacket with ice-salt water. When the temperature in the reactor drops below 5°C, slowly add about 1.6L of phosphorus tribromide, the pH value is about 1, and the process control temperature is not higher than 10°C. Then continue to add 0.4 kg of ferric chloride at one time, and gradually raise the temperature to 35° C., stir and react for 15 hours, monitor the disappearance of phlorizin spots by thin-layer chromatography, and consider the reaction as complete. After the reaction was completed, the temperature was lowered to 0°C, and the stirring was continued, and phloretin crystals were graduall...

Embodiment 3

[0026] Embodiment 3 Phloretin is refined

[0027] Heat and dissolve 40.0kg of phloretin coarse crystals with 400L of ethanol solution containing 95% content, pass through a fine filter to a 500L stainless steel crystallization tank, concentrate under reduced pressure to obtain 300L of ethanol, and then cool to 10°C to crystallize while stirring, and then crystallize after 2 hours Suffering. Then double-cone drying was used for 2 hours to obtain 31.0 kg of fine benzfluorenol, the content and purity of which were greater than 99.0%.

technical field

[0001] The present invention relates to a semi-synthesis of phloretin, a cosmetic raw material drug capable of resisting skin tumors and preventing the generation of brown pigment, in particular to the synthesis raw material of natural polyphenol phloridin extracted from apples, apple bark and leaves. Phloretin was obtained by desugaring under Lewis acid and metal catalyst conditions, followed by separation and purification. Background technique

[0002] Phloretin, chemical name 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)-1-propanone, is an unsaturated carboxylic acid derivative of polyhydric phenols, It has various activities such as anti-oxidation, anti-ultraviolet, prevention of diabetes, anti-microbial and anti-skin cancer, etc., especially in preventing the aggregation and production of brown pigment and anti-skin tumor, which is much better than other such natural activities. This is also one of the most commonly used ingredients in high-grade white...

Examples

Embodiment 1

[0022] The synthesis of embodiment 1 phloretin

[0023] 50.0kg of crude phloridin (the content of phloridin is about 90%), in a 500L stainless steel reaction kettle, add about 300 liters of 5% sodium hydroxide solution, stir at room temperature to dissolve phloridin, after about 1h, vacuum filter , The filtrate was transferred to another 500L enamel reaction kettle. Stir and put ice salt water in the jacket to cool down. When the temperature in the reactor drops below 5°C, slowly add about 1.9L of boron trifluoride ether solution, the pH value is about 1.5, and the process control temperature is not higher than 10°C . Then continue to add 0.6 kg of nickel chloride hexahydrate at one time, and gradually raise the temperature to 35° C., stir and react for 12 hours, monitor the disappearance of phlorizin spots by thin-layer chromatography, and consider the reaction as complete. After the reaction was completed, the temperature was lowered to 0°C, and the stirring was continued,...

Embodiment 2

[0024] The synthesis of embodiment 2 phloretin

[0025] 50.0kg of crude phloridin (the content of phloridin is about 90%), in a 500L stainless steel reaction kettle, add about 300 liters of 5% sodium hydroxide solution, stir at room temperature to dissolve phloridin, after about 1h, vacuum filter , The filtrate was transferred to another 500L enamel reaction kettle. Stir and cool the jacket with ice-salt water. When the temperature in the reactor drops below 5°C, slowly add about 1.6L of phosphorus tribromide, the pH value is about 1, and the process control temperature is not higher than 10°C. Then continue to add 0.4 kg of ferric chloride at one time, and gradually raise the temperature to 35° C., stir and react for 15 hours, monitor the disappearance of phlorizin spots by thin-layer chromatography, and consider the reaction as complete. After the reaction was completed, the temperature was lowered to 0°C, and the stirring was continued, and phloretin crystals were graduall...

Embodiment 3

[0026] Embodiment 3 Phloretin is refined

[0027] Heat and dissolve 40.0kg of phloretin coarse crystals with 400L of ethanol solution containing 95% content, pass through a fine filter to a 500L stainless steel crystallization tank, concentrate under reduced pressure to obtain 300L of ethanol, and then cool to 10°C to crystallize while stirring, and then crystallize after 2 hours Suffering. Then double-cone drying was used for 2 hours to obtain 31.0 kg of fine benzfluorenol, the content and purity of which were greater than 99.0%.

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