CN102002028B

CN102002028B - Method for synthesizing luteolin

Info

Publication number: CN102002028B
Application number: CN2010105319208A
Authority: CN
Inventors: 王超
Original assignee: CELL MOLECULAR PHARMACEUTICAL R&D Co Ltd
Current assignee: By Xi'an Chinese Medicine Research & Development Co Ltd
Priority date: 2010-11-03
Filing date: 2010-11-03
Publication date: 2012-08-22
Anticipated expiration: 2030-11-03
Also published as: CN102002028A

Abstract

The invention discloses a method for synthesizing luteolin, comprising the following steps of: adding rutin at the room temperature of 20-30DEG C in alkali water and stirring for dissolving; adding a reducing agent of sodium hydrosulfite with equivalent weight of 6.3 once, continuously heating up to 100DEG C and stirring for 12 hours; after the HPLC (High Performance Liquid Chromatography) monitoring reaction is finished, cooling, adding dilute hydrochloric acid or dilute sulfuric acid, adjusting the pH to be 3-4, standing for 24 hours for separating out a solid and filtering; washing a filtering cake with water twice to remove salts contained in the product; and drying to obtain a crude product, continuously crystalizing with ethanol to obtain a pure product with the purity being more than 95 percent. Compared with the prior art, the invention has the advantages of high synthetic efficiency, high yield, low energy consumption, low pollution, greenness, environmental protection and the like and is easy for industrialized production.

Description

A kind of method of synthetic luteolin

Technical field

The present invention relates to the synthetic field of material, particularly relating to a kind of is the compound method of feedstock production luteolin by natural extract.

Background technology

Luteolin is an isolating identical effective constituent from Herba Dracocephali Integrifolii and Anhui Herba Ajugae, and extraction yield is very low in the prior art, is 2/10000ths, and its structure is 3 ', 4 ', 5,7-tetrahydroxy NOVASOY 400.It is reported that these article are to inflammation, tumour, allergy, struvite demyelinating disease has better curative effect.Can also suppress multiple virus.Be used to clinically at present, and be made into patent medicine.Therefore luteolin has vast market prospect.

Summary of the invention

The object of the present invention is to provide a kind of is raw material with the rutin, through the novel method of the synthetic luteolin of a step chemical reaction.

The detailed process of present method does, rutin is joined in the buck under the temperature of 20-30 degree, stirs and makes it dissolving, is warming up to the 45-50 degree; Once add 6.3 normal reductive agent vat powders then, stirred 30-45 minute, continue to be warming up to 100 degree, stirred 12 hours; The HPLC monitoring reaction finishes, and is cooled to the 20-25 degree then, then adds Hydrogen chloride or dilute sulphuric acid, transfers pH to 3-4; Left standstill 10-24 hour, and filtered, filter cake is with water washing 2 times; Oven dry obtains bullion, continues to use alcohol crystal, obtains the luteolin of purifying.

Wherein, said vat powder is preferably Na ₂S ₂O ₄

Said buck is preferably NaOH solution, and its concentration is preferably 0.15kg/L, and the mass ratio of rutin and NaOH solution is preferably 1: 20-23;

The concrete steps of said alcohol crystal are preferably: bullion is joined in the ethanol, and heating for dissolving concentrates out part ethanol, and rest solution was placed the freezing crystallization of 0-10 degree 8 hours, filters oven dry then;

Said bullion and alcoholic acid mass ratio are (5-6): 100, and the ratio that the amount of alcohol that concentrates out accounts for total amount of alcohol is 55%-60%.

Compare with existing processes, the present invention has following advantage:

1: the combined coefficient of this technology is very high, and preparing luteolin only needs a step.

2: yield is high, and the product purity of once taking just can reach 85%, and follow-up treating process is also very simple.

3: energy consumption is low, pollute little, easy for industrialized production.

4: raw materials used very safe with auxiliary material, people and animals there is not injury.Meet the requirement of Green Chemistry and atom economy.

Embodiment

Below in conjunction with specific embodiment the present invention is described further, but the present invention is not limited to following examples.

Embodiment one:

Synthetic route:

Preparation: in the there-necked flask of 1L, add 600 gram water, add the sodium hydroxide of 90 grams again, stir and make it dissolving; When the temperature of reaction flask drops to 20-30 and spends by the time, slowly add 30 gram rutins, continue to stir 30 minutes; Treat that rutin all dissolves, be warmed up to 50 degree then, add 65 gram vat powders; Under this temperature, stirred 45 minutes, be warming up to 100 degree, stirred 12 hours.The HPLC detection reaction finishes, and with the reaction flask cooling, between the 20-25 degree, splashes into Hydrogen chloride or dilute sulphuric acid, transfers pH to 3-4, leaves standstill then 10 hours, filters, and washing, oven dry obtain the thick luteolin of 11.5 grams.

Refining: the thick luteolin of 11.5 grams is joined in the 200 gram ethanol, and heating for dissolving concentrates out 120 gram ethanol then; Rest solution was placed the freezing crystallization of 0-10 degree 8 hours, filter then, the washing with alcohol that filter cake restrains with 20 of freezing mistake once; Oven dry obtains 9 gram products.HPLC detects purity 96.3%.

Embodiment two:

Preparation: the 500L glassed steel reaction vessels is cleaned, in still, added 300 kg of water, add 45 kilograms of sheet alkali again, open cooling water temperature temperature is dropped to below 25 degree, divide 3 batches to add 15 kilograms of rutins, stirred then 1 hour, rutin is all dissolved.Be warming up to the 45-50 degree then, slowly add 32.5 kilograms of vat powders, under this temperature, stirred 30 minutes; Be warming up to then and refluxed 12 hours, below cooling reaction still to 20 degree, splash into Hydrogen chloride to pH to 3-4; Left standstill then 10 hours; Cross filter press, the product that obtains with water washing is once dried and is obtained 6 kilograms of luteolins.

Refining: 6 kilograms of luteolins are dissolved in 100 kilograms of ethanol, steam 55 kilograms of ethanol then, rest solution is cooled to the 0-5 degree, leave standstill 10 hours crystallizatioies, obtain 4 kilograms of purity and be 95.6% luteolin, yield is 56.5%.

Claims

1. the method for a synthetic luteolin, it is characterized in that: preparation process comprises:

Rutin is joined in the buck under the temperature of 20-30 degree, stir and make it dissolving, be warming up to the 45-50 degree, once add 6.3 normal reductive agent vat powders then, stirred 30-45 minute; Continue to be warming up to 100 degree, stirred 12 hours, the HPLC monitoring reaction finishes, and is cooled to the 20-25 degree then; Then add Hydrogen chloride or dilute sulphuric acid, adjust pH left standstill 10-24 hour to 3-4, filtered; Filter cake is with water washing 2 times, and oven dry obtains bullion, continues to use alcohol crystal, obtains the luteolin of purifying; Wherein said vat powder is Na ₂S ₂O ₄Said buck is a NaOH solution, and its concentration is 0.15kg/L, and the mass ratio of rutin and NaOH solution is 1: 20-23; The concrete steps of said alcohol crystal are: bullion is joined in the ethanol, and heating for dissolving concentrates out part ethanol, and rest solution was placed the freezing crystallization of 0-10 degree 8 hours, filters oven dry then; Said bullion and alcoholic acid mass ratio are (5-6): 100, and the ratio that the amount of alcohol that concentrates out accounts for total amount of alcohol is 55%-60%.