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Preparation method of steviol

The technology of steviol aglycone and alcohol aglycone is applied in the field of preparation of steviol derivatives, which can solve the problems of affecting the reaction, extremely difficult separation and purification, unstable steviol and the like, and achieves the effect of simple reaction operation.

Active Publication Date: 2018-10-26
JIANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But under acidic condition, steviol is unstable, and Wayner-Meerwein reaction takes place easily, obtains by-products such as isosteviol and double-bond isomerization product, the obtained by-product and target product are extremely difficult to separate and purify, cause the separation of steviol Difficulty
[0010] Hu Xueyi, Jiangnan University, etc. (Hu Xueyi. Stevioside was prepared by hydrolysis of steviol glycosides catalyzed by hydrochloric acid or sulfamic acid[J]. Fine Chemical Industry, 2014,31(4):539-544) Hydrolysis of steviol glycosides by hydrochloric acid catalysis , a higher yield of steviol was obtained, but this work only gave the yield of HPLC, and did not separate and confirm the hydrolysis by-products
We repeated this work and found that the products obtained by acid catalysis are not only steviol I and isosteviol I', but also the product I" of double bond isomerization. Isosteviol I' can be separated by column chromatography, However, steviol I and the product of double bond isomerization "I" are similar in polarity. After trying a variety of developing agents, they cannot be separated on the TLC plate, so it is extremely difficult to separate and purify, and it is impossible to obtain chemically pure steviol. For subsequent steviol glycosides The synthesis introduces impurities, which affect the progress of the reaction

Method used

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  • Preparation method of steviol
  • Preparation method of steviol
  • Preparation method of steviol

Examples

Experimental program
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Effect test

Embodiment 1

[0044] Embodiment 1R is the preparation of the steviol aglycone of TBDPS

[0045] (1) Dissolve 100 g of stevia rebaudiana leaf crude extract powder in 250 mL of water, heat to dissolve, and slowly add 0.833 mL of concentrated hydrochloric acid with a concentration of 12 moL / L to the system, and reflux reaction at a stable 95 ° C for 28 hours. A white solid precipitated out. The reaction solution was completely cooled to room temperature and then filtered. The filter residue was dissolved in methanol at 60°C and recrystallized in a refrigerator at low temperature. After filtration, 12 g (0.0377 mol) of aglycone mixture was obtained as a white powdery solid.

[0046] (2) Dissolve 12 g (0.0377 mol) of the white powdery solid obtained in step (1) in 50 mL of N,N-dimethylformamide, add imidazole (1.5 eq) and TBDPSCl (1.5 eq), nitrogen React for 4 hours under protection, dilute with ethyl acetate, wash the organic phase three times with water, wash with saturated sodium chloride on...

Embodiment 2

[0051] Embodiment 2: R is the preparation of steviol aglycon of methylnaphthalene

[0052] (1) Dissolve 100 g of stevia leaf crude extract powder in 250 mL of water, heat to dissolve, then slowly add 0.41 mL of hydrochloric acid to the system, and reflux reaction at a stable 95°C for 28 hours, a white solid precipitates out. After cooling to room temperature, filter, take the filter residue and dissolve it in methanol at 60°C, place it in the refrigerator for low-temperature recrystallization, and obtain 12 g (0.0377 mol) of white powdery solid after filtration.

[0053] (2) Dissolve 5.6 g (0.0176 mol) of the white powdery solid obtained in step (1) in 25 mL of N,N-dimethylformamide, add imidazole (1.5 eq) and NapCl (1.5 eq), Under the protection of nitrogen, react for 4 hours, dilute with ethyl acetate, wash the organic phase three times with water, wash with saturated sodium chloride once, dry with anhydrous sodium sulfate, and spin the solvent to obtain 6.6 g (0.0144 mol) o...

Embodiment 3

[0058] Embodiment 3R is the preparation of the steviol aglycone of TBDPS

[0059] The preparation method is the same as in Example 1, except that in step (1), 100 g of stevia leaf crude extract powder is dissolved in 150 mL of water, and 0.625 mL of concentrated hydrochloric acid is slowly added dropwise; the temperature of the reflux reaction is 94 ° C, The time for the reflux reaction is 26 hours, and the solvent for the recrystallization is methanol. The molar ratio of steviol, isosteviol and double bond isomerization product in the obtained aglycon mixture is 1:1.2:1.2.

[0060] In step (2), the mass volume ratio of the aglycon mixture and the first organic solvent is 0.24g / mL, the base is triethylamine, and the molar ratio of the aglycone mixture, triethylamine and TBDPSCl is 1:1.2:1.2;

[0061] In step (3), the molar concentration of the aglycon mixture protected by the 19-position carboxyl group in DCM is 0.3mol / L, the epoxidation reagent is 30% hydrogen peroxide, and ...

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Abstract

The invention provides a chemically pure C19-site carboxyl protected steviol derivative. The chemically pure C19-site carboxyl protected steviol derivative is obtained by carrying out acid-catalyzed hydrolysis, silication, epoxidation and reduction on stevia leaf crude extract powder in sequence to obtain a C19-site carboxyl protected steviol derivative and isosteviol of steviol, which have greatpolar difference, and separating two products by adopting a simple and easy-to-operate operation manner; after the steviol derivative is subjected to deprotection, the steviol is obtained; the derivative also can be used for distinguishing active regions of C19 and C13, so that different reaction sites can be conveniently and subsequently subjected to operation of different functional groups.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and more specifically relates to a preparation method of steviol derivatives. Background technique [0002] Stevioside is a kaurane-type diterpene disaccharide chain glycoside mixture extracted from the leaves of Stevia rebaudiana Bertoni. Its sweetness is 150-300 times that of sucrose, and it is a strong sweetener. [0003] The production of stevioside has a history of more than 20 years in my country. After more than 20 years of development, my country has become the largest producer and exporter of stevioside in the world. However, the development level of my country's stevioside industry is still relatively low Low, mainly based on the large-scale planting of stevia and the export of crude stevia sugar extract, without the ability of deep processing, and the added value of products is low. However, the added value of the crude stevioside products exported to the United States, Japan and South...

Claims

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Application Information

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IPC IPC(8): C07F7/18C07C67/10C07C69/757C07D301/00C07D303/40C07C51/09C07C51/00C07C61/35
CPCC07C51/00C07C51/09C07C67/10C07C2603/86C07D301/00C07D303/40C07F7/188C07C69/757C07C61/35
Inventor 孙建松乔治刘慧廖进喜
Owner JIANGXI NORMAL UNIV
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