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CN-122011062-A - Glucoside derivative and synthetic method and application thereof

CN122011062ACN 122011062 ACN122011062 ACN 122011062ACN-122011062-A

Abstract

The invention provides a glucoside derivative, a synthesis method and application thereof, wherein the glucoside derivative has the following structure: R 1 is selected from alpha glucoside, beta glucoside or hydroxyl, R 2 is selected from alpha glucoside, beta glucoside or hydroxyl, R 3 is alkyl, and the synthesis method comprises the steps of S1, taking pentaacetyl glucose as a raw material, obtaining tetraacetyl glucose through an amination reaction, S2, obtaining a glycosylation donor from the tetraacetyl glucose under the action of a glycosylation donor reagent, S3, obtaining a glycosylation intermediate product through a glycosylation reaction, and S4, obtaining a target product through deprotection of the glycosylation intermediate product. According to the research of the invention, R 3 is alkyl with 3 carbon atoms, which has more advantageous whitening property, and the method of the invention has the characteristics of milder and low cost.

Inventors

  • WU JIANG
  • GAO ANG
  • ZHANG WEI
  • ZHOU BAOPING
  • Han tengfei
  • ZHANG DIE
  • LAN TIANSHENG

Assignees

  • 上海克琴科技有限公司

Dates

Publication Date
20260512
Application Date
20260331

Claims (10)

  1. 1. A method for synthesizing a glucoside derivative is characterized in that: The structure of the glucoside derivative is as follows: ; r 1 is selected from alpha glucoside, beta glucoside or hydroxyl; R 2 is selected from alpha glucoside, beta glucoside or hydroxyl; r 3 is alkyl; the synthesis method comprises the following steps: s1, taking pentaacetyl glucose as a raw material, and obtaining tetraacetyl glucose through an amination reaction; s2, obtaining a glycosylation donor from the tetraacetyl glucose under the action of a glycosylation donor reagent; S3, the glycosylation donor is subjected to glycosylation reaction to obtain a glycosylation intermediate product; s4, deprotecting the glycosylation intermediate product to obtain a target product; Wherein the structural formula of the tetraacetyl glucose is shown as follows: ; the structural formula of the glycosylation donor is shown as follows: ; the structural formula of the glycosylation intermediate product is shown as follows: ; r 1 ' is Or hydroxy, R 2 ' is Or hydroxy.
  2. 2. A method of synthesizing a glucoside derivative as set forth in claim 1, wherein: The amination reaction is carried out for 25-35h at room temperature; the molar ratio of the pentaacetyl glucose to the amination reagent is 1:1-1.6.
  3. 3. A method of synthesizing a glucoside derivative as set forth in claim 1, wherein: In S2, under the protection of a protective gas, sequentially adding a glycosylation donor reagent and a catalytic activator into a reaction product of S1 at a temperature not higher than 0 ℃, and then reacting for 2.5-3.5 hours at room temperature; The molar ratio of the tetraacetyl glucose, the glycosylation donor reagent and the catalytic activator is 1:3.8-4.2:0.18-0.22.
  4. 4. A method of synthesizing a glucoside derivative as set forth in claim 1, wherein: in S3, under the protection of protective gas, adding a catalyst into a mixed system of a reaction product of S2 and 4-alkyl resorcinol at the temperature of minus 15 ℃ to minus 5 ℃ to react for 8-12 hours at the temperature of minus 8 ℃ to minus 2 ℃; the molar ratio of the glycosylation donor to the 4-alkyl resorcinol and the catalyst is 2.4-2.8:1:0.4-0.6.
  5. 5. A method of synthesizing a glucoside derivative as set forth in claim 1, wherein: In S4, adding a deprotection reagent into the reaction product of S3 at a temperature of not higher than 0 ℃, and then reacting for 6-8h at room temperature; The molar ratio of the glycosylation intermediate to the deprotection reagent is 1:0.9-1.1.
  6. 6. A method of synthesizing a glucoside derivative as set forth in claim 1, wherein: in S4, after the reaction is completed, quenching the reaction by an acidic medium; the addition amount of the acid medium is 0.6-0.8 times of the mass of the glycosylation intermediate product.
  7. 7. A glucoside derivative, characterized by the following structural formula: ; r 1 is selected from alpha glucoside, beta glucoside or hydroxyl; R 2 is selected from alpha glucoside, beta glucoside or hydroxyl; R 3 is an alkyl group having 3 carbon atoms.
  8. 8. A glucoside derivative according to claim 7, wherein the glucoside derivative is as follows: 4-propylresorcinol-1-o- α -glucoside, 4-propylresorcinol-1-o- β -glucoside, 4-propylresorcinol-1, 3-bis- α -glucoside, 4-propylresorcinol-1, 3-bis- β -glucoside, 4-isopropylresorcinol-1-o- α -glucoside, 4-isopropylresorcinol-1-o- β -glucoside, 4-propylresorcinol-1, 3-bis- α -glucoside, 4-isopropylresorcinol-1, 3-bis- β -glucoside.
  9. 9. Use of a glucoside derivative according to claim 7 for the preparation of cosmetics/skin care products.
  10. 10. Use of a glucoside derivative according to claim 7 for preparing a whitening product.

Description

Glucoside derivative and synthetic method and application thereof Technical Field The invention relates to a chemical method and a new raw material of cosmetics, in particular to a process for synthesizing a glucoside derivative, several new compounds synthesized based on the process and application of the new compounds in the field of cosmetics. Background The compound containing resorcinol structure, such as 4-butyl resorcinol, has good whitening effect in cosmetics, but the compound is easy to generate autoxidation, and has the problems of strong irritation, reduced whitening activity, easy color change, influence on the overall stability of the formula and the like. In order to solve the defects, the prior patent (CN 120173034A) discloses a whitening compound grafted with glycoside at the phenolic hydroxyl position of 4-butylresorcinol, which comprises 4-butylresorcinol-1-o-alpha-glucoside, 4-butylresorcinol-1-o-beta-glucoside and the like, wherein the compound protects hydroxyl through the steric hindrance effect of glycoside, reduces free radical generation, reduces skin irritation, can restore whitening activity through skin microecological degradation, and obviously improves the application defects of 4-butylresorcinol. However, for the synthesis process of the compound, research finds that certain limitations exist, specifically as follows: When the alpha-glucoside compound is prepared, the glycosylation donor is prepared by catalyzing and triggering the O-group participation effect by BF 3-Et2 O at the low temperature of-15 to-20 ℃, the reaction is carried out for 18 hours under the protection of argon, the reaction condition is harsh, and the energy consumption is high. When the beta-glucoside compound is prepared, the bromoglycosyl donor is prepared by reacting the fully acetylated glucose with 33% HBr/acetic acid solution, and then the bromoglycosyl donor reacts with activated 4-butylresorcinol for 24 hours at 55 ℃, the HBr/acetic acid solution with stronger corrosiveness is involved in the reaction step, the operation risk is higher, the reaction time is longer, and the production efficiency is lower. The elution system of the column chromatography purification step is not optimized enough, so that the yield and purity of the product are required to be further improved, and the industrial mass production is not facilitated. In the prior art, the cost of part of raw materials is extremely high (the lowest cost of 1 kilogram is 50 ten thousand), which is not beneficial to industrialized mass production and market popularization. Disclosure of Invention The invention aims to overcome the defects, develop a novel process for synthesizing the whitening compound, which has mild reaction conditions, simple and convenient operation, high production efficiency and controllable cost, and has important significance for promoting the large-scale application of the whitening compound. The invention discloses a method for synthesizing a glucoside derivative, The structure of the glucoside derivative is as follows: ; r 1 is selected from alpha glucoside, beta glucoside or hydroxyl; R 2 is selected from alpha glucoside, beta glucoside or hydroxyl; r 3 is alkyl; The synthesis method comprises the following steps: s1, taking pentaacetyl glucose as a raw material, and obtaining tetraacetyl glucose through an amination reaction; S2, obtaining a glycosylation donor from tetraacetyl glucose under the action of a glycosylation donor reagent; s3, glycosylation donor is subjected to glycosylation reaction to obtain a glycosylation intermediate product; S4, deprotecting the glycosylation intermediate product to obtain a target product; wherein, the structural formula of the tetraacetyl glucose is shown as follows: ; The structural formula of the glycosylation donor is shown as follows: ; The structural formula of the glycosylation intermediate is shown as follows: ; r 1' is Or hydroxy, R 2' isOr hydroxy. In the above synthesis method, the amination reaction is carried out at room temperature for 25-35 hours; the molar ratio of the pentaacetyl glucose to the amination reagent is 1:1-1.6. In S2, under the protection of a protective gas, sequentially adding a glycosylation donor reagent and a catalytic activator into a reaction product of S1 at a temperature not higher than 0 ℃, and then reacting for 2.5-3.5 hours at room temperature; The molar ratio of the tetraacetylglucose, the glycosylation donor reagent and the catalyst activator is 1:3.8-4.2:0.18-0.22. In S3, under the protection of protective gas, adding a catalyst into a mixed system of a reaction product of S2 and 4-alkyl resorcinol at the temperature of minus 15 ℃ to minus 5 ℃ to react for 8-12 hours at the temperature of minus 8 ℃ to minus 2 ℃; the molar ratio of glycosylation donor to 4-alkyl resorcinol and catalyst is 1.4-2.8:1:0.4-0.6. In S4, adding a deprotection reagent into the reaction product of S3 at a temperature of not higher than 0 ℃, and then react