Linalool glycosylation derivative as well as preparation and application thereof

Abstract

The invention discloses a linalool glycosylation derivative as well as preparation and application thereof. The structure of the linalool glycosylation derivative is shown as a formula (I), R1, R2, R3, R4 and R5 groups are independently selected from H or a linalool group, and the preparation method comprises the following steps: taking linalool and glucose as raw materials, and catalytically synthesizing the linalool glycosylation derivative by using beta-glucosidase under an acidic heating condition. According to the linalool glycosylation derivative, the water solubility, the antibacterial property, the stability and the fragrance durability of the linalool glycosylation derivative are greatly improved by introducing the glucosyl group into the linalool. The derivative is suitable for various daily chemical products with antibacterial properties, and has a better industrial application prospect.

Description

Technical Field

[0001] This invention relates to a linalool derivative and its preparation method, and more particularly to a linalool glycosylated derivative and its preparation and application. Background Technology

[0002] Linalool, a naturally occurring organic compound with an aromatic scent, has long been a focus of attention in the fields of fragrance, pharmaceuticals, and cosmetics. However, as a terpene compound, while its molecule contains hydroxyl groups and exhibits some hydrophilicity, its relatively long carbon chain and unsaturated double bonds result in it being only slightly soluble in water. This poor water solubility significantly limits its applications in water-based media. For example, in the preparation of water-based disinfectants, cleaning agents, or certain pharmaceutical formulations, its low water solubility makes it difficult to achieve ideal concentrations and uniform dispersion, thus affecting product performance and efficacy. Furthermore, although linalool possesses a certain fragrance, its high volatility and direct, pronounced aroma, coupled with its small molecular weight and high volatility, result in a short-lasting scent and may cause discomfort to some individuals.

[0003] Existing technologies typically employ simple physical mixing methods to improve the water solubility and odor of linalool, such as simply mixing linalool with other water-soluble additives like ethanol. While convenient, this often results in poor stability, limited flavor improvement, and short-lasting effects. Introducing hydrophilic groups through chemical or biological modifications can increase the water solubility of linalool, but these groups do not improve its poor aroma persistence and stability. Furthermore, incorrectly introducing hydrophilic groups can decrease the antibacterial properties of linalool, hindering its application in antibacterial products. Currently, there are no reports of using glycosylation modification to simultaneously improve the water solubility, antibacterial properties, stability, and aroma persistence of linalool. Summary of the Invention

[0004] Objectives of this invention: The objective of this invention is to provide a linalool glycosylation derivative, addressing the problem of simultaneously improving the water solubility, antibacterial properties, stability, and fragrance persistence of linalool. A second objective is to propose a method for preparing the linalool glycosylation derivative, addressing the problem of how to prepare such derivatives. A third objective is to propose the application of the linalool glycosylation derivative in the preparation of daily chemical products with antibacterial or bactericidal functions, addressing the problem of how to prepare such products.

[0005] Technical solution: The linalool glycosylation derivative of the present invention has the following structural formula:

[0006]

[0007] Among them, the R1, R2, R3, R4, and R5 groups are independently selected from H or

[0008] Preferably, the R1 group is The R2, R3, R4, and R5 groups are all H.

[0009] This invention reduces the volatility of linalool by introducing glucose groups into it. Under specific conditions (such as enzymatic hydrolysis on the skin surface, acidic environment, or heating), the glycosidic bonds break, producing a "slow-release fragrance," thus avoiding the irritation or volatility problems associated with directly using linalool. The glucose groups in the glycosylated linalool derivatives contain multiple hydroxyl groups, which can form hydrogen bonds with water molecules, thereby greatly improving the solubility of linalool glucoside in water.

[0010] The second aspect of this invention discloses a method for preparing the above-mentioned linalool glycosylation derivative, comprising the following steps:

[0011]

[0012] Among them, the R1, R2, R3, R4, and R5 groups are independently selected from H or

[0013] Preferably, the enzyme is β-glucosidase, and the solvent is alcohol.

[0014] Furthermore, the alcohol is selected from at least one of butanol, pentanol, and hexanol.

[0015] Preferably, the reaction conditions are: stirring at 30-50°C for 2-6 hours under acidic conditions.

[0016] Furthermore, the acidic conditions are defined as a pH range of 4.5-6.0.

[0017] During the reaction, linalool and glucose combine via glycosidic bonds (O-glycosidic bonds) under glycosyltransferase conditions, undergoing glycosylation. The hydroxyl group of linalool undergoes a dehydration condensation reaction with the hemiacetal hydroxyl group of glucose, forming linalool glucoside. This process requires enzymatic catalysis. The main enzymes are glycosyltransferases, such as β-glucosidases, including those derived from almonds and Aspergillus niger. The synthesis of linalool glucoside requires the catalysis of glycosyltransferases. These enzymatic reactions are sensitive to temperature and pH.

[0018] The effect of temperature on enzymatic reactions: Enzyme activity is temperature-dependent; both excessively high and low temperatures will affect the reaction rate. Too high a temperature can easily deactivate the enzyme; too low a temperature will inhibit enzyme activity and slow the reaction. The optimal temperature is 40-60℃. At this temperature, enzyme activity is high, which can accelerate the reaction rate of linalool and glucose, producing more linalool glucoside. Enzymes from different sources have different temperature requirements; for example, the activity of glycosyltransferases typically reaches its peak at 30-45℃, and the catalytic efficiency of glycosyltransferases in jasmine flowers is highest at 35℃.

[0019] The effect of pH on enzyme activity: Enzyme activity is also affected by pH. A pH range of 4.5-6.0 maintains the structural stability of the enzyme, allowing it to fully exert its catalytic activity. Excessively high or low pH values ​​can affect the structure of the enzyme's active site, reducing catalytic efficiency.

[0020] Preferably, the molar ratio of linalool to glucose is 1-1.5:1-1.5.

[0021] Preferably, the above preparation method further includes the following steps:

[0022] The reaction product of linalool and glucose was added to a mixture of n-butanol and water. After mixing and standing, the organic phase was collected for a single extraction. After repeated extraction, n-butanol was removed to obtain the linalool glycosylation derivative.

[0023] In some embodiments, the mixture of n-butanol and water is prepared by mixing n-butanol and water in a 1:1 volume ratio. In the water and n-butanol mixture, linalool glycosylation derivatives are more soluble in n-butanol, and relatively pure linalool glycosylation derivatives can be obtained after 2-5 extractions and concentrations.

[0024] The third aspect of this invention discloses the application of the above-mentioned linalool glycosylation derivatives in the preparation of daily chemical products with antibacterial or bactericidal functions.

[0025] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0026] This invention significantly improves the water solubility of linalool glycosylation derivatives by introducing glucose groups into linalool, making them more suitable for use in aqueous systems. The increased water solubility allows the linalool glycosylation derivatives to more easily contact hydrophilic microorganisms, resulting in better efficacy against Gram-negative bacteria in aquatic environments. The use of glucose groups in this invention avoids the negative impact of the modified group on the original antibacterial properties of linalool, enabling the linalool glycosylation derivatives to exhibit good inhibitory effects against common Gram-positive, Gram-negative bacteria, and fungi, demonstrating superior antibacterial performance compared to linalool itself.

[0027] Meanwhile, linalool glycosylation derivatives exhibit better stability and longer-lasting fragrance compared to linalool. They are suitable not only for sensitive skin care products, shower gels, and fabric care products requiring long-lasting fragrance, but also for perfumes or fast-evaporating fragrance products seeking immediate scent. Linalool glycosylation derivatives have a stable structure and maintain activity over a wider range of temperatures and pH values, making them suitable for a broader range of applications. Detailed Implementation

[0028] The technical solution of the present invention will be further described below.

[0029] Example 1: A linalool glycosylation derivative, with the following structural formula:

[0030]

[0031] The preparation method of the above-mentioned linalool glycosylation derivatives is as follows:

[0032]

[0033] Accurately weigh 10 mmol of linalool and 12 mmol of glucose and add them to a three-necked flask containing 50 mL of n-butanol. Then, slowly add 10 mmol of a β-glucosidase solution extracted from almonds (enzyme activity concentration 30 U / mg, Shanghai Yuanye Biotechnology Co., Ltd.: catalog number S10047-10u). After mixing, add an appropriate amount of acetic acid to maintain the pH of the reaction system at 5.0. Place the reaction system in an oil bath, heat to 40°C, and turn on the stirrer, stirring at 300 rpm for 4 hours.

[0034] After the reaction was completed, the reaction product was cooled to room temperature and added to a 1:1 mixture of n-butanol and water. After mixing and standing, the n-butanol phase was collected for a single extraction. This extraction was repeated four times. The combined n-butanol extracts were then placed in a rotary evaporator and subjected to rotary evaporation (reduced pressure distillation) under a vacuum of 0.08-0.1 MPa and a water bath temperature of 50-60℃ to remove n-butanol from the extract until no solvent was distilled off. The remaining viscous substance was the linalool glycosylation derivative. Because β-glucosidase selectively catalyzes the reaction of hydroxyl groups at a specific site (C1 position) of glucose, it can only efficiently catalyze the reaction of hydroxyl groups at this site with linalool, while other hydroxyl sites (C2-C5 positions) hardly participate in the reaction. Therefore, the final product is mainly a compound with a single structure.

[0035] The 1H NMR spectra of the above-mentioned final products are as follows:

[0036] 1¹H-NMR (DMSO-d6, 400MHz) δ: 5.81 (¹H, dd, J = 17.6, 10.8 Hz, linalool double bond H-2), 5.08 (¹H, d, J = 10.8 Hz, linalool double bond H-1a), 5.01 (¹H, d, J = 17.6 Hz, linalool double bond H-1b), 4.82 (¹H, d, J = 7.8 Hz, glucose terminal H-1', β-configuration characteristic), 4.65–4.42 (⁵H, m, glucose hydroxyl H, exchangeable), 3. 86 (1H, m, glucose H-6'a), 3.64 (1H, m, glucose H-6'b), 3.38-3.21 (4H, m, glucose H-2', 3', 4', 5'), 3.17 (1H, m, linalool H-3 on glycosidic bond), 2.01 (2H, m, linalool H-4), 1.68 (3H, s, linalool H-8, methyl group adjacent to double bond), 1.59 (2H, m, linalool H-5), 0.91 (3H, d, J = 6.8 Hz, linalool methyl group H-9).

[0037] Example 2: Everything else is the same as in Example 1, except that:

[0038] Weigh out 15 mmol of linalool and 10 mmol of glucose;

[0039] The pH of the reaction system was 6.0, the reaction temperature was 30℃, and the reaction was stirred for 6 hours.

[0040] Example 3: Everything else is the same as in Example 1, except that:

[0041] Weigh out 10 mmol of linalool and 15 mmol of glucose;

[0042] The pH of the reaction system was 4.5, the reaction temperature was 50℃, and the reaction was stirred for 2 hours.

[0043] Example 4: Everything else is the same as in Example 1, except that:

[0044] Weigh out 12 mmol of linalool and 12 mmol of glucose;

[0045] The pH of the reaction system was 5.5, the reaction temperature was 45℃, and the reaction was stirred for 3 hours.

[0046] Comparative Example 1: Everything else is the same as in Example 1, except that:

[0047] Replace glucose with β-D-fructose.

[0048] Comparative Example 2: Everything else is the same as in Example 1, except that:

[0049] Replace glucose with galactose.

[0050] The water solubility, antibacterial properties, stability, and aroma persistence of the linalool glycosylated derivatives prepared in Examples 1-4 and Comparative Examples 1-2 were tested using the following methods:

[0051] Water solubility test: Under constant temperature stirring at 25℃, an excess of linalool glycosylation derivative sample was added to 1L of deionized water, and stirring was continued until the sample no longer dissolved. The weight of the undissolved sample was measured, and the solubility of the sample in water was calculated using the following formula:

[0052] Solubility = (Initial sample addition - Undissolved sample volume) / Volume of water;

[0053] Antibacterial test: Staphylococcus aureus and Escherichia coli cultures in logarithmic growth phase were taken separately. Each linalool glycosylation derivative sample was dissolved in liquid culture medium to obtain a stock solution. The stock solution was added to the bacterial culture medium until the final sample concentration reached 2 mg / mL. The blank control group was added only with liquid culture medium. The OD of the bacterial culture at this point was measured. 600 The values ​​were all 0.23. The bacterial culture broth containing linalool glycosylation derivatives was further cultured at 37℃ for 6 hours, and the OD values ​​of each group of bacterial culture broth were measured. 600 The antibacterial rate is calculated using the following formula:

[0054] Antibacterial rate = (OD of the blank control group after culture) 600 -OD after culturing with linalool glycosylation derivative 600 ) / (OD after culture of the blank control group) 600 -0.23)×100%;

[0055] The results are as follows:

[0056] Table 1. Solubility and antibacterial properties of linalool glycosylation derivatives

[0057]

[0058] As shown in Table 1, the introduction of glucose groups can significantly improve the water solubility and antibacterial properties of linalool. While the introduction of fructose pyranose or galactose can also improve the water solubility of linalool derivatives, the introduction of fructose and galactose groups will reduce the antibacterial properties of linalool.

[0059] Stability test: Each linalool glycosylation derivative sample was dissolved in deionized water at different pH (pH adjusted by hydrochloric acid or NaOH) to a final concentration of 8 mg / mL, and then kept at a constant temperature for 72 h. The aqueous solution of the linalool glycosylation derivative after standing was then added to the Escherichia coli culture medium as a sample, and the antibacterial rate was measured.

[0060] The results are as follows:

[0061] Table 2. Stability test results of different linalool glycosylation derivatives.

[0062]

[0063]

[0064] As shown in Table 2, linalool exhibits significantly reduced antibacterial activity and poor stability under high temperature, excessively acidic, and excessively alkaline conditions. In contrast, the linalool glycosylated derivatives prepared in this invention demonstrate good stability over a wider temperature and pH range, with no significant fluctuations or decline in antibacterial activity.

[0065] Fragrance persistence test: Each linalool glycosylation derivative sample was dissolved in deionized water to a final concentration of 4 mg / mL to obtain a sample solution. The sample solution was sprayed onto fragrance paper, and under constant temperature and humidity (23±2℃), air was continuously blown onto the fragrance paper at a wind speed of 2.5 m / s. The fragrance paper was evaluated hourly until the fragrance could no longer be detected, and the duration was recorded. The longer the duration, the more persistent the fragrance. The results are as follows:

[0066] Table 3. Results of aroma persistence tests for different linalool glycosylation derivatives

[0067] Group Fragrance duration (h) Example 1 28 Example 2 25 Example 3 27 Example 4 23 Comparative Example 1 20 Comparative Example 2 18 Linalool 5

[0068] As can be seen from the results in Table 3, the present invention can significantly improve the aroma persistence of linalool, and the improvement is significantly greater than that of galactose and fructose modified derivatives.

Claims

1. A linalool glycosylation derivative, characterized in that, The structure is as follows: Among them, the R1, R2, R3, R4, and R5 groups are independently selected from H or 2. The linalool glycosylation derivative according to claim 1, characterized in that, The R1 group is The R2, R3, R4, and R5 groups are all H.

3. The method for preparing the linalool glycosylated derivative according to claim 1 or 2, characterized in that, Includes the following steps: Among them, the R1, R2, R3, R4, and R5 groups are independently selected from H or 4. The method for preparing the linalool glycosylated derivative according to claim 3, characterized in that, The enzyme is β-glucosidase, and the solvent is alcohol.

5. The method for preparing the linalool glycosylated derivative according to claim 4, characterized in that, The alcohol is selected from at least one of butanol, pentanol, and hexanol.

6. The method for preparing the linalool glycosylated derivative according to claim 3, characterized in that, The reaction conditions are: stirring at 30-50℃ for 2-6 hours under acidic conditions.

7. The method for preparing the linalool glycosylated derivative according to claim 6, characterized in that, The acidic conditions are defined as a pH range of 4.5-6.

0.

8. The method for preparing the linalool glycosylated derivative according to claim 3, characterized in that, The molar ratio of linalool to glucose is 1-1.5:1-1.

5.

9. The method for preparing the linalool glycosylated derivative according to claim 3, characterized in that, It also includes the following steps: The reaction product of linalool and glucose was added to a mixture of n-butanol and water. After mixing and standing, the organic phase was collected for a single extraction. After repeated extraction, n-butanol was removed to obtain the linalool glycosylation derivative.

10. The application of the linalool glycosylation derivative according to claim 1 or 2 in the preparation of daily chemical products with antibacterial or bactericidal functions.

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