Amino acid methylcyclopentenolone ester potential fragrance compound and synthesis method and application thereof

Abstract

The application discloses an amino acid methylcyclopentenolone ester potential fragrance compound and a synthesis method and application thereof, and a chemical structure general formula is The synthesis method is that, with a substituted amino acid and methylcyclopentenolone as starting materials, under the action of a condensing agent and a catalyst, condensation of the carboxyl group of the amino acid and the hydroxyl group of the methylcyclopentenolone occurs, to generate the amino acid methylcyclopentenolone ester potential fragrance compound. The compound prepared in the application is stable in chemical properties, weak in volatility, and can release the pyrolysis sweet-smelling substance methylcyclopentenolone after pyrolysis, and can obviously improve the smoking quality when added into cigarettes.

Description

Technical Field

[0001] This invention belongs to the field of novel subtle fragrance preparation, specifically relating to an amino acid methylcyclopentenol ketone ester subtle fragrance compound and its synthesis method and application. Background Technology

[0002] Caramel-sweet aroma compounds are a class of flavoring compounds that can reduce bitterness and sourness while increasing sweetness and roasted aroma. In 1971, Elmenhorst first discovered maltol, which possesses a caramel-sweet aroma, in cigarette condensate (Acta Chemica Scandinavica, 1990, 44: 916-926). Subsequently, tobacco companies in Japan and Sweden conducted in-depth research on the caramel-sweet aroma in cigarettes, successively discovering compounds with caramel-sweet characteristics such as furans, furanones, cyclopentenones, and pyranones. Among these, methylcyclopentenolone, furaneol, and ethyl maltol are the most important. These caramel-sweet aroma raw materials have been widely used in sweet flavorings (beverages, candies, chocolates, dairy products, etc.), savory flavorings (meat products, etc.), and tobacco flavorings. These compounds exist in tobacco as latent aroma compounds in the form of glycosides, esters, and other structures.

[0003] Amino acids are an important class of nitrogen-containing compounds in tobacco, and their content affects the quality of tobacco. They are also important aroma precursors (Analytical Testing Technology and Instruments, 2019, 25:48-52). There are more than 20 common amino acids in tobacco. During the combustion of tobacco, they can undergo Maillard reactions with reducing sugars to produce a variety of heterocyclic compounds such as pyran, pyrazine, pyrrole, and pyridine, which have the characteristics of cooking, roasting, and popcorn aromas. Some amino acids, such as phenylalanine, can also decompose into aroma compounds, such as benzyl alcohol and phenylethanol.

[0004] Latent aroma compounds are a class of compounds that have no aroma or a weak aroma on their own, but release aroma components when decomposed or cleaved by methods such as enzymes or heating (Recent advances in tobacco science, 1981, 7, 107-153; Australian Journal of Chemistry, 1989, 42: 2071-2084). Latent aroma compounds are characterized by low volatility and chemical stability under natural conditions. When added to cigarettes, they exist in a stable, odorless state when the cigarette is not burned. When the cigarette is burned, they cleave and release the desired aroma substances, and the amount of aroma released remains consistent throughout the burning process, thus achieving a stable aroma compensation effect. Therefore, the application of latent aroma compounds in cigarette flavoring not only solves the shortcomings of conventional flavorings and fragrances, but also allows for a certain degree of secrecy in cigarette flavor formulation. This is something that traditional flavoring techniques cannot achieve, meeting the needs of the development of low-tar cigarette products. Summary of the Invention

[0005] The purpose of this invention is to provide an amino acid methylcyclopentenolone ester-type latent aroma compound. This type of compound is chemically stable and has low volatility. After pyrolysis, it releases methylcyclopentenolone. When applied to cigarette products, it can impart a sweet and caramel aroma to cigarettes and improve their sensory quality.

[0006] Another objective of this invention is to provide a method for synthesizing amino acid methylcyclopentenolone ester-type latent fragrance compounds. This method involves synthesizing novel amino acid methylcyclopentenolone ester-type latent fragrance compounds by condensing amino acids with methylcyclopentenolone.

[0007] To achieve its objectives, the present invention employs the following technical solution:

[0008] This invention provides an amino acid methylcyclopentenol ketone ester-type aroma compound, the general structural formula of which is as follows:

[0009]

[0010] Wherein: R is hydrogen, methyl, isopropyl, sec-butyl, hydroxymethyl, 1-hydroxyethyl, mercaptomethyl, (methylthio)ethyl, carboxymethyl, carboxyethyl, carbamoylmethyl, carbamoylethyl, imidazolylmethyl, guanidinopropyl, benzyl or 4-hydroxybenzyl, (3-indolyl)methyl; R' is hydrogen, alkyl, aryl or alkoxycarbonyl.

[0011] Typical structural formulas 1-2 of the amino acid methylcyclopentenol ketone ester aroma compounds in this invention are as follows:

[0012]

[0013] The synthesis method of the above-mentioned amino acid methylcyclopentenolone ester latent fragrance compounds is as follows: using substituted amino acids and methylcyclopentenolone as starting materials, under the action of a condensing agent and a catalyst, the carboxyl group of the amino acid and the hydroxyl group of the methylcyclopentenolone undergo condensation to generate amino acid methylcyclopentenolone ester latent fragrance compounds. The structural formula of the substituted amino acid is as follows. The structural formula of the methylcyclopentenolone compound is as follows: Specifically, the steps include the following:

[0014] Step 1: Dissolve the substituted amino acid and methylcyclopentenolone in an organic solvent, add a condensing agent and a catalyst, and react at 25-100°C for 1-24 hours. Monitor the conversion of the reaction raw materials by thin-layer chromatography.

[0015] Step 2: After the reaction is complete, filter the solution, rinse the filter layer with organic solvent, evaporate the filtrate to dryness using a rotary evaporator, and then purify it by column chromatography to obtain the target product.

[0016] Further, in step 1, each 5-7 mmol of substituted amino acid reacts with 5 mmol of methylcyclopentenolone, using 5-10 mmol of condensing agent, 0.05-0.5 mmol of catalyst, and 25-50 mL of organic solvent.

[0017] Further, in step 1, the condensing agent is at least one of dicyclohexylcarbodiimide, diisopropylcarbodiimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, more preferably dicyclohexylcarbodiimide.

[0018] Further, in step 1, the catalyst is at least one of 4-dimethylaminopyridine and 4-pyrrolidinylpyridine, more preferably 4-dimethylaminopyridine.

[0019] Further, in step 1, the organic solvent is at least one selected from ethyl acetate, acetonitrile, dichloromethane, 1,2-dichloroethane, chlorobenzene, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, and methyl tert-butyl ether, more preferably dichloromethane.

[0020] Further, in step 2, the column chromatography separation refers to column chromatography under air pressure, with silica gel of 200-300 mesh, and the eluent being a mixture of petroleum ether and ethyl acetate in a volume ratio of 100-1:1 or a mixture of dichloromethane and methanol in a volume ratio of 100-10:1.

[0021] For example, when dichloromethane is used as the organic solvent, and dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) are used as the condensing agent and catalyst, the reaction formula is as follows:

[0022]

[0023] When used, the amino acid methylcyclopentenol ketone ester latent aroma compound of the present invention can be dissolved in an alcohol or alcohol-water mixture and then uniformly sprayed onto tobacco shreds or papermaking sheets. The amount of the latent aroma compound added accounts for 0.0001%-0.1% of the weight of the tobacco shreds or papermaking sheets, more preferably 0.001%.

[0024] The beneficial effects of this invention are reflected in:

[0025] 1. This invention organically combines amino acids with methylcyclopentenolone to synthesize a novel amino acid ester flavoring based on methylcyclopentenolone for the first time. When added to cigarettes as a tobacco flavoring agent, it can enhance the richness of cigarette aroma, impart a sweet and herbal aroma to cigarettes, increase the concentration of smoke, and have a significant impurity suppression effect.

[0026] 2. The synthesis method involved in this invention is simple to operate, has little environmental pollution, low production cost, and is easy to industrialize, making it a production process with great industrial application prospects.

[0027] 3. Compared with methylcyclopentenolone, amino acid methylcyclopentenolone esters exhibit significantly improved thermal stability. Specifically, the thermal decomposition temperature of Boc-L-proline methylcyclopentenolone ester increased from 114℃ to 153℃, and the maximum thermal weight loss temperature increased from 151℃ to 231℃; the thermal decomposition temperature of Boc-L-phenylalanine methylcyclopentenolone ester increased from 114℃ to 183℃, and the maximum thermal weight loss temperature increased from 151℃ to 318℃. This indicates that amino acid methylcyclopentenolone esters have a more stable structure, are less prone to oxidation and deterioration, and release the caramel-sweet aroma compound methylcyclopentenolone during combustion and pyrolysis, significantly improving the sensory quality of cigarettes. Attached Figure Description

[0028] Figure 1 Boc-L-proline methylcyclopentenolone ester 1 H NMR spectrum.

[0029] Figure 2 Boc-L-proline methylcyclopentenolone ester 13 C10 NMR spectrum.

[0030] Figure 3 Boc-L-phenylalanine methylcyclopentenolone ester 1 H NMR spectrum.

[0031] Figure 4 Boc-L-phenylalanine methylcyclopentenolone ester 13 C10 NMR spectrum.

[0032] Figure 5 The thermogravimetric analysis (TG-DTG) plots of methylcyclopentenolone, Boc-L-proline methylcyclopentenolone ester and Boc-L-phenylalanine methylcyclopentenolone ester are shown, where (a) is the TG curve and (b) is the DTG curve.

[0033] Figure 6 This is the GC spectrum of the thermal decomposition product of Boc-L-proline methylcyclopentenolone ester at 300℃.

[0034] Figure 7 This is the GC spectrum of the thermal decomposition product of Boc-L-phenylalanine methylcyclopentenolone ester at 300℃. Detailed Implementation

[0035] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings and examples. The following content is merely illustrative and explanatory of the concept of the present invention. Those skilled in the art can make various modifications or additions to the described specific embodiments or use similar methods to replace them, as long as they do not deviate from the inventive concept or exceed the scope defined by the claims, all of which should fall within the protection scope of the present invention.

[0036] Example 1: Preparation of Boc-L-proline methylcyclopentenolone ester

[0037]

[0038] In a round-bottom flask, Boc-L-proline (1.8571 g, 7 mmol, 1.4 equiv) and methylcyclopentenolone (0.5607 g, 5 mmol, 1 equiv) were added sequentially, followed by dichloromethane (25 mL), then dicyclohexylcarbodiimide (1.4443 g, 7 mmol, 1.4 equiv) and 4-dimethylaminopyridine (0.0244 g, 0.2 mmol, 0.04 equiv). The reaction was carried out at room temperature for 3 h. After the reaction was complete, the mixture was filtered, the filter cake was washed with dichloromethane, and the filtrate was collected. The solvent was removed from the filtrate using a rotary evaporator, and the mixture was separated by column chromatography (PE:EA = 6:1). 1.5149 g of the compound Boc-L-proline methylcyclopentenolone ester was obtained, with a yield of 98%. 1HNMR(600MHz,Chloroform-d)δ4.44(td,J=8.8,4.2Hz,1H),3.60–3.36(m,2H),2.55(dt,J=12.9,4.1Hz,2H),2.45–2. 37(m,2H),2.36–2.21(m,2H),1.98(d,J=12.4Hz,3H),1.89(ddtd,J=11.7,6.9,4.7,2.3Hz,1H),1.43(d,J=2.1Hz,9H); 13 C NMR(150MHz,Chloroform-d)δ199.56(199.18),169.90(169.84),161.49(160.43),154.25(153.62),145.88(145.73),80.04(79 .69),58.68(58.63),46.62(46.32),32.45(32.38),31.31(30.26),28.34(28.20),27.82(27.79),24.33(23.38),15.03(15.00). HRMS(ESI)m / z[M+H] + Calcdfor C 16 H 24 NO5:310.1649; Found:310.1645.

[0039] Example 2: Preparation of Boc-L-phenylalanine methylcyclopentenolone ester

[0040]

[0041] In a round-bottom flask, Boc-L-phenylalanine (1.2915 g, 6 mmol, 1.2 equiv) and methylcyclopentenolone (0.5607 g, 5 mmol, 1 equiv) were added sequentially, followed by dichloromethane (25 mL), then dicyclohexylcarbodiimide (1.2380 g, 6 mmol, 1.2 equiv) and 4-dimethylaminopyridine (0.0244 g, 0.2 mmol, 0.04 equiv). The reaction was carried out at room temperature for 3 h. After the reaction was complete, the mixture was filtered, the filter cake was washed with DCM, and the filtrate was collected. The solvent was removed from the filtrate using a rotary evaporator, and the product was separated by column chromatography (PE:EA = 6:1). 1.6163 g of the compound Boc-L-phenylalanine methylcyclopentenolone ester was obtained, with a yield of 90%. 1H NMR(600MHz,Chloroform-d)δ7.33–7.17(m,5H),4.96(d,J=8.3Hz,1H),4.74(q,J=6.9Hz,1H),3.29(dd,J=14 .1,5.8Hz,1H),3.17(dd,J=14.2,6.9Hz,1H),2.61–2.54(m,2H),2.50–2.43(m,2H),1.95(s,3H),1.40(s,9H); 13 C NMR(151MHz,Chloroform-d)δ203.92,175.93,155.28,149.23,146.44,135.9 4,129.40,128.51,126.96,80.09,54.19,37.87,32.04,28.27,27.28,14.45. HRMS(ESI)m / z[M+H] + Calcd for C 20 H 26 NO5:360.1806; Found:360.1804.

[0042] Example 3: Comparison of thermal stability

[0043] Depend on Figure 5 It was found that methylcyclopentenolone began to decompose at 114℃, exhibiting significant weight loss in the temperature range of 114-180℃, with the maximum weight loss rate at 151℃, reaching a total weight loss rate of 97.8%. Boc-L-proline methylcyclopentenolone ester began to decompose at 153℃, exhibiting significant weight loss in the temperature range of 153-287℃, with the maximum weight loss rate at 231℃, reaching a total weight loss rate of 99.1%; Boc-L-phenylalanine methylcyclopentenolone ester began to decompose at 183℃, exhibiting significant weight loss in the temperature range of 183-328℃, with the maximum weight loss rate at 318℃, reaching a total weight loss rate of 99.3%. The data shows that, compared with methylcyclopentenolone, the thermal decomposition temperatures of Boc-L-proline methylcyclopentenolone ester and Boc-L-phenylalanine methylcyclopentenolone ester increased from 114℃ to 153℃ and 183℃ respectively, indicating a significant improvement in thermal stability. Furthermore, the maximum thermal weight loss temperatures increased from 151℃ to 231℃ and 318℃ respectively, which are close to the operating temperatures for heating non-combustible cigarettes. This suggests that they have potential application value in the formulation design of such tobacco products.

[0044] Example 4: Pyrolysis products of the target product

[0045] Accurately weigh 2 mg of Boc-L-proline methylcyclopentenolone ester and place it in a pyrolysis apparatus. Under a helium atmosphere, rapidly heat to 300 °C at a rate of 20 °C / ms, and analyze the pyrolysis products. Replace the sample with Boc-L-phenylalanine methylcyclopentenolone ester and repeat the above operation. The total ion chromatograms of the pyrolysis products of the two amino acid methylcyclopentenolone ester compounds are shown below. Figure 6 , Figure 7 The analysis results showed that both compounds could effectively release methylcyclopentenolone (marked by arrows in the figure) at 300℃, which has a caramel sweet aroma.

[0046] Example 5: Evaluation of the flavoring effect of the target product in tobacco

[0047] The two amino acid methylcyclopentenol ketone esters, classified as latent aroma compounds, were dissolved in 95% ethanol to prepare a 0.1% (w / w) solution. 1.0 g of this solution was evenly sprayed onto 100 g of blank tobacco. After standing for 2 hours, the tobacco was rolled into sample cigarettes. The sample cigarettes were then placed in a constant temperature and humidity chamber at 22℃±1℃ and 60%±2% for 48 hours to equilibrate. A sensory evaluation was then conducted, comparing the sample cigarettes with an unflavored sample placed under the same conditions. The sensory evaluation results are shown in the table below.

[0048]

[0049]

[0050] The above are merely exemplary embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A latent fragrance compound of the amino acid methylcyclopentenol ketone class, characterized in that, The amino acid methyl cyclopentenol ketone ester type of aroma compound is Boc-L-proline methyl cyclopentenol ketone ester with the structural formula as shown in Formula 1 or Boc-L-phenylalanine methyl cyclopentenol ketone ester with the structural formula as shown in Formula 2. ； 。 2. A method for synthesizing the amino acid methylcyclopentenol ketone ester aroma compound according to claim 1, characterized in that: Using substituted amino acids and methylcyclopentenolone as starting materials, under the action of condensing agents and catalysts, the carboxyl groups of amino acids and the hydroxyl groups of methylcyclopentenolone undergo condensation to generate amino acid methylcyclopentenolone ester aroma compounds; wherein the substituted amino acid is Boc-L-proline or Boc-L-phenylalanine.

3. The synthesis method according to claim 2, characterized in that: The structural formula of the methylcyclopentenolone is: .

4. The synthesis method according to claim 2, characterized in that, Includes the following steps: The substituted amino acid, methylcyclopentenolone, condensing agent, catalyst and organic solvent are mixed and reacted at 25-100°C for 1-24 hours. After the reaction is completed, the target product is obtained by column chromatography separation and purification.

5. The synthesis method according to claim 2 or 4, characterized in that: Each 5–7 mmol of substituted amino acid is reacted with 5 mmol of methylcyclopentenolone using 5–10 mmol of condensing agent, 0.05–0.5 mmol of catalyst, and 25–50 mL of organic solvent.

6. The synthesis method according to claim 2 or 4, characterized in that: The condensing agent is at least one of dicyclohexylcarbodiimide, diisopropylcarbodiimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.

7. The synthesis method according to claim 2 or 4, characterized in that: The catalyst is at least one of 4-dimethylaminopyridine and 4-pyrrolidinylpyridine.

8. The synthesis method according to claim 4, characterized in that: The organic solvent is at least one selected from ethyl acetate, acetonitrile, dichloromethane, 1,2-dichloroethane, chlorobenzene, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, and methyl tert-butyl ether.

9. The synthesis method according to claim 4, characterized in that: The column chromatography separation refers to column chromatography under air pressure, with silica gel of 200-300 mesh, and the eluent being a mixture of petroleum ether and ethyl acetate in a volume ratio of 100-1:1 or a mixture of dichloromethane and methanol in a volume ratio of 100-10:

1.

10. The use of the amino acid methylcyclopentenol ketone ester latent aroma compound of claim 1 in cigarettes.

11. The application according to claim 10, characterized in that: The amino acid methylcyclopentenol ketone ester latent aroma compound is dissolved in an alcohol or alcohol-water mixture, and then uniformly sprayed onto tobacco shreds or papermaking sheets. The amount of the latent aroma compound added is 0.0001%-0.1% of the weight of the tobacco shreds or papermaking sheets.

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