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

Abstract

The application discloses an amino acid phenolic ester base incense compound, a synthesis method and application thereof, and a chemical structure general formula thereof is The synthesis method is as follows: taking substituted amino acid and maltol compounds as starting materials, under the action of a condensing agent and a catalyst, condensation occurs between the carboxyl group of the amino acid and the hydroxyl group of the maltol compound, and the amino acid phenolic ester base incense compound is generated. The compound prepared by the application has weak volatility, can release maltol pyrolysis sweet-smelling substances after pyrolysis, and can obviously improve smoking quality when being added into cigarettes.

Description

Technical Field

[0001] This invention belongs to the field of novel subtle fragrance preparation, specifically relating to an amino acid phenol 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 very faint aroma on their own, but release aroma components only after being 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 structural 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 phenolic ester latent aroma compound. This compound has low volatility and releases maltol substances after pyrolysis. 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 phenolic ester latent aroma compounds, wherein the method involves synthesizing novel amino acid phenolic ester latent aroma compounds by condensing amino acids and maltol compounds.

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

[0008] This invention provides an amino acid phenol 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; R” is hydrogen or methyl.

[0011] Typical structural formulas 1-5 of the amino acid phenol ester latent fragrance compounds in this invention are as follows:

[0012]

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

[0014] Step 1: Dissolve the substituted amino acids and maltol compounds in an organic solvent, add condensing agent and catalyst, and react at 25-100℃ 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 maltol compound, 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 phenolic ester latent aroma compound of the present invention can be dissolved in an alcohol or an 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 is the first to design and synthesize amino acid phenolic ester latent aroma compounds. By organically combining amino acids with maltol compounds, the stability of maltol flavorings is greatly improved. During combustion and pyrolysis, maltol caramel sweet aroma substances can be released. When added to cigarettes, it can enrich the caramel sweet aroma and significantly improve the sensory quality of cigarettes.

[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. Taking amino acid ethyl maltol ester as an example, compared with ethyl maltol, amino acid ethyl maltol ester has significantly improved thermal stability. Specifically: the thermal decomposition temperature of Boc-L-phenylalanine ethyl maltol ester increased from 117℃ to 154℃, and the maximum thermal weight loss temperature increased from 192℃ to 226℃; the thermal decomposition temperature of Boc-L-proline ethyl maltol ester increased from 117℃ to 212℃, and the maximum thermal weight loss temperature increased from 192℃ to 257℃; the thermal decomposition temperature of N-Boc-N'-Boc-L-tryptophan ethyl maltol ester increased from 117℃ to 255℃, and the maximum thermal weight loss temperature increased from 192℃ to 259℃. Therefore, amino acid ethyl maltol ester has a more stable structure, is less prone to oxidation and deterioration, and can release the caramel-sweet aroma compound ethyl maltol during combustion pyrolysis, significantly improving the sensory quality of cigarettes. Attached Figure Description

[0028] Figure 1 Boc-L-phenylalanine maltol ester 1 H NMR spectrum.

[0029] Figure 2 Boc-L-phenylalanine maltol ester 13 C10 NMR spectrum.

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

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

[0032] Figure 5 Boc-L-proline maltol ester 1 H NMR spectrum.

[0033] Figure 6 Boc-L-proline maltol ester 13 C10 NMR spectrum.

[0034] Figure 7 Boc-L-proline ethyl maltol ester 1 H NMR spectrum.

[0035] Figure 8 Boc-L-proline ethyl maltol ester 13 C10 NMR spectrum.

[0036] Figure 9 N-Boc-N'-Boc-L-tryptophan ethyl maltol ester 1 H NMR spectrum.

[0037] Figure 10 N-Boc-N'-Boc-L-tryptophan ethyl maltol ester 13 C10 NMR spectrum.

[0038] Figure 11 The thermogravimetric analysis (TG-DTG) plots of ethyl maltol, Boc-L-phenylalanine ethyl maltol ester, Boc-L-proline ethyl maltol ester and N-Boc-N'-Boc-L-tryptophan ethyl maltol ester are shown, where (a) is the TG curve and (b) is the DTG curve.

[0039] Figure 12 This is the GC spectrum of the thermal decomposition product of Boc-L-phenylalanine maltol ester at 300℃.

[0040] Figure 13 This is the GC spectrum of the thermal decomposition product of Boc-L-phenylalanine ethyl maltol ester at 300℃.

[0041] Figure 14 This is the GC spectrum of the thermal decomposition product of Boc-L-proline maltol ester at 300℃.

[0042] Figure 15 This is the GC spectrum of the thermal decomposition product of Boc-L-proline ethyl maltol ester at 300℃.

[0043] Figure 16 The image shows the GC spectrum of the thermal decomposition product of N-Boc-N'-Boc-L-tryptophan ethyl maltol ester at 300℃. Detailed Implementation

[0044] 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.

[0045] Example 1: Preparation of Boc-L-phenylalanine maltol ester

[0046]

[0047] In a round-bottom flask, Boc-L-phenylalanine (1.2915 g, 6 mmol, 1.2 equiv) and maltol (0.6306 g, 6 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 dichloromethane, and the solvent was removed from the filtrate using a rotary evaporator. The product was separated by column chromatography (DCM:MeOH = 125:1). 1.8583 g of the compound was obtained, with a yield of 83%. 1 HNMR(600MHz,Chloroform-d)δ7.33(d,J=4.4Hz,3H),7.28–7.25(m,2H),6.41(d,J=5.7Hz,1H),4.96(d,J=7.9Hz,1H ),4.74(dt,J=7.8,5.4Hz,1H),3.41(dd,J=14.3,5.5Hz,1H),3.20(dd,J=14.3,7.9Hz,1H),2.24(s,3H),1.39(s,9H); 13 C NMR(151MHz,Chloroform-d)δ176.18,173.83,155.83,154.88,151.07,143.81 ,136.63,130.01,129.04,127.48,113.88,80.54,54.77,38.50,28.85,14.96. HRMS(ESI)m / z[M+H] + Calcd for C 20 H 24 NO6:374.1598; Found:374.1600.

[0048] Example 2: Preparation of Boc-L-phenylalanine ethyl maltol ester

[0049]

[0050] In a round-bottom flask, Boc-L-phenylalanine (2.6513 g, 10 mmol, 1.25 equiv) and ethyl maltol (1.1208 g, 8 mmol, 1 equiv) were added sequentially, followed by dichloromethane (25 mL), then dicyclohexylcarbodiimide (2.0600 g, 10 mmol, 1.25 equiv) and 4-dimethylaminopyridine (0.0400 g, 0.32 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 (DCM:MeOH = 100:1). 2.0133 g of the compound was obtained, with a yield of 65%. 1 H NMR(600MHz,Chloroform-d)δ7.70(d,J=5.7Hz,1H),7.34–7.22(m,5H),6.40(d,J=5.7Hz,1H),5.01(d,J=8.1Hz,1H),4.73(td,J=7.9,5 .5Hz,1H),3.40(dd,J=14.3,5.6Hz,1H),3.19(dd,J=14.3,7.9Hz,1H),2.56(qd,J=7.4,2.8Hz,2H),1.38(s,9H),1.18(t,J=7.6Hz,3H); 13 C NMR(151MHz,Chloroform-d)δ175.52,173.49,155.27,154.82,154.42,142.49,13 6.07,129.44,128.47,126.91,113.19,79.97,54.20,37.94,28.28,21.74,10.77. HRMS(ESI)m / z[M+H] + Calcd forC 21 H 26 NO6:388.1755; Found:388.1756.

[0051] Example 3: Preparation of Boc-L-proline maltol ester

[0052]

[0053] In a round-bottom flask, Boc-L-proline (2.1525 g, 10 mmol, 1.25 equiv) and maltol (1.0089 g, 8 mmol, 1 equiv) were added sequentially, followed by dichloromethane (25 mL), then dicyclohexylcarbodiimide (2.0633 g, 10 mmol, 1.25 equiv) and 4-dimethylaminopyridine (0.04 g, 0.32 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 (DCM:MeOH = 100:1). 1.9905 g of the compound was obtained, with a yield of 77%. 1 H NMR(600MHz,Chloroform-d)δ7.68–7.62(m,1H),6.36(ddd,J=9.2,5.9,2.2Hz,1H),4.57–4.44(m,1H),3.68–3.28(m,2H),2.61–2.40( m,1H),2.39–2.31(m,1H),2.28(dd,J=18.0,2.5Hz,3H),2.22–2.02(m,1H),1.94(ddt,J=12.8,8.8,4.6Hz,1H),1.46(d,J=2.6Hz,9H); 13 C NMR(150MHz,Chloroform-d)δ172.02(171.68),170.06(169.80),159.97(158.88),154.48(153.75),154.20,138. 48(138.23),116.78(116.70),80.18(79.86),58.82,46.74(46.47),31.27(30.28),28.39,24.42(23.37),14.92. HRMS(ESI)m / z[M+H] + Calcd for C 16 H 22 NO6:324.1442; Found:324.1444.

[0054] Example 4: Preparation of Boc-L-proline ethyl maltol ester

[0055]

[0056] In a round-bottom flask, Boc-L-proline (2.1525 g, 10 mmol, 1.25 equiv) and ethyl maltol (1.1208 g, 8 mmol, 1 equiv) were added sequentially, followed by dichloromethane (25 mL), then dicyclohexylcarbodiimide (2.0633 g, 10 mmol, 1.25 equiv) and 4-dimethylaminopyridine (0.05 g, 0.4 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 in the filtrate was removed by rotary evaporation, and the mixture was separated by column chromatography (DCM:MeOH = 100:1). 1.8801 g of the compound was obtained, with a yield of 70%. 1 H NMR(600MHz,Chloroform-d)δ7.66(dd,J=8.4,5.7Hz,1H),6.29(p,J=4.0Hz,1H ),4.43(ddd,J=16.7,8.6,3.5Hz,1H),3.56–3.45(m,1H),3.43–3.30(m,1H),2.6 5–2.49(m,2H),2.49–2.33(m,1H),2.31–2.17(m,1H),2.13–1.96(m,1H),1.86(t t,J=8.0,4.0Hz,1H),1.39(d,J=3.0Hz,9H),1.15(dtd,J=23.0,7.6,2.7Hz,3H); 13 C NMR(150MHz,Chloroform-d)δ178.28,175.79,173.99,154.93,154.89,143.05,113.71,81.4 7(80.70),59.51,47.42(46.86),31.40(29.46),28.94(28.80),24.85(24.20),22.26,11.34. HRMS(ESI)m / z[M+H] + Calcd for C 17 H 24 NO6:338.1601; Found:338.1604.

[0057] Example 5: Preparation of N-Boc-N'-Boc-L-tryptophan ethyl maltol ester

[0058]

[0059] In a round-bottom flask, N-Boc-N'-Boc-L-tryptophan (4.0446 g, 10 mmol, 1.25 equiv) and ethyl maltol (1.1211 g, 8 mmol, 1 equiv) were added sequentially, followed by 25 mL of dichloromethane, then dicyclohexylcarbodiimide (2.0633 g, 10 mmol, 1.25 equiv), and 4-dimethylaminopyridine (0.04 g, 0.32 mmol, 0.04 equiv). Finally, 5 mL of dichloromethane was added, and the mixture was reacted at room temperature for 8 h. After the reaction was complete, the mixture was filtered, and the filter cake was washed with dichloromethane. 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 = 20:1). 1.4734 g of the compound was obtained, with a yield of 35%. 1 HNMR(600MHz,Chloroform-d)δ8.11(s,1H),7.66(d,J=8.4Hz,1H)7.50(d,J=7.7Hz ,1H),7.39(s,1H),7.30(t,J=7.5Hz,1H),7.22(t,J=7.2Hz,1H),6.29(d,J=8.4Hz, 1H)5.13(d,J=7.0Hz,1H),4.62(d,J=5.8Hz,1H),4.14(dd,J=13.7,6.7Hz,2H),3.2 2(ddd,J=45.6,14.5,4.9Hz,2H),1.65(s,9H),1.43(s,9H),1.21(t,J=7.1Hz,3H); 13 C NMR(150MHz,Chloroform-d)δ199.66,198.61,176.72,176.51,155.84,150.21,135.46,133.80,131.24,124.97,124.76,123.09,11 9.59,115.72,85.43,84.16,80.76(80.60),54.04,28.85(28.73),28.38(28.15),25.12(21.71),17.10,14.10(10.29),9.11(9.09). HRMS(ESI)m / z[M+H] + Calcd for C 28 H 35 N2O8:527.2388; Found:527.2383.

[0060] Example 6: Comparison of thermal stability (using amino acid ethyl maltol as an example)

[0061] Depend on Figure 11It is known that ethyl maltol begins to decompose at 117℃, exhibits significant weight loss in the temperature range of 117-205℃, and reaches its maximum weight loss rate at 192℃, with a total weight loss rate of 90.1%. Boc-L-phenylalanine ethyl maltol ester begins to decompose at 154℃, exhibiting significant weight loss in the temperature range of 154-415℃, with the maximum weight loss rate at 226℃, resulting in a total weight loss rate of 98.5%. Boc-L-proline ethyl maltol ester begins to decompose at 212℃, exhibiting significant weight loss in the temperature range of 212-296℃, with the maximum weight loss rate at 257℃, resulting in a total weight loss rate of 93.4%. N-Boc-N'-Boc-L-tryptophan ethyl maltol ester begins to decompose at 177℃, exhibiting significant weight loss in the temperature range of 177-287℃, with the maximum weight loss rate at 255℃, resulting in a total weight loss rate of 91.1%. The data shows that, compared with ethyl maltol, the thermal decomposition temperatures of Boc-L-phenylalanine ethyl maltol ester, Boc-L-proline ethyl maltol ester, and N-Boc-N'-Boc-L-tryptophan ethyl maltol ester increased from 117℃ to 154℃, 212℃, and 255℃, respectively, indicating a significant improvement in thermal stability. Furthermore, the maximum thermal weight loss temperature increased from 192℃ to 226℃, 257℃, and 259℃, respectively.

[0062] Example 7: Pyrolysis products of the target product

[0063] Accurately weigh 2 mg of Boc-L-phenylalanine maltol ester and place it in a pyrolysis apparatus. Rapidly heat to 300 °C at a rate of 20 °C / ms under a helium atmosphere, and analyze the pyrolysis products. Repeat the above procedure with samples of Boc-L-phenylalanine ethyl maltol ester, Boc-L-proline maltol ester, Boc-L-proline ethyl maltol ester, and N-Boc-N'-Boc-L-tryptophan ethyl maltol ester. The total ion chromatogram of the pyrolysis products of the five amino acid phenolic ester compounds is shown below. Figure 12 , Figure 13 , Figure 14 , Figure 15 , Figure 16 The analysis results showed that all five compounds could effectively release maltol or ethyl maltol (marked by arrows in the figure) at 300℃, with a sweet caramel aroma.

[0064] Example 8: Evaluation of the flavoring effect of the target product in tobacco

[0065] The five amino acid phenolic ester latent aroma compounds synthesized in Examples 1-5 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, and after standing for 2 hours, it 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, and then compared with unflavored samples placed under the same conditions. The sensory evaluation results are shown in the table below:

[0066]

[0067]

[0068] 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 scope of protection of the present invention.

Claims

1. An amino acid phenolic ester aroma compound, characterized in that: The structural formula of the amino acid phenolic ester latent fragrance compound is shown in any one of Formulas 1-5: 。 2. The application of the amino acid phenolic ester latent aroma compound of claim 1 in cigarettes.

3. The application according to claim 2, characterized in that: The amino acid phenolic ester latent aroma compound is dissolved in an alcohol or alcohol-water mixture and then evenly 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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