Photoisomerization method of carotenoid
The photoisomerization reaction converts high cis carotenoids into all-trans carotenoids under specific conditions, overcoming the shortcomings of thermal isomerization and chemical catalytic isomerization. This achieves an efficient, controllable, and clean isomerization process suitable for large-scale industrial applications.
Patent Information
- Application Number
- CN202511933145.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-19
- Publication Date
- 2026-02-13
AI Technical Summary
In existing carotenoid synthesis processes, thermal isomerization easily leads to molecular structure destruction, chemical catalytic isomerization has the problem of chemical reagent residues, and photocatalytic isomerization has failed to effectively achieve efficient conversion of all-trans carotenoids.
Under inert gas protection, a photoisomerization reaction is carried out in a photoreactor to photoisomerize high cis carotenoids in a specific wavelength and solvent. The reaction temperature and time are controlled, and the high all-trans carotenoid solid is obtained by post-processing crystallization. The solvent is recycled.
It achieves efficient, controllable, and clean conversion of all-trans carotenoids, with high isomer extraction yield, conforms to the concepts of green chemistry and sustainable development, and is simple to operate.
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of chemical synthesis, and in particular to a photoisomerization method of carotenoids. BACKGROUND
[0002] Carotenoids are a large class of natural pigments, widely exist in the flowers, fruits of plants, and birds, insects, mammals, giving many organisms unique color. So far, more than 700 kinds of carotenoid compounds have been found in nature, of which more than 50 kinds of carotenoids can be used as precursors of VA, which can be converted into VA in vivo. The most important carotenoids are β-carotene, canthaxanthin, astaxanthin, lycopene, lutein, β-apo-8'-carotenoic acid ester, and zeaxanthin, etc. Among them, β-carotene, canthaxanthin, astaxanthin, lycopene and β-apo-8'-carotenoic acid ester have been industrialized.
[0003] Due to the presence of conjugated double bonds, carotenoids are prone to cis-trans isomerization, generating a large number of isomers. For example, β-carotene, in addition to all-trans isomer, also exists 9-cis isomer, 13-cis isomer and 15-cis isomer, etc. There are many factors that affect the geometric isomerization reaction of carotenoids, such as light, solvent, temperature, crystal form, etc.
[0004] The representative process for synthesizing carotenoids at present is C15+10+15 route, which mainly involves Wittig reaction and HWE reaction. The isomer composition of carotenoids synthesized by different reaction types is quite different. All-trans carotenoids have the highest activity, and converting other cis carotenoids into all-trans carotenoids can greatly improve the reaction yield and effectively reduce the product cost, which is of great significance for industrial production.
[0005] Common isomerization methods mainly include thermal isomerization, chemical catalytic isomerization and photo-catalytic isomerization. Thermal isomerization generally needs to be realized at a high temperature. Carotenoids are heat-sensitive substances, and their molecular structure will be destroyed at a high temperature for a long time, resulting in deterioration. Chemical catalytic isomerization breaks the original chemical bond through the interaction of specific chemical reagents and substrates, and rearranges to form more stable isomers. Common chemical reagents include acids, bases and metal catalysts. Chemical catalytic isomerization has the advantages of high selectivity and mild conditions, but the chemical reagents used may be left in the product, which is difficult to separate completely, affecting the purification of isomerization products, and cannot be reused.
[0006] Compared with thermal isomerization and chemical catalytic isomerization, photocatalytic isomerization does not require harsh conditions such as high temperature and high pressure, can be driven at room temperature by specific wavelength light, has high selectivity and controllability, does not need to rely on chemical reagents, and has no chemical reagent residues and separation and purification problems. In addition, light energy belongs to renewable energy, which meets the green chemistry and sustainable development concept. SUMMARY
[0007] In order to overcome the shortcomings of the prior art, the present application provides a method for extracting all-trans carotenoids by high-cis carotenoid photoisomerization. The method can efficiently isomerize various cis carotenoids to all-trans carotenoids while inhibiting the conversion of all-trans carotenoids to cis carotenoids. The isomerization method has the characteristics of mild conditions, high efficiency, controllability, cleanliness, etc., meets the green chemistry and sustainable development concept, and is simple to operate, has high extraction yield, and is suitable for large-scale production.
[0008] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:
[0009] A photoisomerization method of carotenoids, comprising,
[0010] Under the protection of inert gas, high-cis carotenoids to be isomerized and an organic solvent are added to a photo reactor, and photoisomerization reaction is carried out under light irradiation. After the reaction is completed, high all-trans carotenoids are obtained by post-treatment.
[0011] Preferably, the high-cis carotenoids to be isomerized are a mixture of one or more of 7-cis, 9-cis, 11-cis, 13-cis, 15-cis, 13'-cis, 9,13-dicis, 9,15-dicis, 13,15-dicis and 9,13'-dicis isomers.
[0012] The carotenoids are selected from at least one of beta-apo-8'-carotenyl acid ethyl ester, beta-carotene, canthaxanthin, astaxanthin and lycopene.
[0013] Preferably, the content of all-trans carotenoids to be isomerized is between 10% and 60%, and the content is between 20% and 70%.
[0014] Preferably, the photo reactor is one of top-illumination, inner-illumination or bottom-illumination, preferably top-illumination; the light wavelength is between 430 nm and 470 nm, preferably 440 nm to 460 nm; the light source is a high-pressure mercury lamp or an LED lamp, preferably an LED lamp; the lamp power is 5-50 W, preferably 10-20 W. The wavelength and power have a key influence on the isomerization reaction.
[0015] Preferably, the photoisomerization is carried out in an organic solvent, which is a C2-C8 alkane solvent, preferably petroleum ether, n-heptane or cyclohexane; at least one of C1-C4 alcohol solvents, preferably one or a combination of methanol and ethanol, and the type of solvent has a great influence on the efficiency of photoisomerization.
[0016] The amount of the organic solvent is 1-10 mL, based on 1 g of the high-cis carotenoid to be isomerized.
[0017] Preferably, the temperature of the photoisomerization reaction is 10-40°C, preferably 20-35°C; and the time of the photoisomerization reaction is 3-60 h, preferably 6-25 h.
[0018] Preferably, the inert gas is nitrogen, and the photoisomerization is carried out under nitrogen protection.
[0019] Preferably, the specific operation of the post-treatment is as follows:
[0020] Step 1): After isomerization to a certain extent, the isomerization system is first cooled to 0-30°C under nitrogen protection, and water is added to form an aqueous system or no water is added, and the complete crystallization of all-trans carotenoids in the system is waited for.
[0021] Step 2): After the complete crystallization, filtration is carried out, the filter cake is stirred with the same solvent as the isomerization system once, and is dried to obtain high all-trans carotenoid solid.
[0022] Preferably, the isomerization to a certain extent in step 2) means that the HPLC monitoring shows no significant increase in the proportion of all-trans isomers; and the high all-trans carotenoid obtained has a proportion of all-trans ≥ 85%.
[0023] Preferably, the mother liquor after extraction and filtration in step 2) can be combined in multiple batches to repeat the above isomerization operation, or can be directly used for the next batch of photoisomerization.
[0024] The present application has the following advantages:
[0025] 1. The photoisomerization method of carotenoids of the present application, wherein the cis carotenoids are dispersed in an alkane or alcohol solvent and subjected to photoisomerization in a photoisomerization reactor, and the isomerization is carried out to a certain extent until the HPLC monitoring shows no significant increase in the proportion of all-trans isomers, and then the temperature is cooled to 0-30°C, and the complete crystallization of all-trans carotenoids is waited for, and then filtration is carried out to obtain carotenoid solid with a proportion of all-trans ≥ 85%, and the filtrate is subjected to photoisomerization extraction or is directly used for the next batch as a photoisomerization solvent. The isomerization of this method has the characteristics of high efficiency, controllability and cleanliness, and conforms to the concepts of green chemistry and sustainable development, and the isomerization extraction operation is simple and the extraction yield is high.
[0026] 2. The reaction raw materials used in this invention, such as alkanes and alcohols, are all bulk industrial products. The raw materials are readily available, low in cost, and of great industrial value.
[0027] 3. This invention does not use highly hazardous raw materials in the isomerization process of cis-carotenoids, and there are no other harmful byproduct residues in the product. The production process is highly safe, and the product meets the usage standards. Detailed Implementation
[0028] The present invention will be further described below with reference to specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments.
[0029] The reagent sources in the various embodiments of this invention are as follows:
[0030] Petroleum ether: Industrial grade;
[0031] n-Heptane: ≥99%, industrial grade;
[0032] Methanol: ≥99%, industrial grade;
[0033] Ethanol: ≥99%, industrial grade.
[0034] The analytical instruments involved in the following embodiments of the present invention are as follows:
[0035] Liquid chromatography: High performance liquid chromatograph, Shimadzu SPD-M20A.
[0036] Example 1:
[0037] The isomerization reaction is carried out according to the following steps:
[0038] First light exposure: Under nitrogen protection, add 38.13g of [amount of substance] to the upward-illuminated photoreactor. β-Apo-8'-carotene ethyl ester (HPLC purity 27.03%, all-trans fraction 15.45%, equivalent to 10.31 g of pure product) was dispersed in 114 ml of n-heptane solution and photoisomerized at 30-35°C using a 15W LED lamp with a wavelength between 450 and 460 nm. The isomerization process was monitored by HPLC until the all-trans fraction reached 34.83%. The photoisomerization took 5 hours. After isomerization, the temperature was lowered to about 30°C, filtered, and washed with about 20 ml of n-heptane. The product was then dried under vacuum to obtain 5.13 g of dried β-Apo-8'-carotene ethyl ester with an HPLC purity of 79.79%, equivalent to 4.09 g of pure product, an all-trans fraction of 85.03%, and an isomerization extraction yield of 39.67% (extraction yield = pure product obtained / pure product input * 100%, the same below). The filtrate was concentrated with approximately 40 ml of n-heptane and then used for secondary light exposure.
[0039] Secondary Irradiation: Under nitrogen protection, the concentrate of the filtrate from the first irradiation was added to an upward-illuminated photoreactor. Photoisomerization was performed using a 15W LED lamp with a wavelength between 450 and 460 nm at 30-35°C. The isomerization process was monitored by HPLC until the all-trans fraction reached 32.43%. The photoisomerization process took 5 hours. After isomerization, the temperature was lowered to approximately 30°C, filtered, and the residue was transferred and washed with approximately 20 ml of n-heptane. The residue was then dried under vacuum to obtain 4.40 g of dried β-apo-8'-carotene ethyl ester, with an HPLC purity of 76.38%, 3.36 g of pure product, an all-trans fraction of 83.72%, and an isomerization yield of 32.59%. The filtrate was concentrated with approximately 30 ml of n-heptane and then used for a third irradiation.
[0040] Three-stage light irradiation: Under nitrogen protection, the concentrate from the second-stage light irradiation was added to an upward-illuminated photo-isomerizing reactor. Photoisomerization was performed using a 15W LED lamp with a wavelength between 450 and 460 nm at 30-35°C. HPLC was used to monitor the isomerization process until the all-trans fraction reached 29.37%. The photoisomerization process took 5 hours. After isomerization, the temperature was lowered to approximately 30°C, filtered, and the mixture was washed with approximately 20 ml of n-heptane. The mixture was then dried under vacuum to obtain 2.77 g of dried β-apo-8'-carotene ethyl ester, with an HPLC purity of 72.14%. 2.00 g of the pure product was obtained, with an all-trans fraction of 81.42% and an isomerization yield of 19.40%. The total yield of the three-stage light-irradiation isomerization extraction was 89.74%.
[0041] Example 2:
[0042] The isomerization reaction is carried out according to the following steps:
[0043] Under nitrogen protection, 42.92 g of ethyl β-apo-8'-carotene (HPLC purity 50.73%, all-trans fraction 65.00%, pure product 21.77 g) was added to an upward-illuminated photoreactor and dispersed in 186 ml of n-heptane solution. Photoisomerization was performed using a 20 W LED lamp with a wavelength between 440 and 450 nm at 35-40 °C. The isomerization process was monitored by HPLC until the all-trans fraction reached 84.75%. The photoisomerization took 12 hours. After isomerization, the temperature was lowered to about 25 °C, filtered, and washed with about 30 ml of n-heptane. The product was then dried under vacuum to obtain 22.50 g of dried ethyl β-apo-8'-carotene, with an HPLC purity of 85.83%, 19.31 g of pure product, an all-trans fraction of 85.28%, and an isomerization yield of 88.70%.
[0044] The mother liquor is used as the photoisomerization solvent for the next batch.
[0045] Example 3:
[0046] The isomerization reaction is carried out according to the following steps:
[0047] Under nitrogen protection, 10.38 g of β-carotene (UV content 50.17%, all-trans percentage 53.21%, pure product 5.21 g) was added to an upward-illuminated photoreactor and dispersed in 100 ml of anhydrous ethanol solution. Photoisomerization was performed using a 15 W LED lamp with a wavelength between 450 and 460 nm at 30-35 °C. The isomerization process was monitored by HPLC until the all-trans percentage reached 82.45%. The photoisomerization took 24 h. After isomerization, the temperature was lowered to about 30 °C, filtered, and washed with about 30 ml of ethanol. The product was then dried under vacuum to obtain 5.47 g of dried β-carotene with a UV content of 85.46%, 4.67 g of pure product, and an all-trans percentage of 85.63%. The isomerization extraction yield was 89.64%.
[0048] The mother liquor is used as the photoisomerization solvent for the next batch.
[0049] Example 4:
[0050] The isomerization reaction is carried out according to the following steps:
[0051] Under nitrogen protection, 9.32 g of β-carotene (UV content 45.78%, all-trans percentage 56.27%, pure product 4.27 g) was added to an upward-illuminated photocatalytic reactor and dispersed in 75 ml of anhydrous mixed alcohol solution (methanol=55%, ethanol=45%). Photoisomerization was performed using a 15W LED lamp with a wavelength between 440 and 450 nm at 25-30 °C. The isomerization process was monitored by HPLC until the all-trans percentage reached 81.82%. The photoisomerization took 15 h. After isomerization, the temperature was lowered to about 25 °C, filtered, and washed with about 30 ml of mixed alcohol. The product was then dried under vacuum to obtain 4.43 g of dried β-carotene with a UV content of 84.96%, 3.76 g of pure product, an all-trans percentage of 86.03%, and an isomerization yield of 88.06%.
[0052] The mother liquor is used as the photoisomerization solvent for the next batch.
[0053] Comparative Example 1:
[0054] The isomerization reaction is carried out according to the following steps:
[0055] Under nitrogen protection, 9.00 g of β-carotene (UV content 35.76%, all-trans fraction 29.49%, pure product 3.22 g) was added to an upward-illuminated photocatalytic reactor and dispersed in 75 ml of anhydrous mixed alcohol solution (methanol=55%, ethanol=45%). Photoisomerization was performed using a 15W LED lamp with a wavelength between 350 and 360 nm at 25-30°C. The isomerization process was monitored by HPLC until the all-trans fraction was only 29.54%. The photoisomerization took 22 hours. After isomerization, the temperature was lowered to about 25°C, filtered, and washed with about 30 ml of mixed alcohol. The product was then dried under vacuum to obtain 4.30 g of dried β-carotene with a UV content of 38.46%, 1.65 g of pure product, and an all-trans fraction of 31.29%. The isomerization extraction yield was 51.24%.
[0056] The mother liquor is used as the photoisomerization solvent for the next batch.
[0057] The results of Comparative Example 1 show that, with other conditions unchanged, the change in wavelength resulted in a lower proportion of all-trans morphology of the product and a significant decrease in the isomer extraction yield.
[0058] Comparative Example 2:
[0059] The isomerization reaction is carried out according to the following steps:
[0060] Under nitrogen protection, 9.00 g of β-carotene (UV content 53.75%, all-trans fraction 36.48%, pure product 4.84 g) was added to an upward-illuminated photocatalytic reactor and dispersed in 75 ml of anhydrous mixed alcohol solution (methanol=55%, ethanol=45%). Photoisomerization was performed using a 2W LED lamp with a wavelength between 440 and 450 nm at 25-30 °C. The isomerization process was monitored by HPLC until the all-trans fraction reached 38.63%. The photoisomerization took 22 h. After isomerization, the temperature was lowered to about 25 °C, filtered, and washed with about 30 ml of mixed alcohol. The product was then dried under vacuum to obtain 4.49 g of dried β-carotene with a UV content of 55.94%, 2.51 g of pure product, an all-trans fraction of 40.57%, and an isomerization yield of 51.86%.
[0061] The mother liquor is used as the photoisomerization solvent for the next batch.
[0062] The results of Comparative Examples 1 and 2 show that, with other conditions remaining constant, the proportion of all-trans morphology of the product is lower and the isomer extraction yield is lower after changing the wavelength or power. In particular, the isomer extraction yield is significantly reduced after changing the wavelength.
[0063] Comparative Example 3:
[0064] The isomerization reaction is carried out according to the following steps:
[0065] Under nitrogen protection, 30.00 g of ethyl β-apo-8'-carotene (HPLC purity 48.02%, all-trans fraction 57.83%, pure product 14.41 g) was added to an upward-illuminated photoreactor and dispersed in 135 ml of ethyl acetate solution. Photoisomerization was performed using a 15 W LED lamp with a wavelength between 440 and 450 nm at 35-40 °C. The isomerization process was monitored by HPLC until the all-trans fraction reached 58.32%. The photoisomerization took 13 hours. After isomerization, the temperature was lowered to about 25 °C, filtered, and washed with about 30 ml of ethyl acetate. The product was then dried under vacuum to obtain 12.96 g of dried ethyl β-apo-8'-carotene, with an HPLC purity of 50.36%, 6.53 g of pure product, an all-trans fraction of 60.33%, and an isomerization yield of 45.32%.
[0066] The results of Comparative Example 3 show that, with other conditions unchanged, the proportion of all-trans morphology of the product decreased and the isomer extraction yield also decreased after the solvent was changed.
[0067] The mother liquor is used as the photoisomerization solvent for the next batch.
[0068] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.
Claims
1. A method for photoisomerization of carotenoids, characterized in that, The method comprises the following steps: The high-cis carotenoid to be isomerized and an organic solvent are added into a photo reactor under the protection of inert gas, and photoisomerization is carried out under light irradiation; after the reaction is completed, the high-all-trans carotenoid solid is obtained through post-treatment.
2. The photoisomerization method of carotenoids according to claim 1, characterized in that, The high-cis carotenoid to be isomerized is a mixture of one or more of 7-cis, 9-cis, 11-cis, 13-cis, 15-cis, 13'-cis, 9,13-dicis, 9,15-dicis, 13,15-dicis and 9,13'-dicis isomers; The carotenoid is at least one of β-apo-8'-carotenoic acid ethyl ester, β-carotene, canthaxanthin, astaxanthin and lycopene.
3. The photoisomerization method of carotenoids according to claim 1 or 2, characterized in that, The content of all-trans carotenoid in the high-cis carotenoid to be isomerized is between 10% and 60%.
4. The photoisomerization method of carotenoids according to claim 1, characterized in that, The photo reactor is one of an upper-illumination type, an inner-illumination type or a lower-illumination type. The wavelength of the light irradiation is between 430 nm and 470 nm. The light source for the light irradiation is a high-pressure mercury lamp or an LED lamp, and the lamp power is between 5 W and 50 W.
5. The photoisomerization method of carotenoids according to claim 1, characterized in that, The photoisomerization is carried out in an organic solvent, and the organic solvent is at least one of a C5-C8 alkane solvent and a C1-C4 alcohol solvent. The amount of the organic solvent is between 1 mL and 10 mL per 1 g of the high-cis carotenoid to be isomerized.
6. The photoisomerization method of carotenoids according to claim 1, characterized in that, The temperature of the photoisomerization is between 10°C and 40°C, and the time of the photoisomerization is between 3 h and 60 h.
7. The photoisomerization method of carotenoids according to claim 1, characterized in that, The inert gas is nitrogen, and the whole process of the photoisomerization is carried out under the protection of nitrogen.
8. The photoisomerization method of carotenoids according to claim 1, characterized in that, The specific operation of the post-treatment is as follows: Step 1): after isomerization to a certain extent, the isomerization system is cooled to between 0°C and 30°C under the protection of nitrogen, and water is added to form an aqueous system or no water is added, and the all-trans carotenoid in the system is completely crystallized; Step 2): after the crystallization is completed, filtration is carried out, the filter cake is stirred with the same organic solvent as the isomerization system once, is dried by suction, and is dried to obtain the high-all-trans carotenoid solid.
9. The photoisomerization method of carotenoids according to claim 8, characterized in that, The isomerization to a certain extent refers to that the proportion of the all-trans isomer does not increase obviously under HPLC monitoring.
10. The photoisomerization method of carotenoids according to claim 8, characterized in that, The mother liquor after filtration is combined in multiple batches to repeat the isomerization operation, or is directly used for the isomerization of the next batch.