CN108558621B - Citral di-bornyl acetal derivative and preparation method and application thereof - Google Patents
Citral di-bornyl acetal derivative and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a citral di-bornyl acetal derivative, a preparation method and application thereof. The structural formula of the citral di-bornyl acetal derivative is shown as a formula I. According to the invention, citral dimethyl acetal and borneol are subjected to distillation reaction under the action of a catalyst to obtain the citral di-bornyl acetal derivative. The citral-di-bornyl acetal derivative is stable, and the antibacterial performance of the citral-di-bornyl acetal derivative is far superior to that of borneol and citral; the acid-sensitive micromolecule drug also has the acid-sensitive characteristic, so the invention has a certain medicinal function of controlling release at the same time, and can be applied to the preparation of acid-sensitive micromolecule drug monomers. The raw materials and reagents used in the invention are simple and easily available, the reaction conditions are mild, the difficulty of the operation method is not high, and the product has wide application prospects in the fields of organic chemistry and medicines.
Description
Technical Field
The invention belongs to the field of organic chemistry, and particularly relates to a citral di-bornyl acetal derivative, and a preparation method and application thereof.
Background
Borneol, also known as Borneolum Syntheticum and borneol, is a bicyclic monoterpene alcohol. The borneol is divided into natural borneol and synthetic borneol, the borneol has pharmacological activities of anti-inflammation, sterilization, analgesia, antioxidation and the like, but when the borneol is used as a single medicine, the borneol has the defects of low efficacy, strong volatility, poor solubility and the like.
How to further reform the borneol, overcome the defects of the borneol and play the advantages of the borneol so as to ensure that the application range of the borneol is wider, which is a problem to be solved.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a citral di-bornyl acetal derivative.
Another object of the present invention is to provide a process for producing the above-mentioned citral norbornyl acetal derivative.
It is still another object of the present invention to provide use of the above-mentioned citral norbornyl acetal derivative.
The purpose of the invention is realized by the following technical scheme: a citral di-bornyl acetal derivative has a structural formula shown in formula I:
the preparation method of the citral di-bornyl acetal derivative comprises the following steps: carrying out distillation reaction on citral dimethyl acetal and borneol under the action of a catalyst I to obtain a citral di-bornyl acetal derivative; more preferably, the method comprises the following steps:
(1) dissolving citral dimethyl acetal, borneol and a catalyst I in an organic solvent I, carrying out distillation reaction under a stirring state, tracking the reaction process by using thin-layer chromatography, and continuously supplementing the organic solvent I lost by distillation;
(2) adding saturated sodium bicarbonate until the pH value of the system is 7-8, filtering to remove insoluble substances, separating the liquid, collecting an organic layer, and removing water;
(3) filtering, removing solvent under reduced pressure, separating by column chromatography, eluting with petroleum ether and ethyl acetate at volume ratio of 6:1 to obtain yellowish liquid as citral-di-bornyl acetal derivative.
The citral dimethyl acetal and the borneol in the step (1) are preferably mixed according to the molar ratio of 1: 2-2.5; more preferably, the molar ratio is 1: 2-2.1.
The organic solvent I in the step (1) is preferably one or two of chloroform and toluene; more preferably chloroform.
The dosage of the organic solvent I in the step (1) is based on the condition that all reaction substances can be fully dissolved; preferably, the proportion of the organic solvent I is 2.5-3 mL per gram of the reaction substances (namely, the citral dimethyl acetal and the borneol).
The catalyst I in the step (1) is preferably p-toluenesulfonic acid.
The dosage of the catalyst in the step (1) is the catalytic dosage; the mass usage amount is preferably 0.2-0.8% of the mass of the citral; more preferably 0.3 to 0.4% by mass of citral.
The stirring speed in the step (1) is preferably 800-1400 r/min.
The distillation reaction in the step (1) is preferably carried out at 62-68 ℃ for 4-12 hours.
The water removal in the step (2) is preferably performed by using anhydrous sodium sulfate.
The water removal described in step (2) is preferably carried out by: anhydrous sodium sulfate, the mass of which is 1-3 times that of citral dimethyl acetal, is used for removing water for 4-8 hours.
Silica gel with the specification of 100-400 meshes is preferably selected as the filler for the column chromatography in the step (3); more preferably, the specification is 300-400 mesh silica gel.
The column chromatography separation described in step (3) preferably comprises the following steps: and (3) sampling, eluting impurities by using a solution of petroleum ether and ethyl acetate according to the volume ratio of more than 6:1, and then eluting by using a solution of petroleum ether and ethyl acetate according to the volume ratio of 6:1 to obtain a product of a light yellow liquid, namely the citral di-boryl acetal derivative.
The solution of petroleum ether and ethyl acetate in a volume ratio of more than 6:1 is a solution prepared by mixing petroleum ether and ethyl acetate in a volume ratio of 8-10: 1.
The catalyst I is preferably p-toluenesulfonic acid.
The distillation reaction is preferably carried out at 62-68 ℃ for 4-12 hours.
The citral dimethyl acetal can be obtained commercially or prepared by a method comprising the following steps:
1) dissolving citral and trimethyl orthoformate in an organic solvent A, adding a catalyst A, and carrying out reflux reaction at 60-90 ℃ under a stirring state to obtain a reaction system A;
2) adding a saturated sodium bicarbonate aqueous solution into the reaction system A until the pH value is 7-8 to remove the p-toluenesulfonic acid, and concentrating under reduced pressure; then extracting with an organic solvent B, collecting an organic layer, and further removing water;
3) filtering, removing solvent under reduced pressure, separating by column chromatography, and eluting with petroleum ether and ethyl acetate at volume ratio of 10:1 to obtain light yellow liquid (citral dimethyl acetal).
The trimethyl orthoformate in the step 1) is used in an excessive amount, and the molar amount of the trimethyl orthoformate is preferably 3-4 times of the molar amount of the citral.
The organic solvent A in the step 1) is preferably alcohol; more preferably alcohols with carbon chain lengths of C1-C3; most preferred is methanol.
The dosage of the organic solvent A in the step 1) is based on the condition that all reaction substances can be fully dissolved; preferably, the organic solvent A is prepared in a ratio of 1.5-2 mL per gram of the reaction substances (i.e. citral and trimethyl orthoformate).
The catalyst described in step 1) is preferably p-toluenesulfonic acid.
The dosage of the catalyst in the step 1) is the catalytic dosage; the mass usage amount is preferably 0.2-0.8% of the mass of the citral; more preferably 0.3 to 0.4% by mass of citral.
The rotating speed of stirring in the step 1) is preferably 800-1400 r/min.
The temperature of the reflux reaction in the step 1) is preferably 68-80 ℃.
The time of the reflux reaction in the step 1) is preferably 4-8 hours.
The saturated aqueous sodium bicarbonate solution described in step 2) is preferably added in portions.
The organic solvent B in the step 2) is preferably one or at least two of dichloromethane and chloroform.
The number of extractions described in step 2) is preferably at least 3.
The water removal in step 2) is preferably performed by using anhydrous sodium sulfate.
The water removal described in step 2) is preferably carried out by: and (3) dehydrating for 4-8 hours by using anhydrous sodium sulfate with the mass 1-3 times that of the citral.
Silica gel with the specification of 100-400 meshes is preferably selected as the filler for the column chromatography in the step 3); more preferably, the specification is 300-400 mesh silica gel.
The column chromatography separation described in step 3) preferably comprises the following steps: and (3) sampling, eluting impurities by using a solution of petroleum ether and ethyl acetate according to the volume ratio of more than 10:1, and then eluting by using a solution of petroleum ether and ethyl acetate according to the volume ratio of 10:1 to obtain a product of a light yellow liquid, namely the citral di-boryl acetal derivative.
The solution of petroleum ether and ethyl acetate in a volume ratio of more than 10:1 is a solution prepared from petroleum ether and ethyl acetate in a volume ratio of 15-20: 1.
The application of the citral-norbornyl acetal derivative in preparing acid-sensitive small-molecule drug monomers.
Compared with the prior art, the invention has the following advantages and effects:
(1) the raw materials and reagents used in the invention are simple and easily available, the reaction conditions are mild, the difficulty of the operation method is not high, and the product has wide application prospects in the fields of organic chemistry and medicines.
(2) The invention also has acid-sensitive properties. The sensitivity refers to that under the weak acid or medium strong acid condition, acetal bond is broken to generate corresponding aldehyde and alcohol, and the citral has medicinal value, so the invention has a certain medicinal function of controlled release. The degradation process is shown as the following reaction formula:
(3) the citral-di-bornyl acetal derivative provided by the invention is stable, and the antibacterial performance of the citral-di-bornyl acetal derivative is far superior to that of borneol and citral.
Drawings
FIG. 1 is a reaction equation of example 1 of the present invention.
FIG. 2 is a NMR spectrum of the product of example 1 of the present invention.
FIG. 3 is an infrared spectrum of the product of example 1 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
Example 1
The preparation of a derivative of citral-bisboryl acetal, as shown in FIG. 1, comprises the following steps:
(1) weighing 7.6120g (0.05mol, molecular weight 152.23) of citral and 21.2240g (0.20mol, molecular weight 106.12) of trimethyl orthoformate in a dry and clean round-bottom flask at room temperature, dissolving in 50mL of methanol, adding 28.56mg of p-toluenesulfonic acid, and carrying out reflux reaction on a reaction system at 80 ℃ and 800r/min for 6 hours;
(2) adding saturated aqueous sodium bicarbonate solution to the reaction system in batches until the pH value is 7-8, removing p-toluenesulfonic acid, concentrating under reduced pressure, extracting with 30mL of dichloromethane for 3 times, collecting an organic layer, adding 9.4522g of anhydrous sodium sulfate, and removing water for 6 hours;
(3) the anhydrous sodium sulfate was removed by filtration, the solvent was removed under reduced pressure, and analysis was carried out using a silica gel column having an average particle size of 48 μm: firstly, dissolving silica gel in petroleum ether, stirring uniformly by using a glass rod to make the solution be thick, pouring the thick solution into a chromatographic column (2cm multiplied by 20cm, the same below), compacting the column by using a low-pressure pump, beating the silica gel column by using an aurilave, and discharging bubbles in the column as far as possible; after the silica gel column is filled, slowly pouring the sample into the silica gel column, lightly beating the column by using an aurilave to uniformly distribute the sample, and then washing by using an eluant; if the sample is not scattered, 1-2 g of quartz sand can be added to cover the sample after the sample is poured. After the sample is loaded, 50mL of eluant with a slightly larger proportion (petroleum ether: ethyl acetate: 12: 1 in volume ratio) is used for washing, impurities with small polarity are washed out, and then 50mL of solution obtained by mixing petroleum ether and ethyl acetate according to the volume ratio of 10:1 is used for eluting, so that 8.1482g of citral dimethyl acetal serving as a light yellow liquid is obtained, and the yield is 82%.
(4) 8.1482g (0.041mol, molecular weight 198.3) of citral dimethyl acetal obtained in step (3) and 13.7028g (0.09mol, molecular weight 154.25) of natural borneol are dissolved in 60mL of chloroform, 23.62mg of p-toluenesulfonic acid is added, the mixture is distilled and reacted for 8 hours at 68 ℃ and a stirring speed of 1000r/min, and the reaction progress is tracked by using thin layer chromatography (the reaction product has no raw material point and the target product point becomes dark in color, so that the reaction is determined to be finished). A two-necked round-bottomed flask was used as a vessel, and the chloroform lost by distillation was continuously replenished.
(5) Adding saturated sodium bicarbonate to the reaction system in the step (4) in batches until the pH value of the system is 7-8, filtering to remove insoluble substances, separating an organic layer and a water layer, and collecting the organic layer; mixing chloroform with the water layer obtained by the previous liquid separation, separating liquid, and collecting an organic layer; the resulting organic layers were combined, and 8.3421g of anhydrous sodium sulfate was added to remove water for 4 hours.
(6) The anhydrous sodium sulfate was removed by filtration, the solvent was removed under reduced pressure and analyzed using a silica gel column having an average particle size of 48 μm, after loading, the column was washed with 50mL of an eluent having a slightly larger ratio (petroleum ether: ethyl acetate: 8: 1 by volume), to elute impurities having a small polarity, and then eluted with 50mL of a solution obtained by mixing petroleum ether and ethyl acetate at a volume ratio of 6:1 to obtain 4.6860g of a product as a pale yellow liquid, with a yield of 26%.
The citral-bis-bornyl acetal derivative obtained in example 1 was tested:
(A) the nuclear magnetic resonance image is shown in FIG. 2: 1H NMR (500MHz, CDCl3) δ 7.49(s,17H),7.34(t, J ═ 18.6Hz,7H), 7.49-7.08 (m,29H), 7.49-6.94 (m,30H), 7.49-6.70 (m,33H), 7.49-6.04 (m,46H), 7.49-6.01 (m,47H), 7.49-5.97 (m,48H), 7.49-5.91 (m,49H), 7.49-5.86 (m,50H), 7.49-5.74 (m,54H), 7.49-5.58 (m,60H), 7.49-5.27 (m,70H), 7.49-5.18 (m,72H), 7.49-5.01 (m,78H),5.03(s,6H), 7.49-5.27 (m,70H), 7.49-5.18 (m,72H), 7.49-5.3.14H, 3.14H, 3.3.14H, 3.12H, 3.14H, 3.12H, 3.12, 3, 3.12H, 3H, 12, 3H, j ═ 32.5,21.7,9.3Hz,34H),1.82(s,5H), 1.82-1.36 (m,150H), 1.36-1.17 (m,292H),1.10(ddd, J ═ 23.0,14.9,9.1Hz,55H), 1.05-0.81 (m,452H),0.79(dd, J ═ 14.9,7.9Hz,46H),0.04(d, J ═ 35.4Hz, 21H).
(B) The infrared spectrogram is shown in FIG. 3: absorption wavelength of 1690, 1655cm-1Determining the medium-strong absorption peak as a carbon-carbon double bond; the absorption wavelength is 1255cm-1The medium-strong absorption peak at the position was judged as the C-O-C ether structure.
Fig. 2 and 3 simultaneously demonstrate the successful synthesis of the citral-bis-bornyl acetal derivative, of the formula:
example 2
(1) 3.8221g (0.025mol) of citral and 10.3421g (0.097mol) of trimethyl orthoformate were weighed out at room temperature into a dry, clean round-bottom flask, dissolved in 40mL of methanol, and 15.21mg of p-toluenesulfonic acid was added and the reaction was refluxed at 75 ℃ and 800r/min for 4 hours.
(2) To the reaction system, a saturated aqueous sodium bicarbonate solution was added in portions to pH 7 to 8, p-toluenesulfonic acid was removed, concentrated under reduced pressure, extracted 3 times with 30mL of dichloromethane, the organic layer was collected, and 5.3214g of anhydrous sodium sulfate was added to remove water for 4 hours.
(3) The anhydrous sodium sulfate was removed by filtration, the solvent was removed under reduced pressure, the column was analyzed using a silica gel column with an average particle size of 37 μm, after loading, the column was washed with 50mL of a slightly larger eluent (15: 1 by volume) to elute impurities with low polarity, and then the column was eluted with a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 10:1 to obtain 3.3487g of citral and dimethoxyacetal as pale yellow liquids with a yield of 68%.
(4) 3.3487g and 4.8856g of citral dimethoxy acetal obtained in step (3) were dissolved in 40mL of chloroform, 12.34mg of p-toluenesulfonic acid was added, and the reaction was distilled at 68 ℃ and a stirring speed of 1000r/min for 4 hours, and the progress of the reaction was followed by thin layer chromatography. A two-necked round-bottomed flask was used as a vessel, and the chloroform lost by distillation was continuously replenished.
(5) Adding saturated sodium bicarbonate to the reaction system in the step (4) in batches until the pH value of the system is 7-8, filtering to remove insoluble substances, separating an organic layer and a water layer, and collecting the organic layer; mixing chloroform with the water layer obtained by the previous liquid separation, separating liquid, and collecting an organic layer; the resulting organic layers were combined, and 5.215g of anhydrous sodium sulfate was added to remove water for 4 hours.
(6) The anhydrous sodium sulfate was removed by filtration, the solvent was removed under reduced pressure and analyzed using a silica gel column having an average particle size of 37 μm, after loading, the column was washed with 50mL of an eluent having a slightly larger ratio (petroleum ether: ethyl acetate: 10:1 by volume), to elute impurities having a small polarity, and the product was eluted with a solution obtained by mixing petroleum ether and ethyl acetate at a volume ratio of 6:1 to obtain 2.4578g of the citral dimethoxyacetal borneol derivative as a pale yellow liquid, with a yield of 33%.
Examples of the applications
Weighing the citral dimethoxy acetal borneol derivatives obtained in the example 1 and the example 2, respectively drying at 50 ℃ for 8h in vacuum, respectively dissolving 1g of each derivative in 10mL of ethanol solution, diluting with 90mL of sterile physiological saline, and uniformly stirring to prepare a drug test solution. Separately, borneol and citral solutions with the same concentration (the same mass concentration, 10mg/mL) were prepared as controls. The sterilized LB agar medium was heated to melt, and when cooled to 40 ℃, the LB agar medium was poured into a sterile petri dish. After the flat plate is naturally dried, transferring a test solution and a test bacterial suspension of a drug to be tested respectively, uniformly coating the test solution and the test bacterial suspension on the flat plate, repeating each treatment for 3 times, and inverting after coating (coating 100 mu L of test bacterial solution and then coating 10 mu L of the test solution of the drug to be tested); the test bacteria are respectively escherichia coli standard strain ATCC25922, staphylococcus aureus standard strain ATCC25923, pseudomonas aeruginosa standard strain ATCC27853 and listeria monocytogenes standard strain ATCC19115 (Kyoto Loop-Kai Microscience Co., Ltd.). A control group is additionally arranged, bacteria are smeared, and the liquid medicine is replaced by the same amount of sterile physiological saline. And culturing the prepared bacterial plate at the constant temperature of 37 ℃ for 24h, and counting the number of colonies. The formula for calculating the bacteriostasis rate is as follows:
bacteriostatic rate (number of control colonies-number of liquid medicine treatment colonies)/number of control colonies
TABLE 1
The inhibition rates in table 1 are the average of the obtained inhibition rates of three parallel experiments.
As can be seen from table 1, the citral dimethoxyacetal borneol derivative provided by the invention has a significant inhibitory effect on escherichia coli, staphylococcus aureus and other bacteria. Compared with borneol and citral, the citral dimethoxyacetal borneol derivative has better antibacterial effect, wherein the antibacterial effect on pseudomonas aeruginosa is the best, and the antibacterial rate can reach 99.2% at most, which shows that the prepared borneol derivative has better biological activity than borneol and citral and has very excellent potential value in the fields of medicine and chemistry.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A citral di-bornyl acetal derivative, characterized by a structural formula shown in formula I:
(formula I).
2. A process for the preparation of a citral norbornyl acetal derivative according to claim 1, characterized by comprising the steps of: carrying out distillation reaction on citral dimethyl acetal and borneol under the action of a catalyst I to obtain a citral di-bornyl acetal derivative;
the catalyst I is p-toluenesulfonic acid.
3. The process for producing a citral norbornyl acetal derivative according to claim 2, characterized by comprising the steps of:
(1) dissolving citral dimethyl acetal, borneol and a catalyst I in an organic solvent I, carrying out distillation reaction under a stirring state, tracking the reaction process by using thin-layer chromatography, and continuously supplementing the organic solvent I lost by distillation;
(2) adding saturated sodium bicarbonate until the pH value of the system is 7-8, filtering to remove insoluble substances, separating the liquid, collecting an organic layer, and removing water;
(3) filtering, removing solvent under reduced pressure, separating by column chromatography, eluting with petroleum ether and ethyl acetate at volume ratio of 6:1 to obtain yellowish liquid as citral-di-bornyl acetal derivative.
4. A process for producing a citral norbornyl acetal derivative according to claim 3, characterized in that:
the citral dimethyl acetal and the borneol in the step (1) are mixed according to a molar ratio of 1: 2-2.5;
the dosage of the organic solvent I in the step (1) is calculated according to the proportion of 2.5-3 mL of the organic solvent I per gram of the reaction substance;
the mass amount of the catalyst I in the step (1) is 0.2-0.8% of the mass of the citral.
5. A process for producing a citral norbornyl acetal derivative according to claim 3, characterized in that:
the organic solvent I in the step (1) is one or two of chloroform and toluene.
6. A process for producing a citral norbornyl acetal derivative according to claim 3, characterized in that:
the stirring speed in the step (1) is 800-1400 r/min;
the distillation reaction in the step (1) is carried out for 4-12 hours at 62-68 ℃;
the step (2) of water removal is to use anhydrous sodium sulfate to remove water;
the filler used in the column chromatography in the step (3) is silica gel with 100-400 meshes;
the column chromatography method in the step (3) comprises the following steps: and (3) sampling, eluting impurities by using a solution of petroleum ether and ethyl acetate according to the volume ratio of more than 6:1, and then eluting by using a solution of petroleum ether and ethyl acetate according to the volume ratio of 6:1 to obtain a product of a light yellow liquid, namely the citral di-boryl acetal derivative.
7. The process for producing a citral norbornyl acetal derivative according to claim 6, characterized in that:
the water removal in the step (2) is carried out by the following steps: anhydrous sodium sulfate with the mass 1-3 times that of the citral dimethyl acetal is used for removing water for 4-8 hours;
the solution of petroleum ether and ethyl acetate in a volume ratio of more than 6:1 in the step (3) refers to a solution prepared by mixing petroleum ether and ethyl acetate in a volume ratio of = 8-10: 1.
8. The process for producing a citral norbornyl acetal derivative according to claim 2 or 3, characterized in that:
the citral dimethyl acetal is prepared by a method comprising the following steps:
1) dissolving citral and trimethyl orthoformate in an organic solvent A, adding a catalyst A, and carrying out reflux reaction at 60-90 ℃ under a stirring state to obtain a reaction system A; the catalyst A is p-toluenesulfonic acid;
2) adding a saturated sodium bicarbonate aqueous solution into the reaction system A until the pH value is = 7-8 to remove p-toluenesulfonic acid, and concentrating under reduced pressure; then extracting with an organic solvent B, collecting an organic layer, and further removing water;
3) filtering, removing solvent under reduced pressure, separating by column chromatography, and eluting with petroleum ether and ethyl acetate at volume ratio of 10:1 to obtain light yellow liquid (citral dimethyl acetal).
9. The process for producing a citral norbornyl acetal derivative according to claim 8, characterized in that:
the molar amount of trimethyl orthoformate in the step 1) is 3-4 times of that of citral;
the organic solvent A in the step 1) is alcohol;
the mass usage amount of the catalyst A in the step 1) is 0.2-0.8% of the mass of the citral;
the rotating speed of stirring in the step 1) is 800-1400 r/min;
the temperature of the reflux reaction in the step 1) is 68-80 ℃;
the reflux reaction time in the step 1) is 4-8 hours;
the organic solvent B in the step 2) is one or at least two of dichloromethane and chloroform;
the step 2) of water removal is to use anhydrous sodium sulfate to remove water;
the water removal in the step 2) is carried out by the following steps: anhydrous sodium sulfate with the mass 1-3 times that of the citral is used for dewatering for 4-8 hours;
the filler used for the column chromatography in the step 3) is silica gel with 100-400 meshes
The column chromatography method in the step 3) comprises the following steps: and (3) sampling, eluting impurities by using a solution of petroleum ether and ethyl acetate according to the volume ratio of more than 10:1, and then eluting by using a solution of petroleum ether and ethyl acetate according to the volume ratio of 10:1 to obtain a product of a light yellow liquid, namely the citral di-boryl acetal derivative.
10. The use of a citral norbornyl acetal derivative according to claim 1 in the preparation of acid sensitive small molecule bacteriostatic drug monomers.
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| CN111763155B (en) * | 2020-06-18 | 2022-11-25 | 中国农业科学院油料作物研究所 | Citral oxime ester compound and synthetic method and application thereof |
| CN113337589A (en) * | 2021-05-24 | 2021-09-03 | 华南理工大学 | Method for screening genes related to synthesis of target compound and application |
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| DE19509697A1 (en) * | 1995-03-08 | 1996-09-12 | Schering Ag | New borneol ester of 3-amino-2-hydroxy-3-phenyl-propionic acid or deriv. |
| DE19930721C2 (en) * | 1999-07-05 | 2001-12-20 | Roehm Gmbh | Process for the production and process inhibition of isobornyl methacrylate |
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| DE19509697A1 (en) * | 1995-03-08 | 1996-09-12 | Schering Ag | New borneol ester of 3-amino-2-hydroxy-3-phenyl-propionic acid or deriv. |
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| CN108558621A (en) | 2018-09-21 |
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