CN108101855B - Preparation method and application of amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle - Google Patents
Preparation method and application of amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle Download PDFInfo
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Abstract
The invention discloses a preparation method and biological activity of a compound for preventing and treating cucumber mosaic virus, namely an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle, and the compound is represented by the following general formula (I) and a preparation method thereof. The invention introduces an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle, which is synthesized by a microwave one-pot method by taking 2-amino-4-piperidyl-6-methylpyrimidine, substituted aldehyde and malonate as raw materials and p-xylene as a solvent. Compounds I of the invention2Has good inhibition effect on cucumber mosaic virus and tobacco ralstonia solanacearum.
Description
Technical Field
The invention relates to the technical field of chemistry, in particular to an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle, a preparation method of the compound and an application of the compound in inhibiting cucumber mosaic virus and tobacco ralstonia solanacearum.
Background
Cucumber Mosaic Virus (CMV) belongs to the family of brommosaic viruses and is one of the viruses with the widest distribution, the heaviest harm and the most economic importance. The distribution and harm of the virus exist in the left and right tobacco and vegetable planting areas worldwide, the yield and quality are reduced even the harvest is caused after the tobacco and the vegetables are infected, and the serious economic loss is brought to the agricultural production (Shenxiao, Song Shuang, Rongjing, Zhang Xin, Anderong, tobacco cucumber mosaic virus resistant polysaccharide screening and the influence thereof on the activity of tobacco defensive enzyme [ J ] microbiology report, 2013,53(08): 882-. At present, the practical varieties of the effective and satisfactory plant virus resisting agents are not many, particularly, the specific therapeutic agents are fewer, and the control effect of the reported agents in the field practical application is mostly below 60%. Therefore, the development of a novel high-efficiency anti-cucumber mosaic virus medicament is imminent.
Tobacco is an important economic crop, and the tobacco bacterial wilt caused by Ralstonia solanacearum is a huge hazard. The disease is a typical vascular bundle disease, all parts of roots, stems and leaves of tobacco can be infected, the roots of diseased plants become black and rot, and destructive hazards are caused to the tobacco (Liuwei, Liupeng, Shenying, Antiancii, Julongong, Anderong, screening and identification of the tobacco bacterial wilt antagonistic bacillus and the bacteriostatic activity thereof are initially detected [ J ]. the academy of science and technology of northwest agroforestry (Nature science edition), 2014,42(02): 123-. At present, the method is mainly used in the tobacco producing provinces in China. At present, no ideal disease-resistant variety exists for ralstonia solanacearum, and the development of effective chemical control agents is paid attention by domestic researchers.
In 1995, Shinshi et al (Shinshi, Hu Zhi, Chen Jia, Chen Wei Xin, Wulinsen. A new agricultural antibiotic-Ningnanmycin [ J ]. Microbiol., 1995,35(5):368 cake 374.) extracted cytosine nucleoside peptide type antibiotic ningnanmycin from fermentation broth of S.noursensis S.Wenchang variety. The multi-point prevention and control test is carried out in Sichuan province and Yunnan province of China, and the demonstration result shows that: the effect of Ningnanzymosin on preventing and treating tobacco mosaic disease is 69.4-95.4%, the average yield increasing effect is 26.1%, the effect is superior to the effect of carbendazim, chlorothalonil and NC-83, and the internal quality of tobacco leaves can be obviously improved. After the application interval in the greenhouse is 3-10 days, the CMV, TMV and PVY are respectively inoculated manually, and experiments show that the control effect of the ningnanmycin on the tobacco mosaic disease caused by the CMV and TMV is up to 90.9 percent and 92.9 percent, and the control effect on the tobacco mosaic disease caused by the PVY is up to 53.8 percent.
Jasmonates (jasmonates, Jas) is a newly discovered plant endogenous hormone, and representatives are Jasmonic Acid (JA) and Methyl Jasmonate (MJ). Creelmna et al (
Creelmna R a; mellout J E.biosynthes and action of jasmocations in plnat [ J ]. Annual Review of Plant Physiology and Plant Molecular Biology,1997,48:355-381) found that JAs plays a role in Plant disease resistance, is one of the transmitters of disease resistance signals, and participates in local and systemic resistance in Plant disease resistance.
In order to create a novel high-efficiency cucumber mosaic virus resistant agent, the invention utilizes the active group splicing principle to introduce pyrimidine heterocycle into an amino acid ester structure on the basis of earlier work, so as to design and synthesize a series of amino acid ester compounds containing 4-piperidyl-6-methyl pyrimidine heterocycle, and expect to screen out high-activity cucumber mosaic virus and tobacco ralstonia solanacearum resistant medicines.
Disclosure of Invention
The invention aims to provide an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle and having the activity of resisting cucumber mosaic virus and ralstonia solanacearum and a preparation method thereof.
The other purpose of the method is to prevent and treat Cucumber Mosaic Virus (CMV) and ralstonia solanacearum.
The invention relates to an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle, which has a general formula as shown in the following formula (I):
wherein: r1Is phenyl, monosubstituted phenyl, para-monosubstituted methoxyphenyl, para-monosubstituted methylphenyl, cyclohexyl or furylmethyl; r2Methyl or ethyl.
The invention relates to an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle, which has been synthesized by the following steps: compound I1：
Diethyl-2- (((4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (benzyl) malonic acid;
compound I2：
Diethyl-2- ((4- (methoxyphenyl) ((4-methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (methyl) malonic acid;
compound I3：
Diethyl-2- ((4-chlorophenyl) (4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (methyl) malonic acid;
compound I4：
Diethyl-2- (cyclohexyl) ((4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (methyl) malonic acid;
compound I5：
Dimethyl-2- (((4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (benzyl) malonic acid;
compound I6：
Dimethyl-2- (((4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (benzyl) malonic acid;
compound I7：
Diethyl-2- (furan-2-yl) ((4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (methyl) malonic acid;
compound I8：
Diethyl-2- (cyclohexyl) ((4- (methyl-6-piperidin-1-yl) pyrimidin-2-yl) amino) (methyl) malonic acid;
the invention relates to a preparation method of an amino acid ester compound containing a 4-piperidyl-6-methylpyrimidine heterocycle, which takes 2-amino-4-piperidyl-6-methylpyrimidine, substituted aldehyde and malonate as raw materials and takes p-xylene as a solvent to synthesize the amino acid ester compound containing the 4-piperidyl-6-methylpyrimidine heterocycle by a microwave one-pot method, and the synthetic route is as follows:
wherein partial compound (I)1-I2) The structural characteristics of (A) are as follows:
the invention relates to a preparation method of an amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle, which comprises the following steps:
putting 2-amino-4-piperidyl-6-methylpyrimidine, substituted aldehyde and malonate into a single-mouth bottle, adding p-xylene, heating to 100 ℃ by microwave, reacting for 50 minutes, recovering the p-xylene under reduced pressure, and separating by column chromatography (petroleum ether: ethyl acetate: 4:1V/V) to obtain a target product I1-I8，
The application of the 4-piperidyl-6-methylpyrimidine heterocycle-containing amino acid ester compound refers to a medicine or medicament with an inhibiting effect on cucumber mosaic virus and tobacco ralstonia solanacearum.
The invention has the beneficial effects that: the invention synthesizes the amino acid ester compound of the 4-piperidyl-6-methylpyrimidine heterocycle, which has the inhibiting effect on cucumber mosaic virus and tobacco ralstonia solanacearum. At present, no report that the compounds can be simultaneously used for preventing and treating cucumber mosaic virus and tobacco ralstonia solanacearum exists, and the method has the advantages of reasonable synthetic route, easily obtained synthetic raw materials, simple operation and higher reaction yield. And the compounds I of the invention2Has inhibitory effect on cucumber mosaic virus and tobacco ralstonia solanacearum. And I2In the aspect of preventing and treating cucumber mosaic virus, whether the activity is treatment, protection or passivation,are all superior to the reference medicament ningnanmycin. Compound I2The inhibition rate of the bacterial wilt of tobacco at the concentration of 200ug/mL and 100ug/mL is 100 percent equivalent to that of commercial control medicament, namely thiabendazole copper. In addition, the invention also relates to the compound I which is optimal for biological activity2The preparation method of (A) was intensively studied and finally determined that the compound I of the present invention has the optimum activity2The continuous production preparation method.
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FIG. 1 is a schematic of the continuous preparation of I2 using an MCT microreactor.
Detailed Description
Example 1: compound I1The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), benzaldehyde (0.001mol), diethyl malonate (0.0015mol) and p-xylene (30mL) as a solvent were added, the reaction was terminated after 50 minutes at 100 ℃ in a microwave, the p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
Example 2: compound I2The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), 4-methoxybenzaldehyde (0.001mol), diethyl malonate (0.0015mol) were added, p-xylene (30mL) was added as a solvent, the reaction was terminated after 50 minutes at 100 ℃ in a microwave, p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
Example 3: compound I3The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), 4-chlorobenzaldehyde (0.001mol), diethyl malonate (0.0015mol) and p-xylene (30mL) as a solvent were added, the reaction was terminated after 50 minutes at 100 ℃ in a microwave, the p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
Example 4: compound I4The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), cyclohexylformaldehyde (0.001mol), diethyl malonate (0.0015mol), p-xylene (30mL) as a solvent were added, the reaction was terminated after 50 minutes at 100 ℃ in a microwave, p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
Example 5: compound I5The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), benzaldehyde (0.001mol), dimethyl malonate (0.0015mol), p-xylene (30mL) as a solvent were added, the reaction was terminated after 50 minutes at 100 ℃ in a microwave, p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
Example 6: compound I6The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), p-tolualdehyde (0.001mol), and dimethyl malonate (0.0015mol) were added, p-xylene (30mL) was added as a solvent, the reaction was terminated after 50 minutes at 100 ℃ with a microwave, p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
Example 7: compound I7The synthesis of (2):
in a 100mL single-neck bottle, 2-amino-4-piperidyl-6-methylpyrimidine (0.001mol), furfural (0.001mol) and dimethyl malonate (0.0015mol) are added, p-xylene (30mL) is added as a solvent, the reaction is ended after 50 minutes at 100 ℃ by microwave, the p-xylene is recovered under reduced pressure, and the target product is obtained by column chromatography (petroleum ether: ethyl acetate: 4: 1V/V).
Example 8: compound I8The synthesis of (2):
in a 100mL single-neck flask, 2-amino-4-piperidinyl-6-methylpyrimidine (0.001mol), cyclohexylformaldehyde (0.001mol), dimethyl malonate (0.0015mol), p-xylene (30mL) as a solvent were added, the reaction was terminated after 50 minutes at 100 ℃ in a microwave, p-xylene was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate 4: 1V/V).
The yield, physical form and elemental analysis of the 4-piperidyl-6-methylpyrimidine heterocycle-containing amino acid ester compounds synthesized in examples 1 to 8 are shown in Table 1, and NMR spectra (NMR)1H NMR data shown in Table 2, nuclear magnetic resonance carbon Spectroscopy (C:)13C NMR) data is shown in table 3, infrared spectroscopy (IR) data is shown in table 4, and Mass Spectroscopy (MS) data is shown in table 5:
TABLE 1 physicochemical Properties and elemental analysis of the target Compounds
TABLE 2 of the target Compounds1H NMR data
TABLE 3 preparation of the target compounds13C NMR data
TABLE 4 Infrared data for target Compounds
| Compound (I) | IR(KBr)(cm-1) |
| I1 | 3378,2973,1736,1553,1431,1237,1172,826,791 |
| I2 | 3481,2962,1738,1571,1446,1243,1163,858,790 |
| I3 | 3411,2927,1742,1567,1465,1258,1169,920,762 |
| I4 | 3379,2980,1733,1578,1454,1243,1190,852,788 |
| I5 | 3391,2969,1727,1570,1437,1247,1173,858,779 |
| I6 | 3490,2961,1741,1569,1448,1251,1171,864,790 |
| I7 | 3400,2926,1728,1579,1451,1243,1172,927,778 |
| I8 | 3388,2991,1730,1577,1454,1240,1165,881,792 |
TABLE 5 Mass Spectrometry of target Compounds
| Compound (I) | MS(ESI):m/z |
| I1 | 441([M+H]+),463([M+Na]+),479([M+K]+). |
| I2 | 471([M+H]+),493([M+Na]+),509([M+K]+). |
| I3 | 475([M+H]+),497([M+Na]+),513([M+K]+). |
| I4 | 447([M+H]+),469([M+Na]+),485([M+K]+). |
| I5 | 413([M+H]+),435([M+Na]+),451([M+K]+). |
| I6 | 427([M+H]+),449([M+Na]+),465([M+K]+). |
| I7 | 403([M+H]+),425([M+Na]+),441([M+K]+). |
| I8 | 419([M+H]+),441([M+Na]+),457([M+K]+). |
Example 9 therapeutic, inactivating and protective Activity of the Compounds of interest against cucumber mosaic Virus
(1) Test method
A. Purification of viruses
A circumferential snow leveling method (Zhou, X.P.; Xu, Z.X.; Xu, J.; Li, D.B.J.south Chin.Agric.Univ.1995,16,74-79) is adopted, and the CMV system infects the upper leaves of the host Nicotiana tabacum.L plant for more than 3 weeks, and the upper leaves are homogenized in phosphate buffer solution, filtered by double-layer gauze, centrifuged at 8000g, treated by 2 times of polyethylene glycol, centrifuged again, and the precipitate is suspended by the phosphate buffer solution, so that the CMV refined liquid is obtained. The whole experiment was carried out at 4 ℃ and the absorbance at a wavelength of 260nm was measured with an ultraviolet spectrophotometer and the virus concentration was calculated according to the formula.
Concentration of virus (mg/mL) ═ A260X dilution times)/E0.1％ 1cm 260nm
Wherein E represents the extinction coefficient, i.e. the value of the optical absorption (optical density) at an optical path length of l cm for a suspension at a concentration of 0.1% (1mg/mL) at a wavelength of 260 nm. E of CMV0.1％ 1cm 260nmIs 5.0.
B. Active therapeutic effect of agents on CMV infection: selecting 5-6 leaf-stage Portulaca oleracea Linne with ever growing vigor, topping, spreading emery on all leaves, and dipping virus juice (6 × 10)-3mg/mL) whole leaf virus, air-dried naturally and washed with clear water. After the leaves are dry, the left half leaf is lightly coated with the medicament by using a brush pen, the concentration of the corresponding solvent is coated on the right half leaf to be used as a control, the number of the dead spots is recorded after 6 to 7 days, and the inhibition rate is calculated according to the following formula.
C. In vivo protection of CMV infection by Agents
Live protection of agents against CMV infestation: selecting 5-6 leafs of Portulaca oleracea, topping, lightly applying the medicinal preparation to the left half leaf and the solvent with corresponding concentration to the right half leaf with a writing brush, spreading emery after 24 hr, and dipping virus juice (6 × 10) with a row pen-3mg/mL) of the whole leaf, washing with clear water, recording the number of dead spots after 6-7 days, and calculating the inhibition rate according to the following formula.
D. In vivo inactivation of CMV infection by Agents
Selecting 5-6-leaf summer purslane with long growth vigor, topping, spreading carborundum uniformly on the whole leaf, and adding phosphoric acid buffer solution to the CMV; viral dilution to 6X 10-3mg/mL, mixing and passivating the compound and virus juice with the same volume for 30 minutes, manually rubbing the mixture by using a row pen to inoculate the mixture in the left half of Portulaca oleracea L, which is scattered with carborundum, and mixing the solvent and the virus juice with corresponding doses to inoculate the mixture in the right half of Portulaca oleracea L, which is scattered with the carborundum, recording the number of dead spots after 6-7 days, and calculating the inhibition rate according to the following formula.
X％＝(CK－T)/CK×100
X is relative inhibition (%);
CK, average number of dead spots of half leaves without application of the medicament;
t is the average number of scorched spots of half leaves of the applied medicament;
where, CK and T are the average of three replicates of each group.
(2) Biological test results
TABLE 6 therapeutic, protective and inactivating activity of target compounds on cucumber mosaic virus
| Compound (I) | Concentration (μ g/mL) | Therapeutic Effect (%) | Protective Effect (%) | Passivation Effect (%) |
| I1 | 500 | 42.9±2.8 | 47.8±1.3 | 64.2±1.5 |
| I2 | 500 | 54.5±2.2 | 67.2±1.6 | 93.1±3.4 |
| I3 | 500 | 33.1±3.1 | 53.4±2.1 | 63.2±2.5 |
| I4 | 500 | 23.3±2.1 | 33.5±2.6 | 52.3±2.8 |
| I5 | 500 | 22.3±3.1 | 38.2±2.3 | 51.1±1.2 |
| I6 | 500 | 42.3±0.9 | 48.3±1.0 | 58.8±0.9 |
| I7 | 500 | 24.5±1.1 | 37.2±1.3 | 44.1±1.2 |
| I8 | 500 | 46.3±2.1 | 59.9±3.7 | 82.3±1.8 |
| Ningnanmycin | 500 | 50.0±2.2 | 64.6±2.8 | 92.3±2.7 |
The anti-CMV activity of the target compound is tested by adopting a half-leaf withered spot method with the concentration of 500mg/L and taking ningnanmycin as a contrast medicament, and the results of the biological activity measurement in Table 6 show that the amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle has moderate to excellent inhibitory activity on CMV, wherein I2Is superior to the Ningnanmycin which is a contrast medicament in the aspects of treatment, protection and passivation.
In order to further research the anti-CMV activity of amino acid ester compounds containing 4-piperidyl-6-methylpyrimidine heterocycle, we determined I in the compounds2Treatment of EC50The values, results are shown in Table 7.
TABLE 7 EC for CMV therapeutic Activity of partial target Compounds50Value of
| Compound (I) | EC50(μg/mL) |
| I2 | 213.2±1.9 |
| Ningnanmycin | 298.5±2.7 |
As a result, it can be seen that I2EC for CMV protective Activity50213.2 mug/mL, which is better than the control drug ningnanmycin 298.5 mug/mL.
Example 10, test method for tobacco bacterial wilt:
the concentrations of the tested compounds are respectively 100ug/mL and 200ug/mL, DMSO is dissolved in a culture medium to be used as a blank control, thiediazole copper is used as a control agent, the tobacco bacterial wilt bacterium is subjected to streak culture on an NA solid culture medium, and the obtained product is placed in a constant-temperature incubator at 30 ℃ to be cultured until a single colony grows out. Selecting single colony with pink center and more white edges by using a inoculating ring, putting the single colony into an NB liquid culture medium, and carrying out shake culture in a constant temperature shaking table at 30 ℃ and 180rpm until the single colony reaches logarithmic phase for later use. Respectively preparing the compound and the contrast agent into 5mL of toxic NB liquid culture medium with the concentrations of 100ug/mL and 200ug/mL, adding into a test tube, adding into 40uL of NB liquid culture medium containing tobacco bacterial wilt original bacteria, shake culturing in a constant temperature shaking table at 30 deg.C and 180rpm for 48h, and measuring OD of the bacterial liquid with each concentration on a spectrophotometer595Value, and additionally determining the OD of the sterilized NB-containing liquid medium at the corresponding concentration595The value is obtained.
OD value of bacteria-containing culture medium-OD value of sterile culture medium
The inhibition ratio [ (% OD value of control medium liquid-corrected OD value of toxic medium)/OD value of control medium liquid ] X100%.
As can be seen from the above table: under the test concentration, the target compound has certain inhibitory activity on pathogenic bacteria of tobacco bacterial wilt, wherein the compound I2The inhibition rate of the bacterial wilt of tobacco at the concentration of 200ug/mL and 100ug/mL is 100 percent equivalent to that of commercial control medicament, namely thiabendazole copper.
Example 10 continuous preparation of I Using MCT microreactor2。
500mL of toluene solution of 0.1 mol/L2-amino-4-piperidyl-6-methylpyrimidine is put into a bottle A (marked as bottle A), and 500mL of toluene solution of p-methoxybenzaldehyde and diethyl malonate, the concentration of which is 0.1mol/L, is put into a bottle B; the bottle A and the bottle B are respectively pushed by an MPK2005 medium-pressure constant-flow pump at the flow rate of 10mL/min, the mixture enters an MCT micro-reactor (the reaction temperature of the MCT micro-reactor is set to be 90 ℃), the reaction is stopped after 50 minutes, the p-xylene in a product collecting bottle is recovered under reduced pressure, and 34.5g of a target product I is obtained after the product is separated by column chromatography (petroleum ether: ethyl acetate is 4:1V/V)2Yield, yield: 90.0 percent. The MCT microreactor can be used for continuously producing gram-grade target product I with high yield2。
The embodiment of the invention is supplemented with the technical scheme of the invention. The invention has the advantages of simple synthetic route and higher yield, and obtains a novel and efficient medicament for preventing and treating cucumber mosaic virus and tobacco ralstonia solanacearum.
Claims (6)
1. An amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle is characterized in that: the general formula is shown as the following formula (I):
wherein: r1Is phenyl, p-methoxyphenyl, p-methylphenyl or cyclohexyl; r2Methyl or ethyl.
2. An amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle is characterized in that:
wherein, I1：R1＝Ph R2＝Et；
I2：R1＝4-OMe-Ph R2＝Et；
I3：R1＝4-Cl-Ph R2＝Et；
I4：R1Cyclohexyl radical R2＝Et；
I5：R1＝Ph R2＝Me；
I6：R1＝4-Me-Ph R2＝Me；
I7：R12-furyl R2＝Me；
I8：R1Cyclohexyl radical R2＝Me。
3. The method for synthesizing an amino acid ester compound containing a 4-piperidinyl-6-methylpyrimidine heterocycle as claimed in claim 1 or 2, wherein: the amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle is synthesized by a microwave one-pot method by taking 2-amino-4-piperidyl-6-methylpyrimidine, substituted aldehyde and malonate as raw materials and p-xylene as a solvent, and the synthetic route is as follows:
4. the method for synthesizing the amino acid ester compound containing the 4-piperidyl-6-methylpyrimidine heterocycle according to the claim 3, which is characterized in that: the microwave is heated to 100 ℃ for reaction for 50 minutes, the paraxylene is recovered under reduced pressure, and the target product is obtained by column chromatographic separation.
5. The method for synthesizing the amino acid ester compound containing the 4-piperidyl-6-methylpyrimidine heterocycle according to the claim 4, which is characterized in that: the column chromatographic separation conditions are as follows: ethyl acetate 4: 1V/V.
6. The use of the amino acid ester compound containing 4-piperidinyl-6-methylpyrimidine heterocycle according to claim 1 or 2 in the preparation of drugs and medicaments for controlling cucumber mosaic virus and ralstonia solanacearum.
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| CN101817803A (en) * | 2010-04-29 | 2010-09-01 | 贵州大学 | Beta-amino acid esters having optical activity and containing benzothiazole groups and synthetic method and application thereof |
| CN103980225A (en) * | 2014-04-30 | 2014-08-13 | 淮海工学院 | Synthetic method of beta-amino acid with thiazole ring connected to nitrogen |
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| CN101817803A (en) * | 2010-04-29 | 2010-09-01 | 贵州大学 | Beta-amino acid esters having optical activity and containing benzothiazole groups and synthetic method and application thereof |
| CN103980225A (en) * | 2014-04-30 | 2014-08-13 | 淮海工学院 | Synthetic method of beta-amino acid with thiazole ring connected to nitrogen |
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| Synthesis and Anti-TMV Activity of Dialkyl/dibenzyl 2-((6-Substituted-benzo[d]thiazol-2- ylamino)(benzofuran-2-yl)methyl) Malonates;Han Xiao et al.,;《Molecules》;20131104;第18卷;第13623-13635页 * |
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