CN115246835B - Aldrisin derivative containing hydrazone structure and preparation and application thereof - Google Patents
Aldrisin derivative containing hydrazone structure and preparation and application thereof Download PDFInfo
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Abstract
The invention relates to an Aldisin derivative containing hydrazone structure, a preparation method thereof and application thereof in the aspects of preventing and controlling plant viruses, sterilizing and killing insects, wherein the meaning of each group in the general formula is shown in the specification. The Aldisin derivative containing the hydrazone structure has excellent anti-plant virus activity, and also has broad-spectrum bactericidal activity and insecticidal activity.
Description
Technical Field
The invention relates to an Aldisin derivative containing a hydrazone structure, a preparation method thereof and application thereof in the aspects of preventing and controlling plant viruses, killing insects and sterilizing, and belongs to the technical field of agricultural protection.
Background
In 1985, schmitz group, university of octopamphlet, isolated for the first time an alkaloid Aldisin having a pyrrololactam structure from the island sponge Hymeniacidon aldis de laubenfels (j.nat. Prod.1985, 48, 47-53). In 2004, the test subject group carries out structural derivatization on an alkaloid Hymenoldinine with an Aldrisin structure, and carries out biological activity research on the derivatization, and the research result shows that the Hymenoldinine has an IC inhibiting effect on interleukin-2 and tumor necrosis factor-alpha 50 The values were 2.4. Mu.M and 1.4. Mu.M, respectively (J.Med. Chem.2004, 11, 247-259.). In the same year, the cope group has acted on hypnialdinine against six different kinases including CK1 δ (h), CK2 (h), MEK1 (h), pkcα (h), PKCbII (h), chk1 and Chk2, and biological test results indicate that: hymenoldinine has good inhibitory activity on MEK1 (h), IC thereof 50 The value was 6nM (Bioorg. Med. Chem. Lett.2004, 14, 4319-4321.). So far, there is no synthesis method of Aldisin derivatives I-1 to I-37 containing hydrazone structure and application of the derivatives I-1 to I-37 in preventing and controlling plant virus, killing insects and sterilizing.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides an Aldisin derivative containing a hydrazone structure, a preparation method thereof and application thereof in the aspects of preventing and controlling plant viruses, killing insects and sterilizing. The Aldisin derivative of the patent has good plant virus prevention and control, insecticidal activity and broad-spectrum bactericidal activity.
The Aldisin derivative containing the hydrazone structure is a compound with a structure shown in the following general formula I:
wherein R represents hydrogen, substituted or unsubstituted benzyl; the substituents of the substituted benzyl are each independently selected from one or more of hydroxy, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene;
R 1 、R 2 respectively represent hydrogen or R 1 、R 2 Is combined into
R 3 ；
R 3 Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted quinolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted thienyl group; the substituents of the substituted phenyl, the substituted quinolinyl, the substituted indolyl, the substituted pyridinyl and the substituted thiophenyl are each independently selected from one or more of halogen, C1-C6 alkyl, C1-C6 alkoxy and phenoxy.
The preparation method of the Aldisin derivative containing the hydrazone structure comprises the following steps: aldrisin is used as a raw material, ethanol is used as a solvent, and the mixture is subjected to condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain the hydrazone-containing derivative.
The preparation method of the Aldisin derivative containing the hydrazone structure comprises the following steps: taking Aldisin as a raw material, taking ethanol as a solvent, and carrying out condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain a hydrazone-containing derivative; ethanol is used as a solvent, and the solvent and aromatic aldehyde are subjected to addition elimination reaction at room temperature to obtain hydrazone with a diimine structure.
The preparation method of the Aldisin derivative containing the hydrazone structure comprises the following steps: aldrisin and benzyl bromide are used as reactants, sodium carbonate is used as alkali, acetonitrile is used as a solvent, and a compound A is obtained under the condition of heating and refluxing; the compound A is used as a raw material, ethanol is used as a solvent, and the compound A and hydrazine hydrate are subjected to condensation reaction under the condition of heating reflux to obtain the hydrazone derivative protected on pyrrole nitrogen.
The preparation method of the Aldisin derivative containing the hydrazone structure comprises the following steps: the hydrazone derivative protected on pyrrole nitrogen is taken as a raw material, ethanol is taken as a solvent, and an addition elimination reaction is carried out with aromatic aldehyde at room temperature, so as to obtain the hydrazone of the hydrazone derivative diimine structure protected on pyrrole nitrogen.
The Aldisin derivative containing the hydrazone structure in the general formula shows good tobacco mosaic virus resistance.
The Aldisin derivative containing the hydrazone structure with the general formula has the activity of killing myxomycetes, cotton bollworms, corn borers, plutella xylostella and mosquito larvae.
The Aldisin derivative containing hydrazone structure of the general formula shows bactericidal activity on 14 pathogenic bacteria: cucumber wilt, peanut brown spot, apple ring spot, wheat sheath blight, corn small spot, watermelon anthracnose, rice bakanae, tomato early blight, wheat gibberella, rice blast, phytophthora capsici, rape sclerotium, cucumber gray mold and rice sheath blight.
The invention provides an Aldisin derivative containing a hydrazone structure, which is a compound shown in a general formula I:
wherein R represents hydrogen, substituted or unsubstituted benzyl; the substituents of the substituted benzyl are each independently selected from one or more of hydroxy, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene;
R 1 、R 2 respectively represent hydrogen or R 1 、R 2 Is combined into
R 3 ；
R 3 Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted quinolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted thienyl group; the substituents of the substituted phenyl, the substituted quinolinyl, the substituted indolyl, the substituted pyridinyl and the substituted thiophenyl are each independently selected from one or more of halogen, C1-C6 alkyl, C1-C6 alkoxy and phenoxy.
In the present invention, specific examples of the C1-C6 alkyl group may be, for example: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl and the like.
The C1-C6 hydrocarbon group may be selected from the specific examples of the alkyl groups described above and is subject to the corresponding limitations.
The C1-C6 alkoxy group may be an alkoxy group formed by the specific examples of the alkyl groups satisfying the definition of 1 to 6 carbon atoms described above.
Preferably, R represents hydrogen, substituted or unsubstituted benzyl; the substituent of the substituted benzyl is independently selected from one or more of hydroxyl, F, cl, br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy and n-pentoxy;
R 1 、R 2 respectively represent hydrogen or R 1 、R 2 Is combined into
R 3 ；
R 3 Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted quinolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted thienyl group; the substituents of the substituted phenyl, substituted quinolinyl, substituted indolyl, substituted pyridinyl, substituted thiophenyl are each independently selected from one or more of F, cl, br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, phenoxy.
In a preferred embodiment of the present invention, the compound of formula I is selected from one of the compounds shown in the following formulas:
the invention provides a preparation method of an Aldisin derivative containing a hydrazone structure, which comprises the following steps: aldrisin is used as a raw material, ethanol is used as a solvent, and the mixture is subjected to condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain the hydrazone-containing derivative.
The invention provides a preparation method of an Aldisin derivative containing a hydrazone structure, which comprises the following steps: aldrisin is used as a raw material, ethanol is used as a solvent, and the mixture is subjected to condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain a hydrazone derivative, ethanol is used as a solvent, and the hydrazone derivative and aromatic aldehyde are subjected to addition elimination reaction at room temperature to obtain hydrazone with a diimine structure.
The invention provides a preparation method of an Aldisin derivative containing a hydrazone structure, which comprises the following steps: aldrisin and benzyl bromide are used as reactants, sodium carbonate is used as alkali, acetonitrile is used as a solvent, and a compound A is obtained under the condition of heating and refluxing; the compound A is used as a raw material, ethanol is used as a solvent, and the compound A and hydrazine hydrate are subjected to condensation reaction under the condition of heating reflux to obtain the hydrazone derivative protected on pyrrole nitrogen.
The invention provides a preparation method of an Aldisin derivative containing a hydrazone structure, which comprises the following steps: the hydrazone derivative protected on pyrrole nitrogen is taken as a raw material, ethanol is taken as a solvent, and an addition elimination reaction is carried out with aromatic aldehyde at room temperature, so as to obtain the hydrazone of the hydrazone derivative diimine structure protected on pyrrole nitrogen.
Therein, R, R 3 As described hereinabove, the present invention is not described in detail herein.
The invention provides application of the Aldisin derivative containing the hydrazone structure in the aspect of anti-plant virus activity.
The Aldisin derivative containing the hydrazone structure provided by the invention has excellent anti-plant virus activity, and the Aldisin derivative containing the hydrazone structure shown in the general formula shows good anti-tobacco mosaic virus activity.
The Aldisin derivative containing the hydrazone structure provided by the invention has higher insecticidal activity, and particularly has higher insecticidal activity on one or more of armyworms, cotton bollworms, corn borers, plutella xylostella and mosquito larvae.
The invention provides an application of the Aldisin derivative containing the hydrazone structure in sterilization.
The Aldisin derivative containing the hydrazone structure has higher bactericidal activity, and particularly aims at one or more pathogenic bacteria causing cucumber wilt, peanut brown spot, apple ring, wheat sharp eyespot, corn small spot, watermelon anthrax, rice bakanae, tomato early blight, wheat gibberella, rice blast, phytophthora capsici, rape sclerotium, cucumber gray mold and rice sharp eyespot.
The invention also provides a method for killing insects by adopting the Aldisin derivative containing the hydrazone structure as an anti-plant virus agent.
The invention also provides a method for killing insects by using the Aldisin derivative containing the hydrazone structure as an insecticide.
The invention also provides a method for sterilizing by using the Aldisin derivative containing the hydrazone structure as a bactericide.
The following examples and green test results are intended to further illustrate the invention and are not meant to limit the invention.
Detailed Description
The following examples and green test results are intended to further illustrate the invention and are not meant to limit the invention.
Example 1: synthesis of Aldrisin derivative I-1.
Synthesis of I-1: aldrisin (164 mg,1.00 mmol) was weighed into a 50mL round bottom flask, 10mL absolute ethanol was added, then hydrazine hydrate was added, the reaction was heated to reflux for 4h, and TLC detection was complete. Pressurizing to remove solvent, and then re-dissolvingEthanol is added newly, repeated pressurization and desolventizing are carried out, 178mg of white solid is obtained, the yield is quantified, and the melting point is: 258-260 ℃. 1 H NMR(400MHz，DMSO-d 6 ) δ11.30(s，1H)，7.75(t，J＝5.3Hz，1H)，6.82(t，J＝2.8Hz，1H)，6.36(t，J＝2.7Hz，1H)，6.05(s， 2H)，3.24(q，J＝5.4Hz，2H)，2.54(d，J＝5.4Hz，2H). 13 C NMR(100MHz，DMSO-d 6 )δ164.9， 143.4，126.2，122.6，122.3，106.8，38.1，30.5.HRMS(ESI)：calcd for C 8 H 11 N 4 O[M+H] + 179.0927， found 179.0923.
Example 2: and (3) synthesizing Aldrisin derivatives I-2 to I-14.
Synthesis of I-2: i-1 (356 mg,2 mmol) was weighed into a 100mL round bottom flask, 40mL absolute ethanol was added, followed by benzaldehyde (318 mg,3 mmol) and reacted at room temperature for 4h, and TLC detection was complete. Desolventizing under reduced pressure, separating by column chromatography to obtain 490mg of yellow solid with 92% yield and melting point of 186-188 ℃. 1 H NMR(400MHz，DMSO-d 6 )δ11.81(s，1H)，8.45(s，1H)，8.08(t，J＝5.1Hz，1H)，7.88-7.82(m，2H)，7.51-7.42(m，3H)，6.97(t，J＝2.8Hz， 1H)，6.71(t，J＝2.6Hz，1H)，3.32-3.26(m，2H)，3.18-3.07(m，2H). 13 C NMR(100MHz， DMSO-d 6 )δ163.0，162.9，156.8，134.5，130.7，128.8，128.0，126.2，122.9，122.2，107.7，37.6，31.6. HRMS(ESI)：calcd for[M+H] + 165.0659，found 165.0660.HRMS(ESI)：calcd for C 15 H 15 N 4 O [M+H] + 267.1240，found 267.1235.
Synthesis of I-3: the synthesis method is the same as I-2. Yellow solid, yield 89%, melting point 212-213 ℃. 1 H NMR(400 MHz，CDCl 3 )δ10.28(s，1H)，8.44(s，1H)，7.75(d，J＝8.4Hz，2H)，7.46(d，J＝8.4Hz，2H)，6.99 (dt，J＝13.3，2.8Hz，2H)，6.78(d，J＝5.4Hz，1H)，3.51(q，J＝5.0Hz，2H)，3.39-3.30(m，2H)， 1.35(s，9H). 13 C NMR(100MHz，CDCl 3 )δ165.1，162.4，157.9，154.3，132.0，128.2，125.7，125.1， 125.0，122.8，109.0，39.0，35.0，31.4，31.2.HRMS(ESI)：calcd for C 19 H 23 N 4 O[M+H] + 323.1866， found 323.1862.
Synthesis of I-4: the synthesis method is the same as I-2. Yellow solid, yield 92%, melting point 252-254 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.85(s，1H)，8.47(s，1H)，8.10(t，J＝5.1Hz，1H)，7.90-7.84(m，2H)，7.59- 7.52(m，2H)，6.97(t，J＝2.8Hz，1H)，6.71(t，J＝2.6Hz，1H)，3.29(q，J＝5.1Hz，2H)，3.13(d，J＝ 9.8Hz，2H). 13 C NMR(100MHz，DMSO-d 6 )δ163.8，163.5，156.2，135.7，133.9，130.1，129.4， 126.8，123.3，122.7，108.3，38.0，32.0.HRMS(ESI)：calcd for C 15 H 14 ClN 4 O[M+H] + 301.0851， found 301.0846.
Synthesis of I-5: the synthesis method is the same as I-2. Yellow solid, yield 93%, melting point 226-228 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.87(s，1H)，8.63(d，J＝7.6Hz，1H)，8.15-8.02(m，2H)，7.83-7.71(m，1H)， 7.54(t，J＝7.8Hz，1H)，6.98(dd，J＝6.8，3.9Hz，1H)，6.77-6.66(m，1H)，3.28(s，2H)，3.12(s， 2H). 13 C NMR(100MHz，DMSO-d 6 )δ164.3，162.9，151.7，135.9，134.7，130.6，129.5，129.2， 127.9，126.6，122.5，122.3，108.0，37.5，31.8.HRMS(ESI)：calcd for C 15 H 13 Cl 2 N 4 O[M+H] + 335.0461，found 335.0461.
Synthesis of I-6: the synthesis method is the same as I-2. Yellow solid, yield 95%, melting point 272-274 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.91(s，1H)，8.64(s，1H)，8.13(t，J＝5.1Hz，1H)，8.07(d，J＝2.5Hz，1H)， 7.99(d，J＝2.5Hz，1H)，6.99(t，J＝2.8Hz，1H)，6.74(t，J＝2.7Hz，1H)，3.30(q，J＝5.2Hz，2H)， 3.14(t，J＝5.3Hz，2H). 13 C NMR(100MHz，DMSO-d 6 )δ164.9，162.9，151.4，134.9，133.6，132.5， 131.3，130.7，126.9，125.8，122.4，122.3，108.0，37.5，31.9.HRMS(ESI)：calcd for C 15 H 12 Cl 3 N 4 O [M+H] + 369.0071，found 369.0066.
Synthesis of I-7: the synthesis method is the same as I-2. Yellow solid, yield 88%, melting point 240-242 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.79(s，1H)，8.42(s，1H)，8.07(t，J＝5.0Hz，1H)，7.80(d，J＝8.8Hz，2H)， 7.04(d，J＝8.8Hz，2H)，6.96(t，J＝2.8Hz，1H)，6.70(t，J＝2.7Hz，1H)，3.82(s，3H)，3.28(q，J＝ 5.2Hz，2H)，3.15(d，J＝4.1Hz，2H). 13 C NMR(100MHz，DMSO-d 6 )δ163.1，162.5，161.3，156.8， 129.74，127.2，126.0，123.1，122.1，114.2，107.6，55.3，37.6，31.4.HRMS(ESI)：calcd for C 16 H 17 N 4 O 2 [M+H] + 297.1346，found 297.1344.
Synthesis of I-8: the synthesis method is the same as I-2. Yellow solid, yield 87%, melting point 228-230 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.80(s，1H)，8.45-8.39(m，1H)，8.08(d，J＝5.7Hz，1H)，7.79(t，J＝7.3Hz， 2H)，7.07-7.00(m，2H)，6.99-6.91(m，1H)，4.10(dd，J＝7.4，3.9Hz，2H)，3.29(s，2H)，1.37(t，J ＝6.5Hz，3H). 13 C NMR(100MHz，DMSO-d 6 )δ163.6，163.0，161.1，157.3，130.3，127.5，126.5， 123.6，122.6，115.1，108.1，63.8，38.1，32.0，15.0.HRMS(ESI)：calcd for C 17 H 19 N 4 O 2 [M+H] + 311.1503，found 311.1504.
Synthesis of I-9: the synthesis method is the same as I-2. Yellow solid, yield 86%, melting point 223-225 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.79(s，1H)，8.41(s，1H)，8.07(t，J＝5.1Hz，1H)，7.78(d，J＝8.7Hz，2H)， 7.02(d，J＝8.7Hz，2H)，6.96(t，J＝2.8Hz，1H)，6.70(t，J＝2.7Hz，1H)，3.99(t，J＝6.5Hz，2H)， 3.28(q，J＝5.1Hz，2H)，3.18-3.09(m，2H)，1.76(p，J＝7.1Hz，2H)，0.99(t，J＝7.4Hz，3H). 13 C NMR(100MHz，DMSO-d 6 )δ163.6，163.0，161.3，157.3，130.2，127.5，126.5，123.6，122.6，115.2， 108.1，69.6，38.1，32.0，22.4，10.8.HRMS(ESI)：calcd for C 18 H 21 N 4 O 2 [M+H] + 325.1659，found 325.1660.
Synthesis of I-10: the synthesis method is the same as I-2. Yellow solid, yield 89%, melting point 206-208 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.79(s，1H)，8.41(s，1H)，8.07(t，J＝5.1Hz，1H)，7.78(d，J＝8.7Hz，2H)， 7.05-7.00(m，2H)，6.96(t，J＝2.8Hz，1H)，6.70(t，J＝2.7Hz，1H)，4.03(t，J＝6.5Hz，2H)，3.28 (q，J＝5.1Hz，2H)，3.14(d，J＝8.7Hz，2H)，1.77-1.67(m，2H)，1.50-1.40(m，2H)，0.94(t，J＝ 7.4Hz，3H). 13 C NMR(100MHz，DMSO-d 6 )δ163.1，162.5，160.8，156.8，129.7，127.0，126.04， 123.1，122.1，114.7，107.6，67.3，37.6，31.4，30.6，18.7，13.7.HRMS(ESI)：calcd for C 19 H 23 N 4 O 2 [M+H] + 339.1816，found 339.1819.
Synthesis of I-11: the synthesis method is the same as I-2. Yellow solid, yield 89%, melting point 116-118 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.80(s，1H)，8.41(s，1H)，8.08(t，J＝5.1Hz，1H)，7.77(d，J＝8.6Hz，2H)， 7.10-7.04(m，2H)，6.96(t，J＝2.8Hz，1H)，6.70(t，J＝2.7Hz，1H)，3.29(q，J＝5.2Hz，2H)，3.17 -3.07(m，2H)，1.35(s，9H). 13 C NMR(100MHz，DMSO-d 6 )δ163.1，162.6，157.6，156.5，129.1， 129.1，126.1，123.02，123.0，122.2，107.7，78.8，37.6，31.5，28.5.HRMS(ESI)：calcd for C 19 H 24 N 4 O 2 [M+H] + 339.1816，found 339.1817.
Synthesis of I-12: the synthesis method is the same as I-2. Pale yellow solid, yield 87%, melting point 182-184 ℃. 1 H NMR (400MHz，DMSO-d 6 )δ11.81(s，1H)，8.44(s，1H)，8.08(t，J＝5.2Hz，1H)，7.86(d，J＝8.7Hz， 2H)，7.48-7.41(m，2H)，7.21(t，J＝7.4Hz，1H)，7.09(t，J＝9.5Hz，4H)，6.97(t，J＝2.7Hz，1H)， 6.70(t，J＝2.7Hz，1H)，3.31-3.25(m，2H)，3.18-3.07(m，2H). 13 C NMR(100MHz，DMSO-d 6 ) δ163.0，162.8，159.0，156.2，155.7，130.2，123.0，129.6，126.2，124.1，122.9，122.2，119.3，118.2， 107.7，37.6，31.5.HRMS(ESI)：calcd for C 21 H 19 N 4 O 2 [M+H] + 359.1503，found 359.1502.
Synthesis of I-13: the synthesis method is the same as I-2. Yellow solid, yield 87%, melting point 194-196 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.84(s，1H)，8.37(s，1H)，8.10(t，J＝5.1Hz，1H)，7.03(d，J＝2.3Hz，2H)， 6.98(t，J＝2.7Hz，1H)，6.71(s，1H)，6.62(d，J＝2.3Hz，1H)，3.81(s，6H)，3.29(t，J＝5.2Hz，2H)， 3.18-3.09(m，2H). 13 C NMR(100MHz，DMSO-d 6 )δ163.0，162.9，160.6，156.6，136.5，126.3， 122.8，122.2，107.7，105.8，102.7，55.3，37.6，31.5.HRMS(ESI)：calcd for C 17 H 19 N 4 O 3 [M+H] + 327.1452，found 327.1451.
Synthesis of I-14: the synthesis method is the same as I-2. Yellow solid, yield 80%, melting point 215-217 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ11.86(s，1H)，9.63(s，1H)，9.02(dd，J＝4.2，1.8Hz，1H)，8.49(ddd，J＝15.2， 7.9，1.7Hz，2H)，8.16(dd，J＝8.2，1.5Hz，1H)，8.12(t，J＝5.0Hz，1H)，7.75(t，J＝7.7Hz，1H)， 7.65(dd，J＝8.3，4.1Hz，1H)，7.01(t，J＝2.8Hz，1H)，6.80(t，J＝2.6Hz，1H)，3.33(q，J＝5.2Hz， 2H)，3.23(d，J＝7.4Hz，2H). 13 C NMR(100MHz，DMSO-d 6 )δ163.2，163.0，153.8，150.6，145.7， 136.6，131.1，130.8，128.0，126.8，126.4，126.3，123.0，122.2，121.9，107.9，37.6，31.6.HRMS(ESI)： calcd for C 18 H 16 N 5 O[M+H] + 318.1349，found 318.1349.
Example 3: synthesis of Aldrisin derivative I-15.
Synthesis of I-15: compound a was first synthesized according to the method reported in the literature (bioorg. Med. Chem. Lett.2011, 21, 4306-4309); thereafter, A (1.27 g,5.00 mmol) was weighed into a 100mL round bottom flask, 45mL of absolute ethanol was added, and then hydrazine hydrate (981. Mu.L, 20.00 mmol) was added, and the reaction was heated under reflux for 6h, and TLC detection was complete. Pressurizing and desolventizing, then adding ethanol again, repeatedly pressurizing and desolventizing to obtain yellow solid 1.34g, and quantifying the yield, wherein the melting point is 178-179 ℃. 1 H NMR (400MHz，MeOD-d 4 )δ7.30-7.19(m，3H)，7.11-7.05(m，2H)，7.00(d，J＝2.7Hz，1H)，6.43(d， J＝2.8Hz，1H)，5.50(s，2H)，3.38-3.32(m，2H)，2.70-2.62(m，2H). 13 C NMR(100MHz， MeOD-d 4 )δ147.2，138.8，128.2，128.2，128.0，127.7，127.0，126.5，121.7，106.4，51.3，37.6，31.9. HRMS(ESI)：calcd for C 15 H 17 N 4 O[M+H] + 269.1397，found 269.1396.
Example 4: and (3) synthesizing Aldrisin derivatives I-16 to I-37.
Synthesis of I-16: i-15 (268 mg,1.00 mmol) was weighed into a 50mL round bottom flask, 25mL absolute ethanol was added, followed by benzaldehyde (159 mg,1.5 mmol) and reacted at room temperature for 4h, TLC detection was complete. Reduced pressure desolventizing, column chromatography separation (V Petroleum ether ∶V Acetic acid ethyl ester =2:1) to yield 292mg of pale yellow solid with a yield of 81%, melting point of 180-181 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ7.80(dd，J＝6.5，3.0Hz，2H)，7.45-7.38(m，3H)，7.29(t，J＝7.2Hz，2H)， 7.13(d，J＝7.1Hz，2H)，6.92(t，J＝6.0Hz，1H)，6.86(d，J＝2.8Hz，1H)，5.60(s，2H)，3.37(q，J＝ 5.9Hz，2H)，3.21-3.13(m，2H). 13 C NMR(100MHz，CDCl 3 -d)δ164.7，163.3，157.3，138.3， 134.7，130.8，128.7，128.6，128.3，128.0，127.5，127.1，126.4，124.3，107.9，52.4，38.5，34.1.HRMS (ESI)：calcd for C 22 H 21 N 4 O[M+H] + 357.1710，found 357.1707.
Synthesis of I-17: the synthesis method is the same as that of I-16. Pale yellow solid, yield 51%, melting point 131-133 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ7.56(s，1H)，7.28(dd，J＝14.3，7.0Hz，4H)，7.16-7.11(m，2H)，6.85(d，J ＝2.9Hz，1H)，6.75(d，J＝2.9Hz，1H)，5.60(s，2H)，3.34(q，J＝5.8Hz，2H)，3.04-2.94(m，2H)， 1.18(s，9H). 13 C NMR(100MHz，CDCl 3 -d)δ167.0，165.0，161.3，138.4，128.6，127.9，127.5， 127.1，126.4，124.0，107.7，52.2，38.4，35.2，33.9，27.4.HRMS(ESI)：calcd for C 20 H 25 N 4 O[M+H] + 337.2023，found 337.2017.
Synthesis of I-18: the synthesis method is the same as that of I-16. Pale yellow solid, yield 82%, melting point 189-190 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.40(s，1H)，7.73(d，J＝7.8Hz，2H)，7.34(t，J＝7.3Hz，2H)，7.26(d，J＝7.7Hz，3H)，7.17(d，J＝7.4Hz，2H)，6.91(d，J＝2.8Hz，1H)，6.86(d，J＝2.8Hz，1H)，6.32(s， 1H)，5.63(s，2H)，3.44(q，J＝5.8Hz，2H)，3.29-3.21(m，2H)，2.43(s，3H). 13 C NMR(100MHz， CDCl 3 -d)δ164.6，163.0，157.5，141.2，138.3，132.0，129.5，128.6，128.3，128.0，127.5，127.1，126.5， 124.2，107.9，52.3，38.5，34.1，21.6.HRMS(ESI)：calcd for C 23 H 23 N 4 O[M+H] + 371.1866，found 371.1867.
Synthesis of I-19: the synthesis method is the same as that of I-16. Pale yellow solid, yield 83%, melting point 162-163 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.39(s，1H)，7.67(s，1H)，7.62(d，J＝7.6Hz，1H)，7.39-7.32(m，3H)， 7.27(d，J＝3.7Hz，2H)，7.18(d，J＝7.4Hz，2H)，6.91(d，J＝2.7Hz，1H)，6.87(d，J＝2.8Hz，1H)， 6.69(dd，J＝15.5，7.1Hz，1H)，5.64(s，2H)，3.43(q，J＝5.7Hz，2H)，3.28-3.19(m，2H)，2.44(s， 3H). 13 C NMR(100MHz，CDCl 3 -d)δ164.8，163.2，157.5，138.4，138.4，134.7，131.6，128.8，128.6， 128.0，127.5，127.2，127.1，126.4，125.7，124.3，107.9，52.4，38.5，34.1，21.4.HRMS(ESI)：calcd for C 23 H 23 N 4 O[M+H] + 371.1866，found 371.1868.
Synthesis of I-20: the synthesis method is the same as that of I-16. Pale yellow solid, yield 82%, melting point 174-175 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.68(s，1H)，7.95(dd，J＝7.7，1.5Hz，1H)，7.33-7.29(m，1H)，7.29-7.24 (m，3H)，7.21(dd，J＝10.3，5.5Hz，2H)，7.13(d，J＝6.9Hz，2H)，7.08(d，J＝6.2Hz，1H)，6.86(d， J＝2.8Hz，1H)，6.83(d，J＝2.8Hz，1H)，5.59(s，2H)，3.37(q，J＝5.9Hz，2H)，3.21-3.12(m，2H)， 2.52(s，3H). 13 C NMR(100MHz，CDCl 3 -d)δ164.8，163.5，156.5，138.4，138.3，132.7，131.1， 130.4，128.7，128.0，128.0，127.5，127.1，126.4，126.1，124.4，107.9，52.3，38.5，34.4，20.1.HRMS (ESI)：calcd for C 23 H 23 N 4 O[M+H] + 371.1866，found 371.1868.
Synthesis of I-21: the synthesis method is the same as that of I-16. Pale yellow solid, yield 80%, melting point 176-177 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.42(s，1H)，7.93(d，J＝8.0Hz，2H)，7.70(d，J＝8.1Hz，2H)，7.33(t，J＝ 7.2Hz，2H)，7.26(d，J＝7.3Hz，1H)，7.20-7.15(m，2H)，6.91(d，J＝2.9Hz，1H)，6.85(t，J＝4.0 Hz，2H)，5.63(s，2H)，3.43(q，J＝5.8Hz，2H)，3.20(dd，J＝6.6，4.2Hz，2H). 13 C NMR(100MHz， CDCl 3 )δ164.6，164.0，155.7，138.2，138.0，132.1(q，J＝32.0Hz)，128.7，128.4，128.1，127.6， 127.1，126.1，125.65(q，J＝4.0Hz)，123.9(q，J＝271.0Hz)，124.5，108.0，52.4，38.4，34.1.HRMS (ESI)：calcd for C 23 H 20 F 3 N 4 O[M+H] + 425.1584，found 425.1578.
Synthesis of I-22: the synthesis method is the same as that of I-16. Pale yellow solid, yield 83%, melting point 205-207 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ10.24(s，1H)，8.71(s，1H)，7.81(d，J＝7.8Hz，1H)，7.42-7.38(m，2H)， 7.35-7.29(m，3H)，7.25-7.17(m，3H)，6.94(d，J＝2.9Hz，1H)，6.89(d，J＝2.8Hz，1H)，6.67(t， J＝2.7Hz，1H)，6.24(s，1H)，5.64(s，2H)，3.53(q，J＝5.9Hz，2H)，3.32-3.25(m，2H). 13 C NMR (100MHz，CDCl 3 -d)δ164.8，162.4，159.9，138.3，133.5，128.7，128.3，128.1，127.6，127.1，126.5， 126.4，124.9，124.3，124.2，119.7，117.8，108.1，102.8，52.3，38.5，34.6.HRMS(ESI)：calcd for C 24 H 22 N 5 O[M+H] + 396.1819，found 396.1817.
Synthesis of I-23: the synthesis method is the same as that of I-16. Pale yellow solid, yield 59%, melting point 163-165 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ9.72(s，1H)，8.98(dd，J＝4.2，1.8Hz，1H)，8.56(d，J＝1.1Hz，1H)，8.20 (dd，J＝8.3，1.7Hz，1H)，7.93(dd，J＝8.1，1.2Hz，1H)，7.64(t，J＝7.7Hz，1H)，7.46(dd，J＝8.3，4.2Hz，1H)，7.33(t，J＝7.2Hz，2H)，7.27(s，1H)，7.17(d，J＝7.0Hz，2H)，6.92(q，J＝2.8Hz，2H)， 6.49(t，J＝5.9Hz，1H)，5.64(s，2H)，3.44(td，J＝6.0，3.7Hz，2H)，3.31-3.22(m，2H). 13 C NMR (100MHz，CDCl 3 -d)δ164.6，162.3，154.4，150.2，146.6，138.3，136.2，132.1，130.3，128.6，128.3， 128.1，127.5，127.2，127.1，126.7，126.3，124.0，121.4，108.1，52.3，38.6，34.0.HRMS(ESI)：calcd for C 25 H 22 N 5 O[M+H] + 408.1819，found 408.1813.
Synthesis of I-24: the synthesis method is the same as that of I-16. Yellow solid, yield 78%, melting point 171-173 ℃. 1 H NMR(400 MHz，CDCl 3 -d)δ8.70-8.64(m，1H)，8.39(s，1H)，8.06(d，J＝8.0Hz，1H)，7.74(t，J＝7.6Hz， 1H)，7.30(t，J＝8.3Hz，4H)，7.14(d，J＝7.5Hz，2H)，6.91-6.82(m，3H)，5.60(s，2H)，3.39(q，J ＝5.8Hz，2H)，3.19-3.10(m，2H). 13 C NMR(100MHz，CDCl 3 -d)δ164.6，163.1，156.9，153.6， 149.8，138.2，136.4，128.6，128.1，127.5，127.1，126.1，124.6，124.4，121.7，108.1，52.4，38.4，34.1. HRMS(ESI)：calcd for C 21 H 20 N 5 O[M+H] + 358.1662，found 358.1662.
Synthesis of I-25: the synthesis method is the same as that of I-16. Yellow solid, 92% yield, melting point 1159-161 ℃. 1 H NMR (400MHz，DMSO-d 6 )δ8.40(s，1H)，8.17(tt，J＝5.9，3.2Hz，1H)，7.90(s，1H)，7.80(d，J＝7.2Hz， 1H)，7.56-7.48(m，2H)，7.35-7.30(m，2H)，7.27-7.19(m，2H)，7.13(d，J＝7.0Hz，2H)，6.67 (d，J＝2.8Hz，1H)，5.62(s，2H)，3.23(q，J＝5.7Hz，2H)，3.09-2.96(m，2H). 13 C NMR(100MHz， DMSO-d 6 )δ163.8，163.6，155.4，139.5，137.1，134.1，131.2，130.8，128.9，128.9，128.4，127.7， 127.6，127.2，125.5，125.2，107.6，51.5，37.8，34.3.HRMS(ESI)：calcd for C 22 H 20 ClN 4 O[M+H] + 391.1320，found 391.1320.
Synthesis of I-26: the synthesis method is the same as that of I-16. Pale yellow solid, yield 85%, melting point 173-175 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.36(s，1H)，7.74(d，J＝8.1Hz，2H)，7.45(d，J＝8.1Hz，2H)，7.30(t，J＝ 7.3Hz，2H)，7.23(d，J＝7.2Hz，1H)，7.14(d，J＝7.4Hz，2H)，6.85(dd，J＝19.7，2.8Hz，2H)，6.49 (t，J＝6.1Hz，1H)，5.60(s，2H)，3.40(q，J＝5.9Hz，2H)，3.25-3.14(m，2H)，1.34(s，9H). 13 C NMR(100MHz，CDCl 3 -d)δ164.8，163.0，157.2，154.3，138.4，132.0，128.6，128.1，128.0，127.5， 127.1，126.5，125.7，124.2，107.9，52.4，38.5，35.0，34.1，31.2.HRMS(ESI)：calcd for C 26 H 29 N 4 O [M+H] + 413.2336，found 413.2337.
Synthesis of I-27: the synthesis method is the same as that of I-16. Pale yellow solid, yield 83%Melting point 179-180 ℃. 1 H NMR (400MHz，DMSO-d 6 )δ8.64(s，1H)，8.19-8.10(m，2H)，7.58(d，J＝7.9Hz，1H)，7.52(t，J＝7.6 Hz，1H)，7.46(t，J＝7.5Hz，1H)，7.33(t，J＝7.5Hz，2H)，7.24(dd，J＝18.7，5.0Hz，2H)，7.13(d，J ＝7.4Hz，2H)，6.70(d，J＝2.8Hz，1H)，5.62(s，2H)，3.23(d，J＝5.3Hz，2H)，3.04(t，J＝5.3Hz， 2H). 13 C NMR(100MHz，DMSO-d 6 )δ164.3，163.6，152.7，139.5，134.4，132.7，131.9，130.5， 128.9，128.5，128.5，128.0，127.7，127.2，125.6，125.1，107.7，51.5，37.8，34.4.HRMS(ESI)：calcd for C 22 H 20 ClN 4 O[M+H] + 391.1320，found 391.1320.
Synthesis of I-28: the synthesis method is the same as that of I-16. Yellow solid, yield 84%, melting point 199-201 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ8.41(d，J＝1.5Hz，1H)，8.14(s，1H)，7.86(d，J＝8.6Hz，2H)，7.58-7.52(m， 2H)，7.35-7.29(m，2H)，7.27-7.22(m，1H)，7.20(d，J＝2.3Hz，1H)，7.12(d，J＝7.5Hz，2H)， 6.67(t，J＝2.1Hz，1H)，5.61(s，2H)，3.22(q，J＝5.7Hz，2H)，3.02(t，J＝5.4Hz，2H). 13 C NMR (100MHz，DMSO-d 6 )δ163.7，163.6，163.6，155.8，139.5，135.8，133.9，130.1，129.4，128.9，128.4， 127.6，127.2，125.4，125.3，107.6，51.5，37.8，34.3.HRMS(ESI)：calcd for C 22 H 20 ClN 4 O[M+H] + 391.1320，found 391.1320.
Synthesis of I-29: the synthesis method is the same as that of I-16. Pale yellow solid, yield 58%, melting point 144-145 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.09(s，1H)，7.60(d，J＝5.1Hz，1H)，7.41(d，J＝3.8Hz，1H)，7.37-7.29 (m，3H)，7.17(d，J＝7.7Hz，2H)，7.14-7.05(m，2H)，6.94(t，J＝2.7Hz，1H)，6.13(s，1H)，5.63(s， 2H)，3.42(q，J＝5.8Hz，2H)，3.07(s，2H). 13 C NMR(100MHz，CDCl 3 -d)δ164.7，160.6，145.6， 138.3，134.8，133.6，133.0，128.7，128.2，127.6，127.2，126.6，126.5，124.4，109.0，52.4，38.3，33.3. HRMS(ESI)：calcd for C 20 H 20 N 4 OS[M+H] + 363.1274，found 363.1273.
Synthesis of I-30: the synthesis method is the same as that of I-16. Yellow solid, yield 85%, melting point 170-172 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ8.36(s，1H)，8.10(t，J＝5.9Hz，1H)，7.79(d，J＝8.8Hz，2H)，7.31(t，J＝7.3 Hz，2H)，7.24(t，J＝7.3Hz，1H)，7.18(d，J＝2.8Hz，1H)，7.11(d，J＝7.1Hz，2H)，7.04(d，J＝8.8 Hz，2H)，6.64(d，J＝2.8Hz，1H)，5.59(s，2H)，3.82(s，3H)，3.21(q，J＝5.7Hz，2H)，3.08-2.99 (m，2H). 13 C NMR(100MHz，DMSO-d 6 )δ163.8，163.0，161.9，157.0，139.6，130.3，128.9，128.3， 127.6，127.6，127.2，125.6，125.2，114.8，107.4，55.8，51.5，37.9，34.2.HRMS(ESI)：calcd for C 23 H 23 N 4 O 2 [M+H] + 387.1816，found 387.1817.
Synthesis of I-31: the synthesis method is the same as that of I-16. Yellow solid, yield 84%, melting point 163-164 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ8.37(s，1H)，8.12(t，J＝5.9Hz，1H)，7.79(d，J＝8.4Hz，2H)，7.32(t，J＝7.4 Hz，2H)，7.25(t，J＝7.3Hz，1H)，7.20(d，J＝2.9Hz，1H)，7.12(d，J＝7.5Hz，2H)，7.03(d，J＝8.4 Hz，2H)，5.61(s，2H)，4.10(q，J＝6.9Hz，2H)，3.22(q，J＝5.5Hz，2H)，3.04(t，J＝5.3Hz，2H)， 1.36(t，J＝7.0Hz，3H). 13 C NMR(100MHz，DMSO-d 6 )δ163.2，162.5，160.7，156.5，139.1，129.8， 128.4，127.8，127.1，127.0，126.7，125.1，124.6，114.6，107.0，63.3，51.0，37.4，33.7，14.5.HRMS (ESI)：calcd for C 24 H 25 N 4 O 2 [M+H] + 401.1972，found 401.1972.
Synthesis of I-32: the synthesis method is the same as that of I-16. Yellow solid, yield 82%, melting point 145-147 ℃. 1 H NMR(400 MHz，CDCl 3 -d)δ8.36(s，1H)，7.74(d，J＝8.7Hz，2H)，7.30(t，J＝7.2Hz，2H)，7.24(d，J＝7.4Hz， 1H)，7.14(d，J＝7.0Hz，2H)，6.93(d，J＝8.7Hz，2H)，6.88(d，J＝2.9Hz，1H)，6.83(d，J＝2.9Hz， 1H)，6.19(t，J＝6.1Hz，1H)，5.60(s，2H)，3.97(t，J＝6.6Hz，2H)，3.42(q，J＝5.9Hz，2H)，3.23 (dd，J＝6.5，4.2Hz，2H)，1.83(q，J＝7.0Hz，2H)，1.05(t，J＝7.4Hz，3H). 13 C NMR(101MHz， CDCl 3 -d)δ164.8，162.9，161.4，157.3，138.4，129.9，128.6，128.0，127.5，127.3，127.1，126.6，124.2， 114.7，107.8，69.6，52.3，38.5，34.1，22.5，10.5.HRMS(ESI)：calcd for C 25 H 27 N 4 O 2 [M+H] + 415.2129，found 415.2130.
Synthesis of I-33: the synthesis method is the same as that of I-16. Yellow solid, yield 85%, melting point 145-147 ℃. 1 H NMR(400 MHz，CDCl 3 -d)δ8.39(s，1H)，7.77(d，J＝8.4Hz，2H)，7.34(t，J＝7.3Hz，2H)，7.27(d，J＝7.4Hz， 1H)，7.18(d，J＝7.4Hz，2H)，6.96(d，J＝8.4Hz，2H)，6.91(d，J＝2.8Hz，1H)，6.86(d，J＝2.9Hz， 1H)，6.30(t，J＝6.2Hz，1H)，5.64(s，2H)，4.04(t，J＝6.5Hz，2H)，3.44(q，J＝5.8Hz，2H)，3.29- 3.18(m，2H)，1.82(dd，J＝8.5，6.2Hz，2H)，1.54(q，J＝7.5Hz，2H)，1.02(t，J＝7.4Hz，3H). 13 C NMR(100MHz，CDCl 3 -d)δ164.8，162.9，161.4，157.3，138.4，129.9，128.6，128.0，127.5，127.3， 127.1，126.6，124.2，114.7，107.8，67.8，52.3，38.5，34.1，31.2，19.2，13.9.HRMS(ESI)：calcd for C 26 H 29 N 4 O 2 [M+H] + 429.2285，found 429.2287.
Synthesis of I-34: the synthesis method is the same as that of I-16. Yellow solid, yield 86%, melting point 151-153 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ8.36(s，1H)，8.11(t，J＝5.9Hz，1H)，7.76(d，J＝8.6Hz，2H)，7.31(t，J＝7.3 Hz，2H)，7.24(t，J＝7.3Hz，1H)，7.19(d，J＝2.8Hz，1H)，7.09(dd，J＝15.8，7.9Hz，4H)，6.65(d， J＝2.8Hz，1H)，5.60(s，2H)，3.21(q，J＝5.7Hz，2H)，3.09-2.98(m，2H)，1.35(s，9H). 13 C NMR (100MHz，DMSO-d 6 )δ163.2，162.6，157.7，156.1，139.1，129.1，129.0，128.4，127.8，127.1，126.7， 125.0，124.7，123.0，107.0，78.8，51.0，37.4，33.8，28.5.HRMS(ESI)：calcd for C 26 H 29 N 4 O 2 [M+H] + 429.2285，found 429.2288.
Synthesis of I-35: the synthesis method is the same as that of I-16. Yellow solid, yield 79%, melting point 160-162 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ8.39(s，1H)，8.11(t，J＝5.9Hz，1H)，7.90-7.81(m，2H)，7.49-7.41(m，2H)， 7.31(t，J＝7.3Hz，2H)，7.24(dd，J＝12.8，7.3Hz，2H)，7.19(d，J＝2.7Hz，1H)，7.15-7.03(m， 6H)，6.65(d，J＝2.8Hz，1H)，5.60(s，2H)，3.21(q，J＝5.8Hz，2H)，3.06-2.95(m，2H). 13 C NMR (100MHz，DMSO-d 6 )δ163.7，163.2，159.5，156.3，156.2，139.55，130.7，130.5，130.0，128.9， 128.4，127.6，127.2，125.5，125.2，124.6，119.8，118.7，107.5，51.5，37.9，34.3.HRMS(ESI)：calcd for C 28 H 25 N 4 O 2 [M+H] + 449.1972，found 449.1974.
Synthesis of I-36: the synthesis method is the same as that of I-16. White solid, yield 83%, melting point 164-165 ℃. 1 H NMR(400 MHz，DMSO-d 6 )δ8.30(s，1H)，8.12(t，J＝5.9Hz，1H)，7.32(t，J＝7.3Hz，2H)，7.24(t，J＝7.3Hz， 1H)，7.20(d，J＝2.8Hz，1H)，7.11(d，J＝7.1Hz，2H)，7.01(d，J＝2.3Hz，2H)，6.64(d，J＝2.8Hz， 1H)，6.61(t，J＝2.2Hz，1H)，5.60(s，2H)，3.79(s，6H)，3.21(q，J＝6.1，5.7Hz，2H)，3.05-2.95(m， 2H). 13 C NMR(100MHz，DMSO-d 6 )δ163.1，162.7，160.6，156.1，139.0，136.4，128.4，127.9， 127.2，126.7，124.9，124.8，107.0，105.8，102.8，55.3，51.0，37.4，33.7.HRMS(ESI)：calcd for C 24 H 25 N 4 O 3 [M+H] + 417.1921，found 417.1923.
Synthesis of I-37: the synthesis method is the same as that of I-16. Pale yellow solid, yield 50%, melting point 202-204 ℃. 1 H NMR (400MHz，CDCl 3 -d)δ8.36(s，1H)，7.64(d，J＝1.9Hz，2H)，7.34-7.29(m，2H)，7.27(s，1H)， 7.15(d，J＝6.9Hz，2H)，6.89(d，J＝2.8Hz，1H)，6.84(s，1H)，6.08(t，J＝6.1Hz，1H)，5.61(s，2H)， 3.43(q，J＝6.0Hz，2H)，3.20(dd，J＝6.6，4.3Hz，2H)，1.36(s，18H). 13 C NMR(100MHz， CDCl 3 -d)δ164.6，162.4，158.0，151.2，138.3，134.0，128.6，128.0，127.5，127.1，126.5，125.2，124.1， 122.6，107.9，52.3，38.6，34.9，34.0，31.4.HRMS(ESI)：calcd for C 30 H 37 N 4 O[M+H] + 469.2962， found 469.2958.
Example 5: the tobacco mosaic virus resistance activity was measured as follows:
1. virus purification and concentration determination:
the virus purification and concentration measurement are carried out by compiling tobacco mosaic virus SOP standard according to a measuring room generated by elements of university of south China. After 2 times of polyethylene glycol centrifugation treatment, the concentration of the virus crude extract is measured, and the virus crude extract is refrigerated at 4 ℃ for standby.
2. Compound solution preparation:
weighing, adding DMF to dissolve the compound and ribavirin to obtain 1×10 5 Mu g/mL mother liquor, and then diluting the mother liquor to the required concentration by using an aqueous solution containing 1 per mill of Tween 80.
3. Living body protecting action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole plant is sprayed and applied, each treatment is repeated for 3 times, and 1 permillage of Tween 80 aqueous solution is used for comparison. After 24h, the leaf surface is spread with silicon carbide (500 meshes), the whole leaf surface is dipped with a virus liquid by a writing brush, the whole leaf surface is lightly rubbed for 2 times along the branch pulse direction, the lower part of the leaf surface is supported by a palm, the virus concentration is 10 mug/mL, and the leaf surface is washed by running water after inoculation. And after 3d, recording the number of the lesions, and calculating the control effect.
4. In vivo therapeutic action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole leaf of the writing brush is inoculated with virus, the virus concentration is 10 mug/mL, and the whole leaf is washed by running water after inoculation. After leaf surface is dried, spraying and applying the whole plant, repeating for 3 times every treatment, and setting 1%Tween 80 water solution as a control. And after 3d, recording the number of the lesions, and calculating the control effect.
TABLE 1 results of Tobacco Mosaic Virus (TMV) resistance Activity test of Aldrisin derivatives
5. In vivo passivation:
selecting 3-5 She Qishan Xie smoke with uniform growth vigor, mixing the medicament with an equal volume of virus juice, inactivating for 30min, performing friction inoculation, wherein the virus concentration is 20 mug/mL, washing with running water after inoculation, repeating for 3 times, and setting 1 milltween 80 water solution for comparison. And counting the number of lesions after 3d, and calculating a result.
Inhibition ratio (%) = [ (control number of dried spots-treated number of dried spots)/control number of dried spots ] ×100%
Firstly, performing in-vivo deactivation activity test of all compounds at a treatment dose of 500 mug/mL, and performing in-vivo treatment and activity protection activity test of the compounds with relative inhibition rate of more than 40% at the treatment dose of 500 mug/mL. The positive control is ribavirin which is a commercial anti-plant virus agent.
As can be seen from the data in Table 1, at 500. Mu.g/mL, some derivatives of the alkaloid Aldrisin exhibited good anti-TMV activity, with the anti-TMV activity of compound I-19 being comparable to that of commercial ribavirin, while compounds I-3, I-4, I-20, I-23 and I-24 had anti-TMV activity superior to that of ribavirin.
Example 6: the insecticidal activity was tested and the procedure was as follows:
TABLE 2 insecticidal Activity test results of Aldrisin derivatives against armyworms and cotton bollworms
Myxoplasma: the test method is a leaf dipping method. Soaking corn leaf in the medicinal liquid prepared from acetone for 5-6 s, taking out, drying, inoculating 10 heads of 3-year-old myxoworm larva, mainly stomach poisoning, killing by touch, and observing larva feeding phenomenon. Mortality was checked after 72 hours.
Plutella xylostella larvae, cotton bollworms and corn borers and armyworms are the same method. Each compound was tested twice (three times for the plutella xylostella corresponding compound) and averaged.
Mosquito larvae: the culex spinosa is a light subspecies, and is a normal group for indoor feeding. 10 heads of 3-year-old culex larvae are selected and placed in a 100mL beaker filled with experimental liquid with required concentration. It was placed in a standard treatment chamber and after 72 hours the mortality was checked, and each compound was tested twice and averaged. An aqueous solution containing 1mL of the test solvent was used as a blank.
Mortality (%) = [ (number of control insects-number of surviving insects)/number of control insects ] ×100%
Table 3 results of test of insecticidal Activity of Aldrisin derivatives against corn borer and Plutella xylostella
As can be seen from the data in Table 2, most of the Aldrisin derivatives exhibited insecticidal activity against armyworms and cotton bollworms, with compounds I-1, I-3, I-4, I-6, I-14-I-15, I-17-I-20, I-25 and I-32 having excellent insecticidal activity against armyworms.
As can be seen from the data in Table 3, most of the Aldrisin derivatives showed insecticidal activity against corn borers and plutella xylostella at 600. Mu.g/mL, wherein the compounds I-6, I-7, I-9, I-15, I-19, I-24, I-27 to I-29, I-31, I-36 and I-37 had excellent insecticidal activity against plutella xylostella.
Table 4 results of test for insecticidal Activity of Aldrisin derivatives against mosquito larvae
As can be seen from the data in Table 4, most of the Aldrisin derivatives had insecticidal activity against mosquito larvae at 10. Mu.g/mL, with compounds I-1, I-3 to I-6, I-16 to I-18 and I-22 having excellent insecticidal activity against mosquito larvae.
Example 7: antibacterial activity was tested, and the assay procedure was as follows:
cell growth rate assay (plate method): the test compound was dissolved with acetone, and 200. Mu.g/mL of an aqueous emulsifier solution was added to prepare a test solution of the desired concentration. 1mL of the solution to be tested is sucked into a culture dish, 9mL of culture medium is added, the mixture is stirred uniformly to prepare a 50 mug/mL drug-containing plate, and a plate with 1mL of sterilized water is prepared as a blank control. The trays were cut along the outer edge of the mycelium with a punch of 4mm diameter and transferred to the drug-containing plate and the control plate. The same operation was repeated 3 times. Finally, the dishes were placed in a thermostatic incubator, after 48 hours, the colony diameters were measured, and the average of 3 measurements was compared with the blank control, and the relative inhibition ratio was calculated.
Relative inhibition (%) = [ (control colony diameter-test colony diameter)/control colony diameter ] ×100%
Table 5 results of in vitro bactericidal Activity test of Aldrisin derivatives
As can be seen from the data in Table 5, under the condition of 50 mug/mL, aldrisin derivatives I-1 to I-37 show broad-spectrum inhibition activity on 14 tested bacteria, wherein the inhibition rates of the compound I-6 on the gibberella capsici, the sclerotium of the rape and the apple ring rot are 78+2%, 80+/-1% and 76+/-2%, respectively; the inhibitory activity of the compound I-21 on the wheat sheath blight is 74+/-2%; the inhibition activity of the compound I-25 on the sclerotium of the rape is 71+/-2%; the inhibition activity of the compound I-30 on the gibberella wheat is 73+/-2%; the inhibitory activity of the compound I-31 on the wheat sheath blight is 79+/-2%; the inhibitory activity of the compound I-32 on phytophthora capsici and colza sclerotium is 70+/-2% and 65+/-1% respectively; the inhibition activities of the compound I-33 on the sclerotium of the rape and the banded sclerotial blight of the wheat are 65+/-2% and 86+/-1% respectively.
Claims (10)
1. An Aldisin derivative containing a hydrazone structure, which is a compound shown in a general formula I:
wherein R represents hydrogen, substituted or unsubstituted benzyl; the substituents of the substituted benzyl are each independently selected from one or more of hydroxy, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbyl, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene;
R 1 、R 2 respectively represent hydrogen or R 1 、R 2 Is combined into
R 3 Represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted quinolinyl group, a substituted or unsubstituted indolyl group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted thienyl group; the substituents of the substituted phenyl, the substituted quinolinyl, the substituted indolyl, the substituted pyridinyl and the substituted thiophenyl are each independently selected from one or more of halogen, C1-C6 alkyl, C1-C6 alkoxy and phenoxy.
2. An Aldisin derivative containing a hydrazone structure according to claim 1, R represents hydrogen, substituted or unsubstituted benzyl; the substituent of the substituted benzyl is independently selected from one or more of hydroxyl, F, cl, br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy and n-pentoxy;
R 1 、R 2 respectively represent hydrogen or R 1 、R 2 Is combined into
R 3 Represents substituted or unsubstituted phenyl, substituted or unsubstituted quinolinyl, substituted or unsubstituted indolyl, substituted or unsubstitutedPyridyl, substituted or unsubstituted thienyl; the substituents of the substituted phenyl, substituted quinolinyl, substituted indolyl, substituted pyridinyl, substituted thiophenyl are each independently selected from one or more of F, cl, br, I, cyano, nitro, trifluoromethyl, trifluoromethoxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, phenoxy.
3. The Aldisin derivative containing a hydrazone structure according to claim 1 or 2, wherein the compound is one of the compounds represented by the following formula:
4. a process for the preparation of an Aldisin derivative containing a hydrazone structure according to any one of claims 1 to 3, which comprises, in a first process: taking Aldrisin as a raw material, taking ethanol as a solvent, and carrying out condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain the hydrazone-containing derivative
5. A process for the preparation of an Aldisin derivative containing a hydrazone structure according to any one of claims 1 to 3, which comprises, in a second process: taking Aldisin as a raw material, taking ethanol as a solvent, and carrying out condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain a hydrazone-containing derivative; ethanol is used as solvent, and the reaction of addition elimination is carried out with aromatic aldehyde under the room temperature condition, thus obtaining hydrazone with diimine structure
6. A process for the preparation of an Aldisin derivative containing a hydrazone structure according to any one of claims 1 to 3, which comprises, in a third process: aldrisin and benzyl bromide are used as reactants, sodium carbonate is used as alkali, acetonitrile is used as a solvent, and a compound A is obtained under the condition of heating and refluxing; taking a compound A as a raw material, taking ethanol as a solvent, and carrying out condensation reaction with hydrazine hydrate under the condition of heating reflux to obtain the hydrazone derivative protected on pyrrole nitrogen
7. A process for the preparation of an Aldisin derivative containing a hydrazone structure according to any one of claims 1 to 3, which comprises, a process four: the hydrazone derivative protected on pyrrole nitrogen is taken as a raw material, ethanol is taken as a solvent, and an addition elimination reaction is carried out with aromatic aldehyde under the room temperature condition, so as to obtain the hydrazone of the diimine structure of the hydrazone derivative protected on pyrrole nitrogen
8. Use of Aldisin derivatives containing hydrazone structures according to any one of claims 1 to 3 for the treatment of plant virus diseases, characterized in that said series of derivatives have activity for the control of tobacco mosaic virus.
9. Use of Aldisin derivatives containing hydrazone structures according to any one of claims 1 to 3 for insecticidal purposes, characterized in that the series of derivatives have insecticidal activity against one or more of armyworms, cotton bollworms, corn borers, plutella xylostella and mosquito larvae.
10. Use of Aldisin derivatives containing hydrazone structures according to any one of claims 1 to 3 for sterilization, characterized in that said series of derivatives have inhibitory activity against one or more of cucumber wilt, peanut brown spot, apple ring spot, wheat sharp eyespot, corn small spot, watermelon anthrax, rice bakanae, tomato early blight, wheat gibberella, rice blast, phytophthora capsici, rape sclerotium, cucumber gray mold and rice sharp eyespot.
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