A pyrrolo[3,4-c]quinoline compound, a synthetic method and application thereof

Abstract

The application provides a pyrrolo[3,4- c ]quinoline compound, a synthesis method and application thereof. The application takes o-amino-nitrostyrene and allene acid ester as raw materials, and through one-pot multi-step cascade reaction under the action of an organic phosphine catalyst and the mediation of zinc / acetic acid, a series of pyrrolo[3,4- c ]quinoline compounds with a full-carbon quaternary carbon center are obtained. Advantages of the application include: the reaction reagent is cheap and easy to obtain, the reaction is rapid and efficient, the reaction steps are short, the application is economical and practical, and the application is environment-friendly; the reaction is easy to scale up and has practical value. The compound represented by formula (III) has good inhibitory activity on Geotrichum candidum and Rhizoctonia solani, and the effect of the compound 3 is the best, reaching 89% and 88% respectively.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology and its application, specifically relating to a pyrrolo[3,4- c Quinoline compounds, their synthesis methods and applications. Background Technology

[0002] Pyrrole [3,4- c Quinoline compounds possess unique structures, with their core skeletons widely found in natural products and drugs. For example, a novel pentacyclic aromatic alkaloid, plakinidine B, was isolated from the Plakortis sponge. This fused aromatic ring system is a structural variation not previously observed in aromatic alkaloids from marine or terrestrial sources. Plakinidine B exhibits in vitro activity against *Lactobacillus brasiliensis*. Alpkinidine extracted from the sponge's natural product also showed good cytotoxicity against mouse tumor cells. This class of pyrrolo[3,4- c The structure of quinoline exhibits excellent inhibitory activity against caspase-3. Furthermore, various compounds containing pyrrolo[3,4-] have also been discovered. c Natural compounds with the quinoline skeleton have significant and novel biological activities.

[0003]

[0004] Contains pyrrolo[3,4- c Drugs and active molecules with a quinoline skeleton Developing pyrrolo[3,4- c The synthetic strategy for the quinoline core structure has always been a topic of great interest in organic synthesis; however, organocatalytic strategies for synthesizing this framework are rarely reported. The goal of this invention is to design a simple and practical catalytic method to prepare this framework. Therefore, this invention utilizes pyrrolo[3,4- c The quinoline core structure was split into o-aminonitrostyrene and allenoate, and pyrrolo[3,4-] was constructed via phosphine catalysis. c Quinoline nucleus structure. Summary of the Invention

[0005] This invention innovatively provides a method for efficiently constructing a hexa-5-membered ring skeleton of pyrroloquinoline. The inventors discovered that o-aminonitrostyrene is a unique class of nitrogen-substituted benzene ring compounds, characterized by stability and ease of preparation. Therefore, this invention designs a reaction method for preparing pyrrolo[3,4-c]quinoline hexa-5-membered ring compounds by reacting o-aminonitrostyrene with acetoxyisopropionate.

[0006] This invention proposes a method for synthesizing pyrrole[3,4-c]quinoline hexacyclic five-membered ring compounds. Under the catalytic conditions of an organophosphorus catalyst, o-aminonitrostyrene and acetoxyisopropionate are used as reactants in a reaction solvent, effectively achieving the corresponding transformation to prepare pyrrole[3,4-c]quinoline as shown in formula (III). c Quinoline hexacyclic five-membered ring compounds. The reaction process is shown in the following reaction formula (a):

[0007] Among them, R 1 It is an alkyl or aryl group; R 2 It is an alkyl or aryl group; R 3 It is an alkyl or aryl group.

[0008] Preferably, R 1 Selected from ethyl, tert-butyl, benzyl, 2-methylbenzyl, 2-fluorobenzyl, diphenylmethyl, naphthylbenzyl, phenethyl, fluorenyl; R 2 Selected from methyl, phenyl, 4-methylphenyl, 4-methoxybenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2-bromophenyl, 3-bromophenyl, naphthyl; R 3 Selected from hydrogen, methyl, methoxy, bromine, and chlorine atoms.

[0009] As shown in reaction formula (a) above, this invention utilizes o-aminonitrostyrene as shown in formula (I) and allenoate as shown in formula (II) as reaction raw materials, and reacts in a reaction solvent under the action of an organophosphorus catalyst and the mediation of zinc / acetic acid to obtain pyrrolo[3,4-] as shown in formula (III). c Quinoline compounds.

[0010] In this invention, the catalyst is triphenylphosphine, diphenylethylphosphine, phenyldiethylphosphine, tributylphosphine, or tris(dimethylamino)phosphine. Preferably, the catalyst is tris(dimethylamino)phosphine.

[0011] In this invention, the alkali is cesium carbonate, sodium carbonate, potassium carbonate, sodium tert-butoxide, potassium tert-butoxide, or triethylamine. Preferably, the alkali is cesium carbonate.

[0012] In this invention, the solvent is acetonitrile, benzonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, or acetone. Preferably, the solvent is acetonitrile.

[0013] In this invention, the ratio of the starting material, o-aminonitrostyrene as shown in formula (I), to the allene ester as shown in formula (II), is 1:1 to 1:2. Preferably, the ratio is 1:1.5.

[0014] In this invention, the reaction temperature is 20-30℃; preferably, the temperature is 25℃.

[0015] The synthetic reaction of this invention includes the following steps: The reaction described in formula (a) comprises the following steps: adding o-aminonitrostyrene of formula (I), allenate of formula (II), cesium carbonate, acetonitrile, and organophosphorus catalyst to a reaction vessel, and reacting at 25°C. o After stirring the reaction under C conditions, zinc powder and acetic acid are added, and the mixture is refluxed to obtain pyrrolo[3,4-] as shown in formula (III). c Quinoline compounds.

[0016] In a specific example, such as reaction (a), the synthesis reaction of the present invention involves adding o-aminonitrostyrene (X mmol), allenoate (Y mmol), base (Z mmol), solvent (V mL), and organophosphorus catalyst (P mmol) to reaction flask A. The reaction system is then heated to 25 °C. o Stirring at C for 1 hour; then adding zinc powder (m mmol) and acetic acid (n mmol), and stirring the reaction system under reflux for 3 hours; after the reaction is complete, the reaction system is cooled to room temperature, concentrated, neutralized, and separated by column chromatography to obtain the target product.

[0017] The present invention also proposes a pyrrolo[3,4-] ... c Quinoline compounds,

[0018] Among them, R 1 It is ethyl, tert-butyl, benzyl, 2-methylbenzyl, 2-fluorobenzyl, diphenylmethyl, naphthylbenzyl, phenethyl, fluorenyl; R 2 It is methyl, phenyl, 4-methylphenyl, 4-methoxybenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2-bromophenyl, 3-bromophenyl, naphthyl; R 3 It can be any one of hydrogen, methyl, methoxy, bromine, or chlorine atoms.

[0019] The present invention also proposes pyrrolo[3,4-] as shown in formula (III) above. c Quinoline compounds are synthesized in the presence of pyrrolo[3,4-] c Application methods of potential drugs with quinoline core skeleton.

[0020] Another technical solution of the present invention is to use the pyrrolo[3,4- c Application of quinoline compounds in inhibiting Geotrichum candida and / or Rhizoctonia solani.

[0021] Another technical solution of the present invention is to use the pyrrolo[3,4-c Application of quinoline compounds in the preparation of drugs that inhibit Geotrichum candida and / or Rhizoctonia solani.

[0022] The present invention has the following advantages: (1) the reaction reagents are inexpensive and readily available; (2) the reaction is fast and efficient; (3) the reaction steps are short, economical and practical, and environmentally friendly; (4) the reaction is easy to scale up and has practical value.

[0023] This invention uses o-aminonitrostyrene and allenolate as reactants, and obtains a series of pyrrolo[3,4-c]quinoline compounds with all-carbon and quaternary carbon centers through a one-pot, multi-step tandem reaction under the action of an organophosphorus catalyst and mediated by zinc / acetic acid. The advantages of this invention include: inexpensive and readily available reagents; rapid and efficient reaction; short reaction steps; economical and practical; environmentally friendly; and high reaction efficiency after scale-up, making it practically valuable. Attached Figure Description

[0024] Figure 1 This is the hydrogen spectrum of compound 1.

[0025] Figure 2 This is the carbon spectrum of compound 1.

[0026] Figure 3 This is the hydrogen spectrum of compound 5.

[0027] Figure 4 This is the carbon spectrum of compound 5.

[0028] Figure 5 This is the hydrogen spectrum of compound 8.

[0029] Figure 6 This is the carbon spectrum of compound 8.

[0030] Figure 7 This is the proton NMR spectrum of compound 10.

[0031] Figure 8 This is the carbon spectrum of compound 10. Detailed Implementation

[0032] The present invention will be further described in detail below with reference to specific embodiments. However, the scope of protection of the present invention is not limited to these embodiments. All variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention and are protected by the appended claims. The processes, conditions, reagents, experimental methods, etc., used to implement the present invention, except as specifically mentioned below, are all common knowledge and general knowledge in the art, and the present invention does not have any particular limitations. The data given in the following embodiments include specific operations, reaction conditions, and products. Product purity was determined by NMR.

[0033] This invention pyrrolo[3,4-c The synthesis reaction of quinoline compounds includes the following steps: As shown in equation a: o-aminonitrostyrene, acetoxyisopropionate, cesium carbonate, acetonitrile, and organophosphorus catalyst were added to a reaction vessel and stirred at 25°C; then zinc powder and acetic acid were added, and the mixture was refluxed to obtain pyrrolo[3,4-] as shown in equation (III). c Quinoline compounds. The product was then concentrated, neutralized, and separated by column chromatography. Conditions were screened during the process, as shown in the table below:

[0034]

[0035] As shown in Table 1, pyrrolo[3,4-] c The quinoline compounds are all products synthesized by the method of this invention, and no published literature has disclosed these compounds.

[0036]

[0037] Example 1

[0038] o-Aminonitrostyrene (31.8 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube. Then, benzyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.) was added, followed by the organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%). The reaction was carried out at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 62%; 1 H NMR (400 MHz, CDCl3) d 7.72 – 7.67 (m, 2H), 7.46 (d, J = 8.4 Hz,1H), 7.41 – 7.31 (m, 5H), 7.27 – 7.25 (m, 2H), 7.13 – 7.02 (m, 3H), 5.20 (d, J = 12.0 Hz, 1H), 5.16 (d,J = 12.0 Hz, 1H), 4.57 (d, J = 13.7 Hz, 1H), 4.41 (m,1H), 3.94 (dd, J = 9.3, 5.4 Hz, 1H), 3.77 (d, J = 13.7 Hz, 1H), 3.40 – 3.32 (m,1H), 2.39 (s, 3H), 2.10 (t, J = 2.4 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d 170.5,170.0, 144.0, 137.4, 137.1, 134.9, 132.5, 129.7, 129.2, 128.71, 128.67,128.4, 127.3, 127.1, 125.1, 120.8, 69.9, 68.8, 67.7, 48.1, 43.9, 21.5,16.6.HRMS (ESI)m / z: calcd. for C 27 H 27 N2O4S + (M + H) + 475.1686, found 475.1672. Example 2

[0039] o-Aminonitrostyrene (31.8 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube. Then, o-methylbenzoate acetoxyisopropionate (39.0 mg, 0.15 mmol, 1.5 equiv.) was added, followed by the organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%). The reaction was carried out at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product 2 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 56%; 1 H NMR (400 MHz, CDCl3) d 7.69 (d, J= 8.3 Hz, 2H), 7.47 (d, J =8.1 Hz, 1H), 7.28 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 2.6 Hz, 2H), 7.20 (d, J = 7.4Hz, 2H), 7.13 – 7.01 (m, 3H), 5.23 (d, J = 12.3 Hz, 14H), 5.18 (d, J = 12.3 Hz,1H), 4.59 (d, J = 13.7 Hz, 1H), 4.44 – 4.34 (m, 1H), 3.93 (dd, J = 9.4, 5.4 Hz,1H), 3.74 (d, J = 13.7 Hz, 1H), 3.34 (m, 1H), 2.39 (s, 3H), 2.34 (s, 3H), 2.10(t, J = 2.0 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl3) d 170.6, 170.1, 144.0, 137.4,137.04, 137.02, 132.9, 132.5, 130.5, 129.7, 129.5, 129.1, 129.0, 127.3,127.1, 126.1, 125.1, 120.8, 70.0, 68.9, 66.1, 48.1, 44.0, 21.5, 18.9,16.5.HRMS (ESI)m / z: calcd. for C 28 H 29 N2O4S + (M + H) + 489.1843, found 489.1849. Example 3

[0040] o-Aminonitrostyrene (39.6 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube. Then, 2-F benzoyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.) was added. Next, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the reaction was carried out at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 57%; 1 H NMR (400 MHz, CDCl3) d 7.74 – 7.66 (m, 2H), 7.49 – 7.41 (m,1H), 7.40 – 7.30 (m, 2H), 7.27 (m, 2H), 7.18 – 7.02 (m, 5H), 5.25 (t, J = 13.2Hz, 2H), 4.57 (d, J = 13.7 Hz, 1H), 4.45 – 4.34 (m, 1H), 3.95 (dd, J = 9.4, 5.4Hz, 1H), 3.76 (d, J = 13.7 Hz, 1H), 3.42 – 3.30 (m, 1H), 2.39 (s, 3H), 2.13 (t, J = 2.0 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d 170.4, 170.1, 161.1 ( J = 247.6 Hz),144.0, 137.4, 137.1, 132.4, 130.9 ( J = 2.8 Hz), 130.8 ( J = 1.8 Hz), 129.7,129.2, 127.3, 127.1, 125.1, 124.3 ( J = 3.7 Hz), 122.1 ( J = 14.3 Hz), 120.8, 115.7 ( J= 20.8 Hz), 69.9, 68.8, 61.78, 48.1, 43.9, 21.5, 16.5. 19 F{ 1 H NMR (100MHz, CDCl3) d -117.5.HRMS (ESI)m / z: calcd. for C 27 H 26 FN2O4S + (M + H) + 493.1592, found 493.1602. Example 4

[0041] Anthranilyl nitrosyl (31.8 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube. Then, 2-phenylmethyl acetoxyisopropionate (48.3 mg, 0.15 mmol, 1.5 equiv.) was added. Next, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the mixture was reacted at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product 4 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 53%; 1 H NMR (400 MHz, CDCl3) d 7.73 – 7.66 (m, 2H), 7.51 – 7.47 (m,1H), 7.38 – 7.27 (m, 10H), 7.24 (d, J = 8.2 Hz, 2H), 7.10 (m, 1H), 7.08 – 7.01(m, 2H), 6.90 (s, 1H), 4.71 (d, J = 13.7 Hz, 1H), 4.52 – 4.42 (m, 1H), 3.91(dd, J = 9.3, 5.0 Hz, 1H), 3.72 (d, J = 13.7 Hz, 1H), 3.40 (m, 1H), 2.38 (s, 3H), 2.05 (t, J = 2.4 Hz, 3H).13 C{ 1 H NMR (100 MHz, CDCl3) d 170.2, 169.7, 144.0,139.19, 139.16, 137.5, 136.9, 132.6, 129.7, 129.2, 128.71, 128.67, 128.33,128.28, 127.3, 127.12, 127.05, 126.9, 125.1, 120.9, 78.4, 70.2, 69.1, 48.0,44.2, 21.5, 16.6.HRMS (ESI)m / z: calcd. for C 33 H 31 N2O4S + (M + H) + 551.1999, found 551.1993. Example 5

[0042] o-Aminonitrostyrene (31.8 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube, followed by ethyl acetoxyisopropionate (27.6 mg, 0.15 mmol, 1.5 equiv.). Then, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the mixture was reacted at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 55%; 1 H NMR (400 MHz, CDCl3) d 7.76 – 7.66 (m, 2H), 7.51 – 7.42 (m, 1H),7.27 (d, J = 7.7 Hz, 2H), 7.15 – 7.00 (m, 3H), 4.55 (d, J = 13.6 Hz, 1H), 4.42(m, 1H), 4.27 – 4.19 (m, 2H), 3.95 (dd, J = 9.4, 5.5 Hz, 1H), 3.77 (d, J= 13.6Hz, 1H), 3.42 – 3.33 (m, 1H), 2.39 (s, 3H), 2.20 (t, J = 2.0 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d 170.6, 170.5, 144.0, 137.4, 137.1,132.4, 129.8, 129.2, 127.3, 127.0, 125.0, 120.7, 69.8, 68.7, 62.1, 48.1,43.9, 21.5, 16.6, 14.1.HRMS (ESI)m / z: calcd. for C 22 H 24 N2NaO6S + (M + Na) + 435.1349, found 435.1349. Example 6

[0043] Benzenesulfonated o-aminonitrostyrene (30.4 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube, followed by benzyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.). Then, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the reaction was carried out at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product 6 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 56%; 1 H NMR (400 MHz, Chloroform- d ) d 7.85 – 7.78 (m, 2H), 7.58 –7.53 (m, 1H), 7.47 (m, 3H), 7.41 – 7.29 (m, 5H), 7.15 – 7.04 (m, 3H), 5.23 –5.14 (m, 2H), 4.58 (d, J= 13.8 Hz, 1H), 4.46 – 4.36 (m, 1H), 3.95 (dd, J = 9.4, 5.4 Hz, 1H), 3.79 (d, J = 13.8 Hz, 1H), 3.34 (m, 1H), 2.09 (t, J = 2.0 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) d 170.5, 169.9, 140.2, 137.3, 134.9, 133.1,132.6, 129.2, 129.1, 128.72, 128.68, 128.4, 127.2, 127.1, 125.3, 121.0, 70.0,68.8, 67.7, 48.2, 44.0, 16.6.HRMS (ESI)m / z: calcd. for C 26 H 25 N2O4S + (M + H) + 461.1530, found 461.1526. Example 7

[0044] 4-Methoxybenzenesulfonated o-aminonitrostyrene (33.4 mg, 0.1 mmol, 1.0 equiv.) and the reaction solvent acetonitrile (1.0 mL), along with Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.), were added to a reaction tube, followed by benzyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.). Then, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the mixture was reacted at 25 °C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product 7 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 44%; 1 H NMR (400 MHz, CDCl3) d 7.78 – 7.71 (m, 2H), 7.49 (dd, J= 8.1, 1.1 Hz, 1H), 7.43 – 7.28 (m, 5H), 7.07 (m, 3H), 6.95 – 6.88 (m, 2H), 5.19 (d, J = 12.1 Hz, 1H), 5.17 (d, J = 12.1 Hz, 1H), 4.58 (d, J = 13.7 Hz, 1H), 4.41 (m, 1H), 3.94 (dd, J = 9.4, 5.4 Hz, 1H), 3.83 (s, 3H), 3.75 (d, J = 13.7 Hz,1H), 3.39 – 3.31 (m, 1H), 2.11 (t, J = 2.0 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d 170.5, 170.2, 163.2, 137.5, 134.9, 132.5, 131.3, 129.6, 129.1, 128.71,128.66, 128.3, 127.0, 125.0, 120.8, 114.2, 70.0, 68.9, 67.7, 55.6, 47.9,43.9, 16.6.HRMS (ESI)m / z: calcd. for C 27 H 26 N2NaO6S + (M + Na) + 513.1455, found 513.1459. Example 8

[0045] Trimethylbenzenesulfonate o-aminonitrostyrene (34.6 mg, 0.1 mmol, 1.0 equiv.), acetonitrile (1.0 mL) as the reaction solvent, and Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.) as the Cs₂CO₃ were added to a reaction tube, followed by benzyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.). Then, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the mixture was reacted at 25°C. oThe mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 66%; 1 H NMR (400 MHz, CDCl3) d 7.35 (d, J = 3.6 Hz, 5H), 7.17 –7.13 (m, 1H), 7.08 (td, J = 7.4, 1.2 Hz, 1H), 7.03 – 6.96 (m, 3H), 6.62 (dd, J =8.1, 1.2 Hz, 1H), 5.20 (d, J = 12.1 Hz, 1H), 5.17 (d, J = 12.1 Hz, 1H), 4.52 (m,1H), 4.38 (d, J = 14.3 Hz, 1H), 4.03 (dd, J = 9.7, 6.0 Hz, 1H), 3.90 – 3.79 (m,2H), 2.53 (s, 6H), 2.34 (s, 3H), 1.96 (d, J = 2.0 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d 170.9, 169.9 143.0, 139.8, 137.7, 135.4, 135.0, 133.8, 132.3, 129.3,128.7, 128.6, 128.4, 127.1, 125.8, 121.9, 69.8, 68.9, 67.6, 48.3, 43.9, 22.8,21.0, 16.4.HRMS (ESI)m / z: calcd. for C 29 H 30 N2NaO4S + (M + Na) + 525.1818, found 525.1809. Example 9

[0046] 5-Methyl-o-aminonitrostyrene (33.2 mg, 0.1 mmol, 1.0 equiv.), acetonitrile (1.0 mL) as the reaction solvent, and Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.) were added to a reaction tube, followed by benzyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.). Then, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the mixture was reacted at 25°C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product 9 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 53%; 1 H NMR (400 MHz, CDCl3) d 7.68 (d, J = 8.3 Hz, 2H), 7.42 – 7.28(m, 6H), 7.24 (d, J = 8.5 Hz, 2H), 6.95 – 6.86 (m, 2H), 5.20 (d, J = 12.2 Hz, 1H), 5.18 (d, J = 12.2 Hz, 1H), 4.55 (d, J = 13.7 Hz, 1H), 4.43 – 4.34 (m, 1H), 3.89 (dd, J = 9.4, 5.5 Hz, 1H), 3.75 (d, J = 13.7 Hz, 1H), 3.38 – 3.28 (m, 1H), 2.38 (s, 3H), 2.25 (s, 3H), 2.10 (t, J = 2.0 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d 170.6, 170.1, 143.9, 137.2, 134.9, 134.81, 134.75, 132.3, 129.66,129.62, 128.7, 128.6, 128.3, 127.7, 127.3, 120.8, 69.9, 68.7, 67.6, 48.1,43.9, 21.5, 20.7, 16.6.HRMS (ESI)m / z: calcd. for C28 H 28 N2NaO4S + (M + Na) + 511.1662, found 511.1671. Example 10

[0047] 5-Methyl-o-aminonitrostyrene (34.8 mg, 0.1 mmol, 1.0 equiv.), acetonitrile (1.0 mL) as the reaction solvent, and Cs₂CO₃ (39.2 mg, 0.12 mmol, 1.2 equiv.) were added to a reaction tube, followed by benzyl acetoxyisopropionate (36.9 mg, 0.15 mmol, 1.5 equiv.). Then, organophosphorus catalyst (NMe₂)₃P (3.3 mg, 20 mol%) was added, and the mixture was reacted at 25°C. o The mixture was stirred at temperature C for 1 hour, then Zn powder and AcOH were added, and the mixture was refluxed for 3 hours. The reaction solution was then neutralized, the solvent was removed under reduced pressure, and the product 10 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 3:1). Yield: 51%; 1 H NMR (400 MHz, CDCl3) d 7.64 (d, J = 8.3 Hz, 2H), 7.47 – 7.28(m, 6H), 7.23 (d, J = 8.0 Hz, 2H), 6.71 – 6.56 (m, 2H), 5.19 (d, J = 12.1 Hz, 1H), 5.15 (d, J = 12.1 Hz, 1H), 4.57 (d, J = 14.0 Hz, 1H), 4.42 – 4.32 (m, 1H), 3.89 (dd, J = 9.5, 5.6 Hz, 1H), 3.73 (m, 4H), 3.34 – 3.22 (m, 1H), 2.38 (s,3H), 2.09 (t, J = 2.0 Hz, 3H). 13 C{ 1 H NMR (100 MHz, CDCl3) d170.6, 170.1, 156.9,143.9, 137.2, 134.9, 134.3, 130.2, 129.6, 128.71, 128.67, 128.3, 127.3,122.7, 114.1, 112.4, 69.7, 68.9, 67.7, 55.4, 48.4, 44.2, 21.5, 16.5.HRMS(ESI)m / z: calcd. for C 28 H 29 N2O5S + (M + H) + 505.1792, found 505.1791. Example 11 Antibacterial activity test: The concentration of the compound was 30 ppm. Using a punch (5 mm), inoculate the bacterial culture onto a PDA medium containing the test compound, mycelial side down, in the center of a circular medium. Three samples were inoculated for each test sample. The blank control group consisted of medium containing the same concentration of DMSO but without the test compound. After incubation at 25°C for 3–5 days in a biochemical incubator, the diameter of the colonies on the medium was measured. The effect of the test sample on mycelial growth was observed by comparing it with the blank control group. The inhibition rate of the test sample on colony growth at 30 μg / mL was calculated. Inhibition rate (%) = [(Blank control colony diameter - Test sample colony diameter) / (Blank colony diameter - Punch diameter)] × 100%.

[0048] The table below shows the determination of some compounds:

[0049] As can be seen from the table above, among compounds 1, 3, 5, 8, and 10, compound 3 showed the best effect, achieving antibacterial efficacy of 89% and 88% against *Gnaphalium affine* and *Rhizoctonia solani*, respectively. Other compounds also exhibited significant antibacterial effects. In the embodiments described above, compounds 2 and 4 are structurally similar to compound 3; compounds 6 and 7 are structurally similar to compound 8; and compound 9 is structurally similar to compound 10. Therefore, those skilled in the art could predict that compounds with similar structures would have significant antibacterial effects against *Gnaphalium affine* and *Rhizoctonia solani*.

Claims

1. A pyrrolo[3,4- c Quinoline compounds, characterized in that, The structure is shown in equation (Ⅲ): Among them, R 1 It is selected from any one of ethyl, tert-butyl, benzyl, 2-methylbenzyl, 2-fluorobenzyl, diphenylmethyl, and phenethyl; R 2 It is selected from any one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 2,4,6-trimethylphenyl, 2-bromophenyl, 3-bromophenyl, and naphthyl; R 3 It is selected from any one of hydrogen, methyl, methoxy, bromine, and chlorine atoms.

2. The pyrrolo[3,4-] according to claim 1 c A method for synthesizing quinoline compounds, characterized in that, Using formulas (I) and (II) as reactants, and under the catalysis of a catalyst and the mediation of zinc / acetic acid, a reaction was carried out in a reaction solvent to obtain pyrrolo[3,4-] as shown in formula (III). c Quinoline compounds; the reaction process is shown in reaction formula (a); Among them, R 1 It is selected from any one of ethyl, tert-butyl, benzyl, 2-methylbenzyl, 2-fluorobenzyl, diphenylmethyl, and phenethyl; R 2 It is selected from any one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 2,4,6-trimethylphenyl, 2-bromophenyl, 3-bromophenyl, and naphthyl; R 3 It is selected from any one of hydrogen, methyl, methoxy, bromine, and chlorine atoms; The catalyst is triphenylphosphine, diphenylethylphosphine, phenyldiethylphosphine, or tri(dimethylamino)phosphine; the base is cesium carbonate, sodium carbonate, potassium carbonate, sodium tert-butoxide, potassium tert-butoxide, or triethylamine; and the solvent is acetonitrile, benzonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, or acetone.

3. The synthesis method as described in claim 2, characterized in that, The ratio of the amounts of formula (I) and formula (II) in the raw materials of the reaction is 1:1 to 1:

2.

4. The synthesis method according to claim 2, characterized in that, The reaction temperature is 20-30℃.

5. The pyrrolo[3,4-] as described in claim 1 c The use of quinoline compounds in the inhibition of Geotrichum candida and / or Rhizoctonia solani, excluding the diagnosis and treatment of diseases.

6. The pyrrolo[3,4-] ... c The use of quinoline compounds in the preparation of drugs that inhibit Geotrichum candida and / or Rhizoctonia solani, excluding the diagnosis and treatment of diseases.

Images