Novel N-acyltetrahydroisoquinoline compounds and their use as fungicides against plant pathogenic fungi

Abstract

The present invention relates to the fields of pesticides and plant protection. Specifically, it relates to novel N-acyltetrahydroisoquinoline compounds, including their stereoisomers, prodrug molecules, and pharmaceutically acceptable salts, and their use in the preparation of anti-plant pathogenic fungicides. The structure of these isoquinoline compounds is shown in Formula (I): #imgabs0#. The compounds described herein have significant inhibitory activity against various plant pathogenic fungi and can be used to prepare fungicides.

Description

Technical Field

[0001] The present invention relates to the fields of pesticides and plant protection, in particular to N-acyl tetrahydroisoquinoline compounds and applications thereof in preparing anti-plant pathogenic fungicides. Background Art

[0002] Plant pathogenic fungi are a major contributor to crop yield and quality decline. Furthermore, during their infestation, pathogenic fungi can secrete a variety of toxins and metabolites that are harmful to humans and animals, posing a threat to agricultural product safety. Chemical fungicides are the most effective method for controlling plant pathogenic fungal infections. However, in recent years, the long-term and irrational use of chemical fungicides has led to increasing problems such as high residues, drug resistance, and environmental pollution. Therefore, there is an urgent need to develop green fungicides with novel modes of action and environmental friendliness to control plant fungal diseases and safeguard food security.

[0003] Tetrahydroisoquinoline alkaloids are important members of the alkaloid family, widely distributed in plants such as the Magnoliaceae, Aristolochiaceae, Berberidaceae, and Papaveraceae families. They possess a variety of biological activities, including antifungal, antiviral, antitumor, and antimalarial activities, and their development and application have attracted considerable attention from pharmaceutical researchers. The active nucleus of tetrahydroisoquinoline alkaloids is the tetrahydroisoquinoline (THIQ) fragment, which is present in a variety of drug molecules and pesticide chemicals. Previously, the applicant reported the invention of two classes of 3-arylisoquinoline compounds, using the quaternary ammonium isoquinoline alkaloids: sanguinarine, chelerythrine, and berberine, as the lead compounds, and their use as anti-plant pathogenic fungicides. This work demonstrated that the isoquinoline structure is a potential antibacterial nucleus, laying the experimental foundation for the development of natural anti-plant pathogenic fungicides (CN 115353488 B).

[0004] Based on previous research results, the applicants used tetrahydroisoquinoline alkaloids with antibacterial activity as leads. Using a biomimetic design strategy, they simplified the lead structure and, incorporating the principle of pharmacophore splicing, designed and synthesized a series of novel N-acyltetrahydroisoquinoline derivatives. The results demonstrated that the novel N-acyltetrahydroisoquinoline derivatives described in this invention exhibit antibacterial activity against a variety of plant pathogenic fungi.

[0005] The novel N-acyl tetrahydroisoquinoline compounds involved in the present invention are all new compounds that have not been reported in the literature. This patent is the first report by the applicant on the anti-plant pathogenic fungal activity of this type of N-acyl tetrahydroisoquinoline derivatives. Summary of the Invention

[0006] The present invention aims to provide novel N-acyltetrahydroisoquinoline compounds and their use in preparing anti-plant pathogenic fungicides.

[0007] The novel N-acyl tetrahydroisoquinoline compounds of the present invention have a general structural formula as shown in Formula (I):

[0008]

[0009] In formula (I), R1-R4 are selected from hydrogen, halogen, hydroxy, trifluoromethyl, C1-C6 alkyl and C1-C6 alkoxy.

[0010] In formula (I), Ar is selected from aromatic groups such as benzene ring, naphthalene ring, biphenyl ring, thiophene ring, furan ring, pyrazole ring, thiazole ring, pyridine ring, etc., and the specific structure is shown in formula (II).

[0011]

[0012] In formula (II), R5 is selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C1-C6 straight-chain or branched alkyl and C1-C6 straight-chain or branched alkoxy; or two adjacent R5 together with the carbon atoms on the aromatic ring to which they are connected form a five-membered or six-membered aliphatic ring or aliphatic oxygen heterocycle; and n is an integer of 1-5.

[0013] The present invention provides a general preparation method for the novel N-acyl tetrahydroisoquinoline compound I, and its typical synthetic route is as follows:

[0014]

[0015] Compound I is used as a fungicide for the preparation of anti-plant pathogenic fungi. Biological activity tests show that the target compound has significant inhibitory activity against wheat sheath blight (Rhizotonia cerealis), rice sheath blight (Rhizoctonia solani), wheat head blight (Fusarium graminearum), corn leaf blight (Helminthosporium maydis), rapeseed sclerotinia (Sclerotinia sclerotiorum), tomato early blight (Alternaria solani), apple ring rot (Physalospora piricola), cucumber gray mold (Botrytis cinerea), and pear black spot (Alternaria alternata).

[0016] Compared with the prior art, the present invention has the following advantages and effects:

[0017] This invention uses natural antibacterial active ingredients such as rugenine, chrysotoxine, and scoparine as lead compounds. Using a biomimetic design strategy, with a unified biomimetic skeleton of tetrahydroisoquinoline as the parent core, key pharmacophores from amides, succinate dehydrogenase inhibitors, and biphenyl fungicides were introduced to design and synthesize a series of novel N-acyltetrahydroisoquinoline compounds. In vitro antimicrobial activity tests demonstrated significant activity against plant pathogenic fungi. Some target compounds were comparable to the commercial fungicides chlorothalonil and boscalid, providing fundamental data for the synthesis of N-acyltetrahydroisoquinoline derivatives and broader bioactivity studies. DETAILED DESCRIPTION

[0018] In the present invention, the novel N-acyl tetrahydroisoquinoline compounds designed and synthesized by the applicant have the following general structural formula:

[0019]

[0020] In formula (I), R1-R4 are selected from hydrogen, halogen, hydroxy, trifluoromethyl, C1-C6 alkyl and C1-C6 alkoxy.

[0021] In formula (I), Ar is selected from aromatic groups such as benzene ring, naphthalene ring, biphenyl ring, thiophene ring, furan ring, pyrazole ring, thiazole ring, pyridine ring, etc., and the specific structure is shown in formula (II).

[0022]

[0023] In formula (II), R5 is selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C1-C6 straight-chain or branched alkyl and C1-C6 straight-chain or branched alkoxy; or two adjacent R5 together with the carbon atoms on the aromatic ring to which they are connected form a five-membered or six-membered aliphatic ring or aliphatic oxygen heterocycle; and n is an integer of 1-5.

[0024] Novel N-acyltetrahydroisoquinoline compounds are used as fungicides against plant pathogenic fungi. It is known that isoquinoline compounds have significant inhibitory activity against the following common plant pathogenic fungi: wheat sheath blight (Rhizotonia cerealis; RC), rice sheath blight (Rhizoctonia solani; RS), wheat head blight (Fusarium graminearum; FG), corn leaf blight (Helminthosporium maydis; HM), rapeseed sclerotinia (Sclerotinia sclerotiorum; SS), tomato early blight (Alternaria solani; AS), apple ring rot (Physalospora piricola; PP), cucumber gray mold (Botrytis cinerea; BC), and pear black spot (Alternaria alternata; AA).

[0025] The general synthesis method of the N-acyltetrahydroisoquinoline compound I of the present invention is shown in Reaction Scheme 1, and is specifically illustrated using Compound I-1.

[0026]

[0027] Example 1, Synthesis of Compound I-1.

[0028] The synthetic route of compound I-1 is shown in Reaction Scheme 2.

[0029]

[0030] Synthesis of Intermediate 4a: Dissolve 3,4-dimethoxyphenylethylamine (1.81 g, 10 mmol, 1.0 eq.) and p-fluorobenzaldehyde (1.48 g, 12 mmol, 1.2 eq.) in 20 mL of anhydrous toluene. Heat the mixture and monitor the reaction by thin-layer chromatography (TLC) until completion. Cool the mixture to room temperature, add 10 mL of trifluoroacetic acid, and heat under reflux. Monitor the reaction by TLC until completion. Quench the reaction by adding water, adjust the pH to a weak base with sodium hydroxide, and wash with saturated brine (15 mL x 3). The organic phase is collected, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and isolated by column chromatography (DCM:MeOH) to afford 4a.

[0031] Synthesis of target compound I-1: Dissolve difluoropyrazole acid (0.17 g, 1 mmol, 1.0 eq.) in 15 mL of dichloromethane, slowly add oxalyl chloride (0.19 g, 1.5 mmol, 1.5 eq.), then add 1-2 drops of DMF. Stir and react for 3 h. Monitor by TLC until the reaction is complete. Concentrate under reduced pressure to obtain the crude acyl chloride for later use. Add 4a (0.29 g, 1 mmol, 1.0 eq.) and triethylamine (0.12 g, 1.2 mmol, 1.2 eq.) to 10 mL of dichloromethane, cool in an ice bath, and dissolve the crude acyl chloride in dry dichloromethane (5 mL). Add the solution dropwise slowly and uniformly using a constant pressure funnel and allow to react overnight. Monitor by TLC until the reaction is complete, then add dichloromethane (40 mL) and wash with saturated brine (15 mL x 3). The organic phase was collected, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography (PE:EA) to obtain the target compound I-1.

[0032] Compound I-1: white powder, yield 93%. 1 H NMR (600MHz, CDCl3) δ7.51(s,1H),7.29(dt,J=8.3,6.0Hz,1H),7.13(d,J=7.8Hz,1H),7.02–6.94(m,3H),6.67(s,1H),6.55(s,1H),3.98(s,3H ),3.91(s,3H),3.80(s,3H),3.64(dd,J=14.7,5.9Hz,1H),3.32(t,J=12.5Hz,1H),2.88(s,1H),2.69(dd,J=16.1,4.2Hz,1H).HRMS(ESI)calcd for C 23 H 23 F3N3O3[M+H] + 446.1692, found 446.1713.

[0033] The synthesis methods of the remaining target compounds I are the same as I-1.

[0034] According to the preparation method of Example 1, a series of derivatives I-1 to I-21 were obtained, and their structures are shown in Table 1.

[0035] Table 1 Structural formula of series target compound I

[0036]

[0037]

[0038]

[0039] The physicochemical data of some representative compounds are as follows:

[0040] Compound I-2: white powder, yield 95%. 1 H NMR (600MHz, CDCl3) δ7.47–7.43(m,1H),7.31–7.24(m,2H),7.09–7.01(m,4H),6.91(s,1H),6.70(s,1H),6.55(s,1H),4.35(s,1H),3.90(s,3H),6 3.77(s,3H),3.58(s,1H),3.02(ddd,J=17.1,10.8,6.0Hz,1H),2.81(dt,J=16.4,3.9Hz,1H). 13 C

[0041] NMR(100MHz,CDCl3)δ163.71,160.84(d, 1 J CF =249.3Hz),148.51,147.

[0042] 98,137.58,130.83,129.56(129.47),129.25(129.12),128.56,128.52,126.57,126.44,123.79(123.76),116.01(115.79),111.49,110.84,56.02,55.96,53.20,41.06,28.65.

[0043] Compound I-3: white powder, yield 96%, mp 89–91 °C. 1 H NMR (600MHz, CDCl3) δ7.51(s,1H),7.30–7.24(m,1H),7.11(d,J=7.9Hz,1H),6.97(td,J=8.3,3.1Hz,3H),6.66(s,1H),6.53(s,1H),3. 96(s,3H),3.89(s,3H),3.78(s,3H),3.63(dd,J=13.7,5.9Hz,1H),3.31(td,J=14.8,13.7,8.7Hz,1H),2.87(s,1H),2.72–2.66(m,1H). 13 C NMR(150MHz,CDCl3)δ162.71(d, 1 J CF =254.0Hz),161.92,148.47,147.89,144.47,138.91(d, 2 J CF=39.1Hz),130.20,129.85(129.80),125.96,125.39,124.52,120.67(q, 1 J CF =269.5Hz),116.10,115.84(115.69),114.75(114.61),111.19,111.10,55.99,55.90,54.36,40.85,39.71,28.52.

[0044] Compound I-4: white powder, yield 94%, mp 94–96 °C. 1 H NMR(400MHz, CDCl3)δ7.48(dd,J=5.0,1.1Hz,1H),7.35(dd,J=3.7,1.2Hz,1H),7.07–7.05(m,5H),4.32–4.16(m,1H), 3.92(s,3H),3.80(s,3H),3.45–3.35(m,1H),3.11(ddd,J=17.3,11.7,6.0Hz,1H),2.78(ddd,J=16.3,4.5,2.3Hz,1H).

[0045] Compound I-5: white powder, yield 89%. 1 H NMR (600MHz, CDCl3) δ7.86–7.82(m,2H),7.46–7.42(m,2H),7.25(t,J=7.6Hz,1H),7.17(t,J=7.5Hz,1H),7.06–7.02(m,2H),7.00(s ,1H),6.67(s,1H),6.53(s,1H),3.94(s,3H),3.90(s,3H),3.77(q,J=6.5,Hz,3H),2.89(s,1H),2.73(s,1H),2.47(t,J=6.5,Hz,2H).

[0046] Compound I-6: white powder, yield 90%. 1H NMR (600MHz, CDCl3) δ7.46(dd,J=5.0,1.2Hz,1H),7.44(d,J=8.0Hz,1H),7.31(s,1H),7.24(td,J=7.7,1.7Hz,2H),7.16(td,J=7.6,1.4Hz ,1H),7.04–6.98(s,3H),6.92(dd,J=7.8,1.7Hz,1H),6.68(s,1H),6.56(s,1H),4.33(s,1H),3.47(s,1H),2.97(s,1H),2.78–2.72(m,1H). 13 C NMR (100MHz, CDCl3) δ164.40,148.58,148.08,139.71,137.56,134.58,131.13,130.14,128.90,128.67,126.62,126.57,126.42,120.67(q, 1 J CF =269.5Hz),111.56,110.96,28.86.

[0047] Compound I-7: white powder, yield 96%. 1 H NMR (600MHz, CDCl3) δ7.48–7.42(m,5H),7.14–7.09(m,3H),6.97–6.84(m,4H),6.66(s,1H),6.48(s,1H),3.89(s,3H),3.76(s,3H) ,3.62(dd,J=14.0,6.0Hz,1H),3.44(ddd,J=13.9,11.9,4.5Hz,1H),2.92(ddd,J=17.5,11.8,6.3Hz,1H),2.77(s,1H),2.75(s,3H). 13 C NMR (150MHz, CDCl3) δ167.69,159.23,148.54,148.13,140.74,139.30,138.74,134.45,132.38,131.17,130.15,129 .21,128.15,127.21,127.16,126.95,126.62,126.56,125.95,125.62,111.19,110.69,55.91,53.82,41.93,19.10.

[0048] Compound I-8: white powder, yield 93%. 1H NMR (400MHz, CDCl3) δ7.47(8.05)(s,1H),7.42(d,J=2.2Hz,1H),7.11(dd,J=8.3,2.2Hz ,1H),6.87(6.97)(s,1H),6.85(6.83)(s,1H),6.77(dd,J=55.1,54.0Hz,1H),6.65(s,1H ),6.47(s,1H),3.95(s,1H),3.90(s,3H),3.85(s,3H),3.73(s,3H),3.38(td,J=14.1,13 .4,4.2Hz,1H),2.87(ddd,J=17.0,11.2,5.8Hz,1H),2.70(ddd,J=16.3,4.6,2.3Hz,1H).

[0049] Compound I-9: white powder, yield 95%. 1 H NMR (400MHz, CDCl3) δ7.47(d,J=1.2Hz,1H),7.38(d,J=77.8Hz,1H),7.32(d,J=3.6Hz,1H), 7.15(ddd,J=8.3,2.1,1.2Hz,1H),7.05(ddd,J=4.9,3.6,1.2Hz,1H),6.90(s,1H),6.90–6. 86(m,1H),6.68(s,1H),4.34(dd,J=14.9,6.0Hz,1H),3.90(d,J=1.2Hz,3H),3.79(d,J=1.2 Hz, 3H), 3.46 (q, J=8.5, 4.3Hz, 1H), 2.97 (ddd, J=17.4, 11.6, 6.3Hz, 1H), 2.79–2.71 (m, 1H).

[0050] Compound I-10: white powder, yield 89%. 1 H NMR (400MHz, CDCl3) δ7.54(s,1H),7.47(s,1H),7.18–7.11(m,1H),7.01(s,1H),6.87(s,1H),6.66(s,1H),6.48(s,1H ),3.97(s,3H),3.89(s,3H),3.76(s,3H),3.81–3.71(m,1H),3.46–3.34(m,1H),2.86(s,1H),2.72(d,J=14.1Hz,1H).

[0051] Compound I-11: white powder, yield 93%. 1H NMR (400MHz, CDCl3) δ7.50(d,J=2.3Hz,1H),7.16(dd,J=8.4,2.1Hz,1H),6.98(s,1H),6.86(d,J=8.4Hz,1H),6.67(s,1H),6.49(s,1H),3 .90(s,3H),3.78(s,3H),3.64(dd,J=14.0,6.0Hz,1H),3.51–3.39(m,1H),2.94(ddd,J=17.6,11.6,6.2Hz,1H),2.77(s,3H),2.74(s,1H). 13 C NMR (150MHz, CDCl3) δ167.80,159.36,148.67,148.26,139.96(d, 2 J CF =36.6Hz),137.52,135.16,134.45,132.14,131.95,129.95,126.90,125.58,125. 46,123.74–116.65(m),111.25,110.48,55.94,55.92,53.39,41.99,28.57,19.12.

[0052] Compound I-12: white powder, yield 96%. 1 H NMR (600MHz, CDCl3) δ7.51(s,1H),6.91(d,J=45.0Hz,2H),6.81(t,J=54.1Hz,1H),6.68(s,1H),6.50(s,1H),3.96(d,J=2.6H z,3H),3.93–3.88(m,3H),3.83(s,1H),3.81(d,J=2.1Hz,3H),3.30(s,1H),2.92(s,1H),2.71(ddd,J=16.1,4.5,2.1Hz,1H). 13 C NMR (150MHz, CDCl3) δ162.85,151.84,150.19,148.77,148.03,143.88,140.05 ,138.39,130.09,126.23,124.67,115.18,112.96,111.35,110.95,110.46(t, 1 J CF =236.0Hz),56.03,55.94,53.90,41.03,39.49,28.51.

[0053] Compound I-13: white powder, yield 95%.1 H NMR(400MHz, CDCl3)δ7.48(7.28)(s,1H),7.47–7.45(m,1H),7.32(d,J=3.6Hz,1H),7 .15(dt,J=8.3,1.7Hz,1H),7.05(ddd,J=4.9,3.6,1.2Hz,1H),6.92–6.85(m,2H),6.68 (s,1H),6.52(s,1H),4.34(dd,J=14.8,6.0Hz,1H),3.90(d,J=1.2Hz,3H),3.79(d,J=1 .2Hz,3H),3.52–3.42(m,1H),2.97(ddd,J=17.4,11.5,6.2Hz,1H),2.79–2.71(m,1H).

[0054] Compound I-14: white powder, yield 92%. 1 H NMR (600MHz, CDCl3) δ7.52(s,1H),6.94(t,J=7.0Hz,2H),6.88(s,1H),6.67(s,1H),6.48(s,1H),3.98(s,3H),3.90(s,3H),3.80(s,3H ), 3.66(dd,J=13.7,5.9Hz,1H), 3.26(td,J=13.1,4.1Hz,1H), 2.87(ddd,J=17.6,12.2,5.9Hz,1H), 2.69(ddd,J=16.4,4.5,2.0Hz,1H). 13 CNMR(150MHz, CDCl3)δ162.09,151.86,150.13,148.79,148.11,140.15,138.28,130.18,126.04,124.38,120.63(d, 1 J CF =269.8Hz),115.83,113.04,112.92,111.28,110.91,56.02,55.94,53.79,40.83,39.77,28.41.

[0055] Compound I-15: white powder, yield 91%. 1H NMR (600MHz, CDCl3) δ6.97–6.92(m,1H),6.83(s,1H),6.67(s,1H),6.47(s,0H),3.89(s,2H),3.78(s,2H),3.52(ddt,J=13.9,6.1,1. 5Hz,1H),3.31(ddd,J=13.9,12.3,4.3Hz,1H),2.91(ddd,J=16.2,12.2,6.1Hz,1H),2.76(s,3H),2.71(ddd,J=16.5,4.4,1.6Hz,1H). 13 C NMR (150MHz, CDCl3) δ167.92,159.63,151.89(151.83),150.22(150.17),148.91,148.23,139.77(d, 2 J CF =36.8Hz),140.56–138.29(m),137.64,131.64–131.18(m),125.78,123.83,120.08(q, 1 J CF =271.9Hz),113.18(113.15),113.06(113.04),111.25,110.74,55.99,55.91,54.31,40.86,28.20,19.08.

[0056] Compound I-16: white powder, yield 87%. 1 H NMR (600MHz, CDCl3) δ7.58(d,J=3.2Hz,1H),7.49(d,J=6.2Hz,1H),7.42(s,1 H),7.37(s,1H),7.31(d,J=5.4Hz,2H),7.21(td,J=4.3,2.1Hz,1H),7.10(d, J=3.4Hz,1H),6.94(s,1H),6.83(dd,J=7.8,1.7Hz,1H),6.61(s,1H),6.43(s ,1H),4.21(s,1H),3.69(s,3H),3.12(s,1H),2.86(s,1H),2.61–2.57(m,1H).

[0057] Compound I-17: white powder, yield 91%. 1H NMR (600MHz, CDCl3) δ7.64(d,J=3.2Hz,1H),7.52(d,J=4.0Hz,1H),7.45(s,1H),7.39(d,J=2.8Hz,2H),7.26(d,J=4.6Hz,1H),7.12(s,1H),6.98( d,J=4.6Hz,1H),6.84(s,1H),6.76(d,J=3.7Hz,1H),6.64(s,1H),6.52( s,1H),4.41(s,1H),3.83(s,3H),3.51(s,1H),2.94(s,1H),2.78(s,1H).

[0058] Compound I-18: white powder, yield 83%. 1 H NMR (600MHz, CDCl3) δ7.69 (dd, J=4.2, 1.4Hz, 1H), 7.58 (d, J=2.8Hz, 1H), 7.49 (s, 1H), 7.3 4(d,J=2.7Hz,2H),7.21(d,J=1.8Hz,1H),7.17(s,1H),7.13(d,J=4.4Hz,1H),7.01(s,1H), 6.93(d,J=2.6Hz,1H),6.84(s,1H),6.72(s,1H),5.65(s,2H),4.25(s,1H),3.63(s,3H),3 .41(s,1H),2.92(s,1H),2.83(dd,J=6.4,2.3,Hz,2H),2.74(s,1H),2.22(t,J=5.1Hz,3H).

[0059] Compound I-19: white powder, yield 94%. 1 H NMR(600MHz, CDCl3) δ7.52(d,J=2.1,1H),7.47(d,J=5.1Hz,1H),7.36(s,1H), 7.20(td,J=5.6,1.8Hz,2H),7.10(d,J=3.9Hz,1H),7.06(dd,J=4.2Hz,1H),7. 01(dd,J=4.2Hz,1H),6.85(dd,J=7.8,1.7Hz,1H),6.72(s,1H),6.63(s,1H),4 .21(s,1H),3.82(s,3H),3.31(s,1H),2.99(s,1H),2.71(s,1H),1.28(9,1H).

[0060] Compound I-20: white powder, yield 94%. 1H NMR (600MHz, CDCl3) δ7.69(d,J=2.2Hz,1H),7.62(d,J=3.2Hz,1H),7.59(s,1H),7.54(s,1H)7.39(d,J= 4.3Hz,2H),7.31(s,1H),7.24(d,J=2.9Hz,1H),7.17(s,1H),7.12(dd,J=5.2,2.3Hz,1H),7.03(s,1H), 6.97(s,1H),6.92(dd,J=7.8,1.7Hz,1H),6.83(s,1H),6.71(s,1H),6.62(s,1H),4.25(s,1H),3.84(s, 3H),3.76(s,3H),3.39(s,1H),3.03(s,1H),2.86(s,1H),2.70(t,J=5.9Hz,4H),1.74(t,J=5.9Hz,4H).

[0061] Compound I-21: white powder, yield 88%. 1 H NMR (600MHz, CDCl3) δ8.08(d,J=1.4Hz,1H),7.89(d,J=1.7Hz,1H),7.58(dd,J=4.6,1.2 Hz,1H),7.49(d,J=2.3Hz,1H),7.38(s,1H),7.30(s,1H),7.17(dd,J=5.2,1.3Hz,1H),6 .97(d,J=0.9Hz,1H),6.81(t,J=1.3Hz,1H),6.55(d,J=1.9Hz,1H),3.81(s,3H),3.76(s ,3H),3.46(dd,J=4.2,1.5Hz,1H),3.15(ddd,J=8.1,4.2,1.6Hz,1H),2.86–2.81(m,1H).

[0062] Example 2, experimental methods and results of the anti-plant pathogenic fungi activity of target compound I.

[0063] The present invention uses a hyphal growth rate method to test the in vitro activity of target compounds I-1-I-21 against nine common crop pathogens, including wheat sheath blight (Rhizotonia cerealis; RC), rice sheath blight (Rhizoctonia solani; RS), wheat head blight (Fusarium graminearum; FG), corn leaf spot (Helminthosporium maydis; HM), rapeseed sclerotinia (Sclerotinia sclerotiorum; SS), tomato early blight (Alternaria solani; AS), apple ring rot (Physalospora piricola; PP), cucumber gray mold (Botrytis cinerea; BC), and pear black spot (Alternaria alternata; AA). Chlorothalonil and boscalid were used as control drugs. The compounds were dissolved in dimethyl sulfoxide to a concentration of 10 mg / L -1 The mother solution was diluted with Tween solution to a concentration of 50 mg·L -1 1 mL of the test solution was added to 9 mL of potato dextrose agar (PDA) medium. After the medium completely solidified, the test strain was inoculated. DMSO was used as a blank control. The experiment was repeated three times. After incubation at 25°C in the dark for 3-4 days, the culture dish was removed and the colony diameter was measured using the cross-hatch method. The results of the anti-plant pathogen test are shown in Table 2.

[0064] Table 2 Experimental data of anti-plant pathogenic fungi activity of target compounds I-1-I-21.

[0065]

[0066] Results showed that the novel 1-arylisoquinoline compounds exhibited moderate to significant in vitro antifungal activity against nine plant pathogenic fungi, comparable to the commercially available drugs chlorothalonil and boscalid. Therefore, the novel 1-arylisoquinoline compounds of the present invention can be used to prepare antifungal fungicides against plant pathogenic fungi.

[0067] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the essence and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A novel N-acyl tetrahydroisoquinoline compound, the structural formula of which is shown below:

2. The use of the novel N-acyltetrahydroisoquinoline compound according to claim 1 in the preparation of an anti-plant pathogenic fungicide, wherein the plant pathogenic fungus is selected from the group consisting of Rhizotonia cerealis, Rhizoctonia solani, Fusarium graminearum, Helminthosporium maydis, Sclerotinia sclerotiorum, Alternaria solani, Physalospora apiricola, Botrytis cinerea, and Alternaria alternata.

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