Novel 1-arylisoquinoline compounds and their use as fungicides against plant pathogenic fungi

Abstract

The present invention relates to novel 1-arylisoquinoline compounds and their use in preparing anti-plant pathogenic fungicides. These isoquinoline compounds have the structure of Formula (I): #imgabs0#, wherein Ar is selected from aromatic groups such as benzene, naphthalene, biphenyl, thiophene, furan, pyrazole, thiazole, and pyridine; and R1-R4 is selected from hydrogen, halogen, hydroxyl, trifluoromethyl, C1-C6 alkyl, and C1-C6 alkoxy. The compounds described herein exhibit significant inhibitory activity against various plant pathogenic fungi and can be used to prepare fungicides for controlling crop diseases.

Description

Technical Field

[0001] The present invention relates to the field of pesticide fungicides, in particular to novel 1-arylisoquinoline compounds and applications thereof in preparing anti-plant pathogenic fungicides. Background Art

[0002] Tetrahydroisoquinoline alkaloids are important members of the alkaloid family and are widely distributed in plants such as the Papaveraceae, Berberidaceae and Ranunculaceae. Its active parent nucleus is 1,2,3,4-tetrahydroisoquinoline (THIQ), which is present in a variety of bioactive molecules, drugs and agrochemicals. Natural products based on THIQ and their derivatives not only have a variety of medical activities such as anti-tumor, antibacterial, analgesic, and antiarrhythmic, but also exhibit agricultural activities such as bactericidal, insecticidal, acaricidal and antiviral. Their development and application have attracted much attention from pharmaceutical researchers. In previous studies, the applicant reported that two types of 3-arylisoquinoline compounds were invented, using quaternary ammonium isoquinoline alkaloids: Sanguinarine, Cherythrine and Berbine as the lead, and their application as anti-plant pathogenic fungicides. It was shown that the isoquinoline structure is a potential antibacterial core, laying an experimental foundation for the creation of natural anti-plant pathogenic fungicides (CN 115353488 B).

[0003] Based on previous research, the applicants used tetrahydroisoquinoline alkaloids with antibacterial activity as a lead, employed a biomimetic pesticide design strategy, simplified the lead structure, and combined it with the principle of pharmacophore splicing to design and synthesize a series of novel 1-arylisoquinoline derivatives. The results demonstrated that the novel 1-arylisoquinoline derivatives described in this invention exhibit antibacterial activity against a variety of plant pathogenic fungi.

[0004] The novel 1-arylisoquinoline 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 1-arylisoquinoline derivatives. Summary of the Invention

[0005] The present invention aims to provide novel 1-arylisoquinoline compounds and their use in preparing anti-plant pathogenic fungicides.

[0006] The novel 1-arylisoquinoline compounds of the present invention have a general structural formula as shown in Formula (I):

[0007]

[0008] In formula (I), R1-R4 are selected from hydrogen, halogen, hydroxy, trifluoromethyl, C1-C6 alkyl and C1-C6 alkoxy.

[0009] 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).

[0010]

[0011] In formula (II), R5-R 11 is selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C1-C6 alkyl and C1-C6 alkoxy.

[0012] The present invention provides a general preparation method for the novel 1-arylisoquinoline compound I, and its typical synthetic route is as follows:

[0013]

[0014] Compound I is used as a drug for the preparation of an anti-plant pathogenic fungus. 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).

[0015] Compared with the prior art, the present invention has the following advantages and effects:

[0016] This invention uses the natural antibacterial active ingredients rugenine, chrysotoxine, and scoparine as lead compounds. Using a biomimetic design strategy, with a unified biomimetic skeleton, tetrahydroisoquinoline, as the parent nucleus, key pharmacophores from amides, succinate dehydrogenase inhibitors, and biphenyl fungicides were introduced to design and synthesize a series of novel 1-arylisoquinoline compounds. Antimicrobial activity tests demonstrated that these compounds exhibit significant activity against plant pathogenic fungi. Some target compounds are comparable to the commercial fungicides chlorothalonil and boscalid, providing fundamental data for the synthesis of 1-arylisoquinoline derivatives and broader bioactivity studies. DETAILED DESCRIPTION

[0017] In the present invention, the applicant designed and synthesized novel 1-arylisoquinoline compounds having the following general structural formula:

[0018]

[0019] In formula (I), R1-R4 are selected from hydrogen, halogen, hydroxy, trifluoromethyl, C1-C6 alkyl and C1-C6 alkoxy.

[0020] 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).

[0021]

[0022] In formula (II), R5-R 11 is selected from hydrogen, halogen, nitro, difluoromethyl, trifluoromethyl, C1-C6 alkyl and C1-C6 alkoxy.

[0023] The application of novel 1-arylisoquinoline compounds as anti-plant pathogenic fungicides. It is known that isoquinoline compounds have significant inhibitory activity against the following common plant pathogenic fungi:

[0024] It has significant inhibitory activity against 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).

[0025] The general synthesis method of the 1-arylisoquinoline 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 Intermediate 5a: Dissolve 4a (2.87 g, 10 mmol, 1.0 eq.), EDCI (2.88 g, 15 mmol, 1.5 eq.), DMAP (0.25 g, 2 mmol, 0.2 eq.), and Boc-glycine (1.75 g, 10 mmol, 1.0 eq.) in 20 mL of DMF. Stir at room temperature and monitor the reaction by TLC until completion. The reaction mixture is diluted with 200 mL of ethyl acetate and washed sequentially with distilled water (20 mL x 3) and saturated brine (15 mL x 3). The organic phase is collected, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography (PE:EA) to afford 5a.

[0032] Synthesis of Intermediate 6a: Dissolve 5a (4.44 g, 10 mmol, 1.0 eq.) in 20 mL of dichloromethane, add TFA (5 mL), and stir. Monitor the reaction by TLC until completion. Adjust the pH to 7-8 with sodium hydroxide solution, wash with saturated brine (15 mL x 3), and collect the organic phase, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and separate by column chromatography (DCM:MeOH) to obtain 6a. The synthesis of other intermediates 6 was similar to that of 6a.

[0033] 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.), add 1-2 drops of DMF, and stir for 3 h. Monitor the reaction by TLC until complete. Concentrate under reduced pressure to obtain the crude acyl chloride for later use. Add 6a (0.34 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). Slowly add the solution dropwise using a constant pressure funnel at a constant rate and allow to react overnight. Monitor the reaction by TLC until 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.

[0034] Compound I-1: white powder, yield 94%, mp 165–167 °C. 1 H NMR(600MHz, CDCl3)δ7.93(d,J=2.6Hz,1H),7.55(d,J=16.4Hz,1H),7.28–7.13(m,1H),7.02(dd,J=6.7,3.1Hz,1H),6 .97(dd,J=8.6,2.4Hz,1H),6.93(ddd,J=9.8,4.5,2.5Hz,1H),6.80(5.87)(s,1H),6.68(d,J=4.8Hz,1H),6.50(d,J=1 8.9Hz,1H),4.39–4.23(m,2H),3.93(d,J=2.9Hz,3H),3.90(d,J=2.0Hz,3H),3.77(3.84)(d,J=9.3Hz,3H),3.70(ddd, J=13.9,6.0,2.9Hz,1H),3.42(dddd,J=20.6,16.2,11.6,4.4Hz,1H),3.03–2.90(m,1H),2.80(dt,J=16.4,3.6Hz,1H). 13 C NMR(100MHz,CDCl3)δ166.73(166.62),162.81(d, 1 J CF =246.6Hz),161.30,148.68,148.06,144.35(144.29),133.62,130.38(130.30),129.82(129.91),126.15 ,125.84,124.18,116.19,115.67(115.46),115.30(115.09),114.73(114.52),111.41,111.30,109.55(d, 1 J CF =234.9Hz),56.05,55.97,55.09,41.65,39.44,38.85,28.16,26.89.

[0035] The synthesis methods of the remaining target compounds I are the same as I-1.

[0036] According to the preparation method of Example 1, a series of derivatives I-1 to I-24 were obtained, and their structures are shown in Table 1.

[0037] Table 1 Structural formula of series target compound I

[0038]

[0039]

[0040] The physicochemical data of some representative compounds are as follows:

[0041] Compound I-2: white powder, yield 87%, mp 123–125°C. 1 H NMR (600MHz, CDCl3) δ7.61 (dt, J=4.1, 2.0Hz, 1H), 7.49 (dd, J=5.0, 1.2Hz, 1H), 7.34–7.30 (m, 1H), 7.28–7. 25(m,2H),7.21–7.16(7.13–7.12)(m,2H),7.08(dd,J=5.0,3.7Hz,1H),6.78(6.60)(s,1H),6.69(d,J=2.8H z,1H),6.49(5.89)(s,1H),4.34–4.25(4.51–4.50)(m,2H),3.90(s,3H),3.77(3.84)(s,3H),3.72(ddd,J=13. 9,5.8,2.6Hz,1H),3.41(ddd,J=13.8,11.5,4.4Hz,1H),3.03–2.91(m,1H),2.80(ddd,J=16.2,4.2,2.6Hz,1H). 13 C NMR (150MHz, CDCl3) δ166.66,161.82,148.52,147.99,140.35,138.44,133.75,130.30,130.12,129.03(128.89),128.6 7,128.52,127.75,126.11,125.80,111.20,110.99,56.05,56.00,55.00,41.90(42.15),38.67(37.64),28.34(27.12).

[0042] Compound I-3: white powder, yield 93%, mp 114–116 °C. 1H NMR(600MHz, CDCl3)δ7.96(7.53)(s,1H),7.37(s,1H),7.32–7.24(m,2H),7.21–7.05(m,2H),6.79 (6.57)(s,1H),6.69(d,J=3.9Hz,1H),6.48(5.84)(s,1H),4.27(4.53–4.42)(dd,J=4.0,2.2Hz,2H ),3.97(d,J=3.4Hz,4H),3.90(s,3H),3.77(s,3H),3.68(ddd,J=13.8,6.0,2.7Hz,1H),3.40(ddd, J=13.8,11.5,4.4Hz,1H),2.99(ddt,J=19.1,13.1,7.0Hz,1H),2.80(ddd,J=16.2,4.3,2.6Hz,1H). 13 C NMR (150MHz, CDCl3) δ166.42,160.31,148.49,147.95,140.23,139.10(q, 2 J CF =37.7Hz),134.79,133.69,130.71,130.07,128.97(128.95),128.59,125.99,125.75,120.82(d, 1 J CF =269.3Hz),116.64,111.14,110.92,55.99,55.94,54.86,41.87,39.76,38.57,28.22.

[0043] Compound I-4: white powder, yield 85%, mp 129–131 °C. 1 H NMR (400MHz, CDCl3) δ7.51–7.43(m,1H),7.33–7.22(m,2H),7.17(s,1H),7.16–7.06(m,1 H),6.76(6.55)(s,1H),6.67(s,1H),6.46(5.78)(s,1H),4.26(4.50–4.43)(d,J=3.9Hz,2 H),3.88(s,3H),3.75(3.82)(s,3H),3.72–3.60(m,1H),3.39(ddd,J=13.8,11.6,4.4Hz,1 H), 2.98 (ddd, J=16.8, 11.4, 5.7Hz, 1H), 2.79 (ddd, J=16.2, 4.4, 2.6Hz, 1H), 2.74 (s, 3H). 13C NMR (100MHz, CDCl3) δ168.25,165.66,158.67,148.66,148.14,141.12(d, 2 J CF =36.9Hz),140.21,134.69,133.92,130.21,129.14,129.03,128.76,125.95,125.75,120.28(d, 1 J CF =272.1Hz),111.25,111.04,56.11,56.06,55.06,42.54,38.66,28.34,19.34.

[0044] Compound I-5: white powder, yield 92%, mp 124–126 °C. 1 H NMR (400MHz, CDCl3) δ7.58,7.46,7.34–7.29(m,1H),7.26–7.23(m,2H),7.18–7.14(m, 2H),7.08–6.97(m,1H),6.73(6.61)(s,1H),6.59(d,J=3.6Hz,1H),6.52(6.03)(s,1H), 4.42–4.31(4.49–4.52)(m,2H),3.92(s,3H),3.74(ddd,J=13.9,5.8,2.6Hz,1H),3.52 (ddd,J=13.8,11.5,4.4Hz,1H),3.16–2.92(m,1H),2.83(ddd,J=16.2,4.2,2.6Hz,1H).

[0045] Compound I-6: white powder, yield 88%, mp 142–144 °C. 1H NMR (400MHz, CDCl3) δ7.82,7.68(m,1H),7.56,7.43–7.38(m,1H),7.27–7.19(m,2H),7.16–7.04(m,2H),6 .99–6.94(m,1H),6.81(6.59)(s,1H),6.57(d,J=4.2Hz,1H),6.49(6.05)(s,1H),4.38–4.30(4.47–4.44) (m,2H),3.87(s,3H),3.68(ddd,J=13.9,10.8,4.6Hz,1H),3.46(ddd,J=13.8,11.5,4.4Hz,1H),3.23–2.9 8(m,1H),2.81(ddd,J=13.8,11.3,4.4Hz,1H),2.34(s,3H),2.21(q,J=5.5Hz,2H),1.51(t,J=5.5Hz,3H).

[0046] Compound I-7: white powder, yield 94%, mp 131–133 °C. 1 H NMR(400MHz, CDCl3)δ7.83(s,1H),7.61(d,J=5.0,1H),7.42–7.31(m,1H),7.26–7.23(m,2H),7.18– 7.13(7.13–7.12)(m,2H),7.05(dd,J=5.0,3.7Hz,1H),6.82(6.56)(s,1H),6.62(d,J=1.6Hz,1H),6 .36(5.79)(s,1H),4.42–4.31(m,2H),3.86(s,3H),3.73(3.79)(s,3H),3.63(ddd,J=12.1,4.6,1.8 Hz,1H),3.36(ddd,J=13.8,11.5,4.4Hz,1H),3.01–2.87(m,1H),2.69(ddd,J=15.1,4.6,2.5Hz,1H).

[0047] Compound I-8: white powder, yield 92%, mp 111–113 °C. 1H NMR(600MHz,DMSO-d6)δ8.69(t,J=5.9Hz,1H),7.82–7.79(m,1H),7.77–7.72(m,1H),7.62(d,J=2.2Hz,1H),7 .33(dd,J=8.4,2.2Hz,1H),7.17–7.13(m,1H),6.97(d,J=8.4Hz,1H),6.85(s,1H),6.68(s,1H),6.63(s,1H),4 .32(dd,J=16.9,6.2Hz,1H),4.12(dd,J=16.8,5.6Hz,1H),3.90(dd,J=11.3,7.0Hz,1H),3.76(s,3H),3.60(s ,2H),3.41(ddd,J=14.4,10.7,4.5Hz,1H),2.98(ddd,J=16.4,10.6,5.7Hz,1H),2.86(dt,J=16.6,4.0Hz,1H). 13 C NMR (100MHz, DMSO-d6) δ168.30,161.81,148.59,147.94,140.06,139.99,134.46,133.11,132.31,131.3 5,129.48,128.83,128.41,127.64,127.22,126.56,112.48,111.25,56.01,55.95,53.27,41.40,28.35.

[0048] Compound I-9: white powder, yield 90%, mp 133–135 °C. 1 H NMR(400MHz, CDCl3)δ7.95(t,J=2.7Hz,1H),7.45–7.30(m,1H),7.00(td,J=8.6,6.5Hz,1H),6.9 0(s,1H),6.85–6.74(m,2H),6.68(d,J=5.3Hz,1H),6.47(d,J=2.9Hz,1H),4.29(4.64–4.46)(t,J =3.7Hz,2H),3.96(d,J=7.4Hz,3H),3.90(d,J=2.6Hz,3H),3.78(d,J=18.1Hz,3H),3.79–3.72(m, 1H), 3.52 (ddd, J=14.0, 11.5, 4.4Hz, 1H), 3.03 (qd, J=12.0, 11.3, 6.6Hz, 1H), 2.92–2.68 (m, 1H).

[0049] Compound I-10: white powder, yield 92%, mp 122–124 °C. 1 H NMR(400MHz, CDCl3)δ7.91(s,1H),7.48–7.41(m,1H),6.96(t, 1 J CF =54.1Hz,1H),6.86(dd,J=8.2,6.5Hz,2H),6.71(s,1H),6.67(s,1H),6.4 4(s,1H),4.27(d,J=4.0Hz,2H),3.92(s,3H),3.88(s,3H),3.77(3.85)(s ,3H),3.70(ddd,J=13.8,5.8,3.0Hz,1H),3.36(ddd,J=13.8,11.2,4.4Hz,1H),2.96(ddd,J=16.6,11.2,5.7Hz,1H),2.78(dt,J=16.1,3.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ166.92,161.22,153.28–149.74(m),148.86,148.13,144.64–139.94(m),138.09,134.05,126.18,124.68,116 .14,113.28,113.05(112.99),112.84(112.89),111.30,110.95,110.87,108.62,56.04,55.97,54.38,41.77,39.53,38.76,28.08.

[0050] Compound I-11: white powder, yield 93%, mp 120–122 °C. 1H NMR (400MHz, CDCl3) δ7.92(s,1H),7.46(dd,J=19.5,2.1Hz,1H),7.38(d,J=4.2Hz,1H),7.14(ddd,J=1 6.4,8.4,2.2Hz,1H),6.89(6.08)(s,1H),6.83(d,J=8.5Hz,1H),6.68(d,J=4.3Hz,1H),6.48(s,1H),4 .46–4.17(m,2H),3.94(d,J=9.8Hz,4H),3.89(s,3H),3.75(3.79)(s,3H),3.74–3.71(m,1H),3.46(dd d,J=14.1,11.6,4.5Hz,1H),3.05(ddt,J=17.4,11.5,6.7Hz,1H),2.86(ddd,J=16.4,4.5,2.2Hz,1H). 13 C NMR (100MHz, CDCl3) δ167.01,160.39,148.74,148.25,138.14,134.89,134.24,134.12,131.76,129.84,126.90,126.05,125.83,120.75(d, 1 J CF =269.6Hz),116.54,111.54,110.70,55.97,55.95,53.48,41.74,39.61,39.31,28.36,26.89.

[0051] Compound I-12: white powder, yield 90%, mp 121–123 °C. 1 H NMR (400MHz, CDCl3) δ7.94 (s, 1H), 7.55–7.46 (m, 1H), 7.28 (d, J = 3.8Hz, 1H), 7.12 (d, J = 1.9Hz, 2H), 7.01 (t, 1 J CF =54.1Hz,1H),6.76(s,1H),6.70(s,1H),6.47(s,1H),4.30(d,J=4.1Hz,2H),3.95(s,3H),3.92(s,3H),3.80(s,3H),3.73(ddd,J=1 3.3, 6.0, 2.9Hz, 1H), 3.41 (ddd, J=13.8, 11.3, 4.4Hz, 1H), 3.00 (ddd, J=16.7, 11.2, 5.7Hz, 1H), 2.82 (ddd, J=16.3, 4.4, 2.8Hz, 1H). 13CNMR (100MHz, CDCl3) δ166.86,161.24,148.76,148.09,145.13,144.18,135.13,133.90,128.09,127.15,1 26.11,124.78,116.15,113.20,111.29,110.86,108.53,56.07,55.96,54.66,41.75,39.55,38.81,29.84.

[0052] Compound I-13: white powder, yield 86%, mp 108–110°C. 1 H NMR(400MHz, CDCl3)δ7.60(dd,J=3.7,1.2Hz,1H),7.48(dd,J=5.0,1.2Hz,1H),7.34–7.24(m,2H) ,7.11–7.01(m,2H),7.07(dd,J=5.0,3.7Hz,1H),6.72(s,1H),6.68(s,1H),6.46(s,1H),4.30(t, J=4.1Hz,2H),3.89(s,3H),3.78(3.86)(s,3H),3.73(ddd,J=13.8,5.9,2.9Hz,1H),3.39(ddd,J= 13.8,11.3,4.4Hz,1H),2.97(ddt,J=18.4,12.8,6.4Hz,1H),2.81(ddd,J=16.2,4.3,2.8Hz,1H). 13 C NMR (100MHz, CDCl3) δ166.86,161.79,148.77,148.11,145.13,138.32,135.17,130.27,128.51,128.1 3,127.69,127.15,126.14,126.00,124.73,111.29,110.85,56.08,55.97,54.77,41.85,38.84,28.17.

[0053] Compound I-14: white powder, yield 88%, mp 113–115 °C. 1H NMR(400MHz, CDCl3)δ7.97(d,J=1.2Hz,1H),7.42–7.38(m,1H),7.28(q,J=1.5Hz,1H) ,7.14–6.96(m,2H),6.75(s,1H),6.70(s,1H),6.47(s,1H),4.30(d,J=4.0Hz,2H),3.9 7(s,3H),3.91(s,3H),3.80(3.87)(s,3H),3.72(ddd,J=13.9,6.0,2.8Hz,1H),3.40( ddd,J=13.8,11.3,4.4Hz,1H),3.06–2.91(m,1H),2.82(ddd,J=16.2,4.3,2.8Hz,1H). 13 C NMR (100MHz, CDCl3) δ166.75,160.35,148.78,148.11,145.07,139.28(d, 2 J CF =37.7Hz),135.58,135.14,134.76,128.11,127.14,126.08,124.73,120.81(d, 1 J CF =269.5Hz),116.61,111.29,110.85,56.07,55.96,54.69,41.86,39.77,38.80,28.09.

[0054] Compound I-15: white powder, yield 91%, mp 125–127 °C. 1 H NMR(600MHz, CDCl3)δ7.94(d,J=12.6Hz,1H),7.66–7.55(m,1H),7.36–7.25(m,3H),7.20(t, J=9.1Hz,1H),6.95(6.72)(s,1H),6.70(6.48)(s,1H),6.49(6.17)(s,1H),4.32(d,J=3.9Hz, 2H),3.98(d,J=4.4Hz,3H),3.94–3.90(m,3H),3.80(d,J=5.3Hz,1H),3.78–3.75(m,3H),3.5 5(ddd,J=14.5,11.0,4.4Hz,1H), 3.04(tt,J=11.1,5.3Hz,2H), 2.92(dt,J=16.2,3.8Hz,1H).

[0055] Compound I-16: white powder, yield 84%, mp 139–141°C.1 H NMR (400MHz, CDCl3) δ7.67–7.54(m,1H),7.47–7.38(m,1H),7.36–7.26(m,1H),7.20(t ,J=9.1Hz,1H),6.91(s,1H),6.70(s,1H),6.48(d,J=2.8Hz,1H),4.32(d,J=4.0Hz,1H), 3.91(d,J=6.3Hz,3H),3.76(s,3H),3.74(q,J=4.8,3.5Hz,1H),3.56(ddd,J=13.9,10. 8,4.6Hz,1H),3.03(td,J=10.8,4.9Hz,1H),2.92(dt,J=16.1,3.9Hz,1H),2.75(s,3H).

[0056] Compound I-17: white powder, yield 91%, mp 116–118 °C. 1 H NMR (400MHz, CDCl3) δ7.47–7.40(m,1H),7.37–7.25(m,1H),7.21(dd,J=8.3,1.9Hz ,1H),6.92(t,J=8.1Hz,1H),6.85(s,1H),6.68(s,1H),6.47(d,J=3.8Hz,1H),4.30( d,J=4.0Hz,1H),3.90(d,J=4.1Hz,3H),3.77(s,3H),3.72(q,J=2.5Hz,1H),3.54(dd d,J=13.9,11.3,4.4Hz,1H),3.11–2.95(m,1H),2.88(ddd,J=16.2,4.4,2.7Hz,1H).

[0057] Compound I-18: white powder, yield 88%, mp 113–115 °C. 1H NMR(600MHz, CDCl3)δ7.79(d,J=3.4,1H),7.54(d,J=2.6,1H),7.41–7.36(m,1H),7.32–7.2 7(m,2H),7.23–7.17(7.12–7.10)(m,2H),7.08(dd,J=5.0,3.7Hz,1H),6.96(s,1H)6.74(s,1 H),6.66(d,J=2.9Hz,1H),6.51(6.03)(s,1H),4.23–4.14(m,2H),3.90(s,3H),3.68(ddd,J =11.2,4.9,2.3Hz,1H),3.48(ddd,J=12.8,8.4,4.6Hz,1H),3.03–2.91(m,1H),2.80(m,1H).

[0058] Compound I-19: white powder, yield 83%, mp 133–135 °C. 1 H NMR(600MHz, CDCl3)δ7.68(dt,J=3.4,1.2Hz,1H),7.51(d,J=2.8,1H),7.41–7.34(m,1H),7.31–7.26(m,2H), 7.17–7.13(m,2H),6.99(dd,J=4.2,2.1Hz,1H),6.82(6.53)(s,1H),6.61(d,J=1.8Hz,1H),6.44(5.92)(s,1H) ,4.34–4.25(m,2H),3.90(s,3H),,3.72(ddd,J=13.9,5.8,2.6Hz,1H),3.41(ddd,J=13.8,11.5,4.4Hz,1H),3. 03–2.91(m,1H),2.80(ddd,J=16.2,4.2,2.6Hz,1H),2.58(qdd,J=9.4,4.2,1.0Hz,1H),1.82(t,J=6.8Hz,1H).

[0059] Compound I-20: white powder, yield 87%, mp 149–151 °C. 1H NMR (400MHz, CDCl3) δ8.41(s,1H),8.37(s,1H),8.37(t,J=5.3Hz,1H),7.73(d,J=3.2Hz,1H),7 .61(dd,J=4.3,1.4Hz,1H),7.39(s,1H),7.21(s,1H),7.03(dd,J=6.4,5.3Hz,1H),6.92(s,1H), 6.74(t,J=1.0Hz,1H),5.97(s,2H),4.07–3.81(m,2H),3.90(dd,J=7.3,3.9Hz,1H),3.83(s,3H ),3.72(s,3H),3.52–3.41(m,1H),2.97(dd,J=5.8,2.4,1H),2.73(ddd,J=8.2,2.9,0.6Hz,1H).

[0060] Compound I-21: white powder, yield 94%, mp 128–130 °C. 1 H NMR (600MHz, CDCl3) δ7.79(dt,J=5.6,1.8Hz,1H),7.64(s,1H),7.53(dd,J=6.2,2.1Hz,1H),7.42(s,1H),7.33–7. 30(m,1H),7.29–7.25(m,2H),7.22–7.13(m,2H),7.01(d,J=3.7Hz,1H),6.88(s,1H),6.64(d,J=2.2Hz,1H),6.32(s ,1H),4.42–4.30(m,2H),3.86(s,3H),3.77(s,3H),3.65(dd,J=8.8,2.6Hz,1H),3.41(dd,J=6.5,1.4Hz,1H),3.21 (t,J=5.5Hz,2H),2.94–2.83(m,1H),2.80(ddd,J=13.2,4.6,1.6Hz,1H),2.01–1.93(m,2H),1.21(t,J=5.6Hz,3H),

[0061] Compound I-22: white powder, yield 91%, mp 134–136 °C. 1H NMR (400MHz, CDCl3) δ7.84(dt,J=5.6,1.8Hz,1H),7.72(s,1H),7.69(dd,J=6.2,2.1Hz,1H),7.53(s,1H),7 .48(s,1H),7.39(s,1H),7.33–7.28(m,1H),7.24–7.20(m,2H),7.09–7.00(m,2H),6.97(d,J=3.7Hz,1H),6 .88(s,1H),6.80(t,J=54.9Hz,1H),6.71(d,J=2.6Hz,1H),6.28(s,1H),4.21–4.13(m,2H),3.81(s,3H),3. 72(s,3H),3.59(dd,J=8.8,2.6Hz,1H),3.38(dd,J=6.5,1.4Hz,1H),2.94–2.83(m,1H),2.76–2.68(m,1H).

[0062] Compound I-23: white powder, yield 84%, mp 127–129°C. 1 H NMR (400MHz, CDCl3) δ7.83(d,J=2.2,1H),7.61(d,J=1.8,1H),7.48–7.41(m,1H ),7.34–7.28(m,2H),7.21(s,1H),7.14–7.10(m,2H),6.89(s,1H)6.73(s,1H), 6.64(d,J=2.1Hz,1H),6.49(s,1H),4.32–4.24(m,2H),3.73–3.65(m,1H),3.46 (ddd,J=10.2,6.4,1.2Hz,1H),3.05–2.95(m,1H),2.80(dd,J=8.4,2.2Hz,1H).

[0063] Compound I-24: white powder, yield 81%, mp 141–143 °C. 1H NMR (400MHz, CDCl3) δ7.73 (d, J = 3.1, 1H), 7.68 (s, 1H), 7.63 (s, 1H), 7.54 (d, J = 2.4, 1H), 7. 44–7.39(m,1H),7.32–7.27(m,2H),7.19(s,1H),7.08–6.99(m,2H),6.85(s,1H)6.79(s,1H) ,6.66(d,J=1.6Hz,1H),6.52(s,1H),4.26–4.20(m,2H),3.53–3.45(m,1H),3.38(ddd,J=12 .4,65.8,1.3Hz,1H),3.11–3.04(dd,J=7.4,2.8Hz,1H),2.80(ddd,J=10.4,6.2,1.1Hz,1H).

[0064] Example 2, experimental methods and results of the anti-plant pathogenic fungi activity of target compound I.

[0065] The present invention uses a hyphal growth rate method to test the in vitro activity of the target compound I-1-I-24 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 compound was 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.

[0066] Table 2 Experimental data of the anti-plant pathogenic fungi activity of target compounds I-1-I-24.

[0067]

[0068] 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.

Claims

1. New 1-arylisoquinoline compounds, the structural formula of which is shown below 2. The use of the novel 1-arylisoquinoline compound according to claim 1 in the preparation of an anti-plant pathogenic fungus drug, wherein the plant pathogenic fungus is selected from the group consisting of wheat sheath blight fungus (Rhizotonia cerealis), rice sheath blight fungus (Rhizoctonia solani), wheat head blight fungus (Fusarium graminearum), corn leaf blight fungus (Helminthosporium maydis), rapeseed sclerotinia fungus (Sclerotinia sclerotiorum), tomato early blight fungus (Alternaria solani), apple ring rot fungus (Physalospora piricola), cucumber gray mold fungus (Botrytis Cinerea) and pear black spot fungus (Alternaria alternata).

Images