Application of indole-4, 5-azepine compounds in prevention and treatment of plant disease fungi and prevention and treatment method of indole-4, 5-azepine compounds

Abstract

The invention discloses application of indole-4, 5-azepine compounds in prevention and treatment of plant disease fungi and a prevention and treatment method of the indole-4, 5-azepine compounds, and belongs to the technical field of plant disease prevention and treatment. The indole-4, 5-azepine compound has excellent inhibitory activity on four common pathogenic bacteria, such as valsa mali, fusarium graminearum, botrytis cinerea and peanut rhododendron verjuan, so that the indole-4, 5-azepine compound has important application value in the field of agricultural germ control.

Description

Technical Field

[0001] This invention belongs to the field of plant disease control technology, specifically relating to the use of indole-4,5-azazolide compounds in the control of plant disease fungi and their control methods. Background Technology

[0002] Fungal diseases constitute the largest category of plant diseases, causing severe damage and widespread distribution, resulting in significant losses to agricultural production. Common agricultural pathogens pose numerous challenges to agricultural production. For example, apple rot fungus severely damages apple tree branches, trunks, fruits, and seedlings, impacting the apple industry; Fusarium wilt fungus damages wheat, corn, and other gramineous crops, secreting various polymyxins, seriously threatening food and food safety; gray mold fungus of tomato damages tomato fruits, leaves, and petioles, and is widespread in tomato-growing areas; white mold fungus of peanut mainly affects the stems, pedicels, pods, and roots of peanut plants, severely impacting peanut yield and quality, becoming a major factor restricting peanut production and quality. These pathogens typically overwinter in the soil, diseased plant debris, and seeds, spreading through various routes such as rainwater, air currents, and agricultural operations. Once an outbreak occurs, it can cause severe damage to crops, reduce the quality and yield of agricultural products, increase agricultural production costs, and threaten the sustainable development of the agricultural economy. Agricultural control methods, such as enhanced management, crop rotation, and removal of diseased plant debris, are difficult to implement, and crop rotation is often limited by land resources. Biological control using microorganisms and their metabolites, while more environmentally friendly, is inconsistent in effectiveness and easily affected by environmental factors. Chemical control, the most commonly used method, can quickly and effectively control diseases, but long-term use can lead to drug resistance in pathogens, reducing control efficacy and even rendering some traditional agents ineffective. These shortcomings pose challenges to the control of agricultural pathogens, necessitating the continuous exploration of more effective control strategies. Therefore, there is an urgent need to find new active molecules in the field of chemical control to address the problem of drug resistance. Summary of the Invention

[0003] This invention provides the application of indole-4,5-azazepine compounds in the preparation of drugs for controlling plant pathogenic fungi.

[0004] In the above applications, the plant pathogenic fungi are selected from one or more of the following: apple rot fungus, grain rot fungus, tomato gray mold fungus, and peanut white mold fungus.

[0005] In the above applications, the structural formula of the indole-4,5-azidophene compound is as follows: ; Among them, R 1 Selected from one of p-toluenesulfonyl, p-chlorobenzenesulfonyl, p-methoxybenzenesulfonyl, 2-thiophenesulfonyl, and 4-morpholinesulfonyl; R2 Selected from one of hydrogen, halogen, and methyl; R 3 The group is selected from any feasible position on the benzene ring, specifically from one of hydrogen, halogen, methyl, methoxy, methoxycarbonyl, and drug molecule derivatives; R 4 Selected from hydrogen or methyl; R 5 It is selected from one of hydrogen, methyl, and phenyl; X is selected from one of S and O.

[0006] In specific implementation schemes, the indole-4,5-azidophene compound may be selected from the following structural formulas: This invention provides a pharmaceutical formulation for controlling plant pathogenic fungi, the pharmaceutical formulation containing the above-mentioned indole-4,5-azazepine compounds; it may also contain pesticide-acceptable excipients, carriers, excipients or diluents.

[0007] The dosage form of the above-mentioned pharmaceutical preparations may be selected from liquid, suspension, emulsifiable concentrate, wettable powder, tablet or granule.

[0008] The concentration of indole-4,5-nazazepine compounds in the above-mentioned pharmaceutical preparations is 10~200 mg / L; preferably 12.5 mg / L, 25 mg / L, 50 mg / L, or 100 mg / L.

[0009] This invention provides a method for preventing and controlling plant pathogenic fungi, wherein the method comprises spraying or drenching the roots of diseased plants with the above-mentioned pharmaceutical preparation containing indole-4,5-azopyridine compounds to achieve the effect of preventing and controlling plant pathogenic fungi.

[0010] In the above-mentioned methods for controlling plant pathogenic fungi, the concentration of indole-4,5-aziridine compounds in the drug preparation is 10~200 mg / L; preferably 12.5 mg / L, 25 mg / L, 50 mg / L, or 100 mg / L.

[0011] In the above-mentioned method for controlling plant disease fungi, the plant disease fungi are selected from one or more of the following: apple rot fungus, grain rot fungus, tomato gray mold fungus, and peanut white mold fungus.

[0012] The beneficial effects of this invention are as follows: The indole-4,5-azazepine compounds provided by this invention have excellent inhibitory activity against four common pathogenic fungi: apple rot fungus, cereal Fusarium wilt fungus, tomato gray mold fungus, and peanut white mold fungus. These compounds can be used to prepare pesticide formulations to achieve better control of the above-mentioned plant pathogenic fungi, thus having important application value and prospects in the field of agricultural pathogen control. Attached Figure Description

[0013] Figure 1 This image shows an inhibitory diagram of bacteria that cause apple rot.

[0014] Figure 2 This is an image showing the inhibition of Fusarium graminearum, the pathogen of the cereal disease.

[0015] Figure 3 This is a diagram showing the inhibition of gray mold, the pathogen that causes tomato fungus.

[0016] Figure 4 An image showing the inhibition of white mold pathogens in peanuts. Detailed Implementation

[0017] The steps for preparing indole-4,5-azitrazine compounds are as follows: 0.2 mmol of an indole-4,5-azidophene compound and 0.24 mmol of indole or an indole derivative were placed in a sealed tube, and 2 mL of chloroform and 0.6 mmol of trifluoroacetic acid were added. The system temperature was maintained at 60 °C, and the mixture was continuously stirred. The reaction was monitored by spotting the sample onto a thin-layer chromatography plate until the reactants were completely reacted. After the reaction was complete, the product was purified by column chromatography. The purified product was further evaporated by rotary evaporation to obtain an indole-4,5-azidophene compound.

[0018] The structural formulas of the above indole-4,5-azitrazine compounds are as follows: Among them, R 1 Selected from one of p-toluenesulfonyl, p-chlorobenzenesulfonyl, p-methoxybenzenesulfonyl, 2-thiophenesulfonyl, and 4-morpholinesulfonyl; R 2 Selected from one of hydrogen, halogen, and methyl; R 3 The group is selected from any feasible position on the benzene ring, specifically from one of hydrogen, halogen, methyl, methoxy, methoxycarbonyl, and drug molecule derivatives; R 4 Selected from hydrogen or methyl; R 5 It is selected from one of hydrogen, methyl, and phenyl; X is selected from one of S and O.

[0019] The structural formulas of the above-mentioned indole-azaphene-spiro-benzothiophene alcohols are as follows: Among them, R 1 Selected from one of p-toluenesulfonyl, p-chlorobenzenesulfonyl, p-methoxybenzenesulfonyl, 2-thiophenesulfonyl, and 4-morpholinesulfonyl; R 2 At position 5 of the benzene ring, the specific atom is selected from hydrogen, halogen, or methyl; X is selected from S or O.

[0020] The above-mentioned indole derivatives are selected from one of the following structural formulas: Based on the above method, this invention prepared 32 indole-4,5-azazepine compounds, and the specific preparation process is illustrated in the following examples.

[0021] The chemical reaction formula is shown below: 0.2 mmol of 4-(pyrrolidone-1-yl)-1-p-toluenesulfonyl-1H-indole-3-spiro-benzothiophene-3-ol and 0.24 mmol of indole were placed in a sealed tube, and 2 mL of chloroform and 0.6 mmol of trifluoroacetic acid were added. The system temperature was maintained at 60 °C, and the mixture was continuously stirred. The reaction was monitored by spotting the sample onto a thin-layer chromatography plate until the reactants were completely reacted. After the reaction was complete, the product was purified by column chromatography (eluent:PE:EA:DCM=7:1:1). The purified product was further evaporated by rotary evaporation to obtain the target product.

[0022] Other materials used in this invention, unless otherwise stated, are commercially available. Other terms used in this invention, unless otherwise specified, generally have the meanings commonly understood by those skilled in the art. The invention is further described in detail below with reference to specific embodiments and data. The following embodiments are merely illustrative and not intended to limit the scope of the invention in any way.

[0023] The NMR data of the 32 indole-4,5-azidophene compounds are shown below: Example 1 10-(benzo[b]thiophen-2-ylmethyl)-5-(1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3 e]indole : White solid; 114.4 mg, 95% yield; mp 207‒209 °C; Rf = 0.33 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 11H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H), 7.79–7.73 (m, 3H), 7.64 (d, J = 7.7 Hz, 1H), 7.44 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.36–7.27 (m, 4H), 7.24 (d, J = 8.0 Hz, 2H), 7.16 (t, J = 7.6 Hz, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.98 (s, 1H), 6.90 (d, J = 2.4 Hz, 1H), 6.88 (d, J = 8.7 Hz, 1H), 4.51 (dd, J = 7.9, 3.3 Hz, 1H), 4.41 (s, 2H), 4.22 (s, 1H), 2.75 (dt, J = 13.0, 5.1 Hz, 1H), 2.55 (dt, J = 12.3, 5.2 Hz, 1H), 2.38 (s, 3H), 2.14–2.04 (m, 2H), 1.61 (p, J = 6.0 Hz, 2H); 13 13C NMR (126 MHz, CDCl3): δ 144.9, 143.6, 140.2, 139.8, 136.6, 135.6, 135.4, 131.0, 130.0, 128.0, 127.2, 127.1, 124.5, 124.4, 124.2, 123.3, 122.9, 122.4, 122.0, 121.9, 121.5, 120.1, 119.9, 119.3, 118.8, 111.2, 106.2, 47.7, 41.1, 32.2, 29.2, 28.6, 21.8; HRMS (ESI) m / z: [M + H] + calculated for C 36 1H 32 N3O2S2, 602.1930; found, 602.1934。

[0024] Example 2 10-(benzo[b]thiophen-2-ylmethyl)-5-(1H-indol-3-yl)-8-((4-methoxyphenyl)sulfonyl)-1,2,3,4,5,8 hexahydroazepino[2,3-e]indole: Whitesolid; 111.2 mg, 90% yield; mp 184‒186 °C; Rf = 0.28 (petroleum ether / acetone= 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1, 7 / 1 / 2 then DCM; 1 H NMR(500 MHz, CDCl3): δ 7.92 (s, 1H), 7.84–7.79 (m, 2H), 7.76 (d, J = 7.8 Hz,1H), 7.66–7.62 (m, 1H), 7.43 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.36–7.31 (m,3H), 7.29 (td, J = 7.5, 1.5 Hz, 1H), 7.16 (ddd, J = 8.1, 6.9, 1.1 Hz, 1H),7.03 7.00 (m, 1H), 6.97 (s, 1H), 6.91–6.86 (m, 4H), 4.52 (dd, J = 7.9, 3.3Hz, 1H), 4.41 (s, 2H), 4.22 (s, 1H), 3.81 (s, 3H), 2.76 (dt, J = 12.7, 4.8Hz, 1H), 2.61–2.51 (m, 1H), 2.15–2.04 (m, 2H), 1.63–1.58 (m, 2H); 1313C NMR (126 MHz, CDCl3): δ 163.8, 143.64, 143.56, 140.2, 139.8, 136.6, 135.6, 130.9, 129.9, 129.4, 128.0, 127.1, 124.5, 124.4, 124.2, 123.3, 122.9, 122.4, 122.0, 121.9, 121.5, 120.1, 119.9, 119.2, 118.8, 114.5, 111.2, 106.2, 55.8, 47.7, 41.1, 32.2, 29.2, 28.6; HRMS (ESI) m / z: [M + H] + calcd for C 36 H 32 N3O3S2, 618.1880; found, 618.1182。

[0025] Example 3 10-(benzo[b]thiophen-2-ylmethyl)-8-((4-chlorophenyl)sulfonyl)-5-(1H-indol-3-yl)-1,2,3,4,5,8 hexahydroazepino[2,3-e]indole: White solid; 115.7 mg, 93% yield; mp 189‒191°C; Rf = 0.25 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc / DCM = 10 / 1 / 1, 7 / 1 / 2 then DCM; 11H NMR (500 MHz, CDCl3): δ 10.81 (s, 1H), 7.92 (d, J = 8.6 Hz, 2H), 7.84 (d, J = 7.9 Hz, 1H), 7.77–7.71 (m, 1H), 7.71–7.63 (m, 3H), 7.37–7.25 (m, 3H), 7.21–7.15 (m, 3H), 7.06–7.00 (m, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.76–6.69 (m, 1H), 4.63 (d, J = 17.1 Hz, 1H), 4.59–4.49 (m, 2H), 4.40 (dt, J = 7.9, 3.6 Hz, 1H), 2.82 (dq, J = 14.2, 4.8 Hz, 1H), 2.49–2.43 (m, 1H), 2.00–1.90 (m, 2H), 1.50 (p, J = 5.8 Hz, 2H); 13 13C NMR (126 MHz, CDCl3): δ 144.5, 143.1, 139.8, 139.5, 138.9, 136.4, 135.6, 134.7, 131.2, 129.9, 128.6, 127.2, 126.5, 124.3, 124.1, 123.8, 123.3, 123.1, 122.3, 121.4, 121.1, 120.8, 120.7, 119.0, 118.2, 117.9, 111.4, 104.8, 46.4, 31.9, 27.9, 27.6; HRMS (ESI) m / z: [M + H] + calculated for C 35 H 29 ClN3O2S2, 622.1384; found, 622.1381。

[0026] Example ④ 10-(benzo[b]thiophen-2-ylmethyl)-5-(1H-indol-3-yl)-8-(thiophen-2-ylsulfonyl)-1,2,3,4,5,8-hexa hydroazepino[2,3-e]indole: White solid; 109.2mg, 92% yield; mp 140‒142 °C; Rf = 0.20 (petroleum ether / acetone = 4 / 1);eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1 then 5 / 1 / 1; 1 H NMR (500 MHz, CDCl3):δ 7.93 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.69–7.63 (m, 2H), 7.52 (dd, J =4.9, 1.4 Hz, 1H), 7.45–7.40 (m, 2H), 7.38 (d, J = 8.6 Hz, 1H), 7.36–7.28 (m,3H), 7.18 (t, J = 7.5 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 7.00 (s, 1H), 6.99–6.96 (m, 1H), 6.94 (d, J = 8.6 Hz, 1H), 6.89 (d, J = 2.3 Hz, 1H), 4.54 (dd, J= 7.7, 3.6 Hz, 1H), 4.42 (s, 2H), 4.26 (s, 1H), 2.79 (dt, J = 12.8, 5.1 Hz,1H), 2.58 (dt, J = 12.3, 5.3 Hz, 1H), 2.17–2.05 (m, 2H), 1.67–1.58 (m, 2H); 1313C NMR (126 MHz, CDCl3): δ 143.7, 143.3, 140.1, 139.8, 138.1, 136.6, 135.5, 133.5, 133.3, 131.4, 128.2, 127.5, 127.1, 124.5, 124.2, 124.1, 123.3, 122.9, 122.4, 122.0, 121.9, 121.5, 120.0, 119.8, 119.2, 111.2, 106.3, 47.6, 41.0, 32.2, 29.2, 28.5; HRMS (ESI) m / z: [M + H] + calculated for C 33 H 28 N3O2S3, 594.1338; found, 594.1339.

[0027] Example 5 4-((10-(benzo[b]thiophen-2-ylmethyl)-5-(1H-indol-3-yl)-2,3,4,5-tetrahydroazepino[2,3-e]indol 8(1H)-yl)sulfonyl)morpholine: White solid; 109.0 mg, 91% yield; mp 158‒160 °C; Rf = 0.35 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1 then 5 / 1 / 1; 11H NMR (500 MHz, DMSO-d6): δ 10.82 (d, J = 2.4 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.80–7.74 (m, 1H), 7.52 (s, 1H), 7.36–7.31 (m, 2H), 7.27 (td, J = 7.3, 1.3 Hz, 2H), 7.22 (d, J = 8.0 Hz, 1H), 7.15 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 2.4 Hz, 1H), 7.03 (ddd, J = 8.2, 6.8, 1.1 Hz, 1H), 6.86 (t, J = 7.4 Hz, 1H), 6.73 (d, J = 8.7 Hz, 1H), 4.67 (d, J = 17.2 Hz, 1H), 4.63–4.52 (m, 2H), 4.46 (dd, J = 8.4, 3.3 Hz, 1H), 3.52 (dd, J = 5.9, 3.6 Hz, 4H), 3.12 (dd, J = 5.6, 3.9 Hz, 4H), 2.84 (dt, J = 11.7, 5.1 Hz, 1H), 2.56–2.51 (m, 1H), 2.06–1.95 (m, 2H), 1.60–1.51 (m, 2H); 13 13C NMR (126 MHz, DMSO-d6): δ 145.2, 143.0, 139.9, 138.9, 136.5, 135.4, 130.1, 126.8, 126.6, 125.1, 124.4, 123.8, 123.3, 123.2, 122.3, 121.3, 120.7, 120.5, 119.1, 118.2, 118.0, 117.7, 111.4, 105.2, 65.1, 46.6, 46.5, 32.0, 28.0, 27.7; HRMS (ESI) m / z: [M + H] + calculated for C 33 H 33 N4O3S2, 597.1989; found,

[0028] Example 6 5-(1H-indol-3-yl)-10-((5-methylbenzo[b]thiophen-2-yl)methyl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 112.0 mg, 91% yield;mp 194‒197 °C; Rf = 0.25 (petroleum ether / EtOAc = 5 / 1, twice); eluent:petroleum ether / EtOAc = 5 / 1; 1 H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H), 7.76(d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.2 Hz, 1H), 7.44–7.38 (m, 3H), 7.35 (d, J= 8.1 Hz, 1H), 7.31 (d, J = 8.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.16 (t, J= 7.6 Hz, 1H), 7.12 (dd, J = 8.3, 1.6 Hz, 1H), 7.01 (t, J = 7.5 Hz, 1H),6.92–6.85 (m, 3H), 4.51 (dd, J = 8.0, 3.3 Hz, 1H), 4.39 (s, 2H), 4.23 (s,1H), 2.75 (dt, J = 12.8, 5.1 Hz, 1H), 2.55 (dt, J = 12.3, 5.3 Hz, 1H), 2.44(s, 3H), 2.38 (s, 3H), 2.14–2.01 (m, 2H), 1.64–1.58 (m, 2H); 1313C NMR (126 MHz, CDCl3): δ 144.8, 143.6, 140.5, 136.9, 136.6, 135.6, 135.4, 134.2, 130.9, 130.0, 128.0, 127.2, 127.1, 125.9, 124.3, 123.3, 122.9, 122.0, 121.9, 121.7, 121.5, 120.1, 120.0, 119.2, 118.9, 111.2, 106.1, 47.7, 41.1, 32.2, 29.2, 28.6, 21.8, 21.5; HRMS (ESI) m / z: [M + H] + calcd for C 37 H 34 N3O2S2, 616.2087; found, 616.2087。

[0029] Example 7 10-((5-chlorobenzo[b]thiophen-2-yl)methyl)-5-(1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 103.0 mg, 81% yield; mp 209‒212 °C; Rf = 0.23 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc = 15 / 1 then 10 / 1; 11H NMR (500 MHz, DMSO-d6): δ 10.82 (d, J = 2.4 Hz, 1H), 7.87 (d, J = 8.6 Hz, 1H), 7.84 (d, J = 2.1 Hz, 1H), 7.79 (d, J = 8.1 Hz, 2H), 7.69 (s, 1H), 7.41 – 7.33 (m, 3H), 7.29 (dd, J = 8.6, 2.1 Hz, 1H), 7.23–7.15 (m, 3H), 7.07–7.00 (m, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 8.6 Hz, 1H), 4.66 (d, J = 17.2 Hz, 1H), 4.57 (d, J = 17.2 Hz, 1H), 4.50 (d, J = 3.9 Hz, 1H), 4.40 (dd, J = 7.9, 3.9 Hz, 1H), 2.78 (dq, J = 14.0, 4.8 Hz, 1H), 2.47–2.39 (m, 1H), 2.32 (s, 3H), 1.95 (tt, J = 10.0, 5.5 Hz, 2H), 1.50 (h, J = 6.9, 6.2 Hz, 2H); 13 13C NMR (126 MHz, DMSO d6): δ 147.4, 145.2, 143.0, 141.1, 137.3, 136.4, 134.7, 134.1, 131.0, 130.1, 129.4, 127.0, 126.7, 126.5, 124.3, 123.9, 123.8, 123.3, 122.4, 121.0, 120.8, 120.7, 119.7, 119.0, 118.1, 117.9, 111.4, 104.8, 46.4, 31.9, 27.9, 27.7, 21.0; HRMS (ESI) m / z: [M + H] + calcd for C 36 H 31 ClN3O2S2, 636.1541; found, 636.1541。

[0030] Example 8 10-((5-bromobenzo[b]thiophen-2-yl)methyl)-5-(1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: Light yellow solid; 115.7 mg, 85%yield; mp 159‒161°C; Rf = 0.23 (petroleum ether / EtOAc = 3 / 1); eluent:petroleum ether / EtOAc = 5 / 1; 1 H NMR (500 MHz, DMSO-d6): δ 10.82 (s, 1H), 7.98(s, 1H), 7.84–7.75 (m, 3H), 7.69 (s, 1H), 7.42–7.33 (m, 4H), 7.21–7.13 (m,3H), 7.04 (d, J = 6.4 Hz, 2H), 6.85 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 8.6 Hz,1H), 4.67 (d, J = 17.2 Hz, 1H), 4.57 (d, J = 17.3 Hz, 1H), 4.50 (d, J = 3.9Hz, 1H), 4.40 (dd, J = 8.0, 3.8 Hz, 1H), 2.78 (h, J = 4.4 Hz, 1H), 2.44 (dt,J = 13.7, 6.3 Hz, 1H), 2.31 (s, 3H), 2.00–1.88 (m, 2H), 1.50 (p, J = 5.9 Hz,2H); 13 C NMR (126 MHz, DMSO-d6): δ 147.3, 145.2, 143.0, 141.6, 137.8, 136.4,134.7, 134.1, 131.0, 130.1, 127.0, 126.7, 126.5, 126.4, 125.4, 124.3, 124.2,123.3, 121.0, 120.7, 120.6, 119.7, 119.0, 118.1, 117.9, 117.6, 111.4, 104.8,46.4, 31.9, 27.9, 27.7, 21.0; HRMS (ESI) m / z: [M + H] + calcd for C36 H 31 BrN3O2S2, 680.1036; found, 680.1036。

[0031] Example 9 10-(benzo[b]thiophen-2-ylmethyl)-5-(5-methoxy-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indol: White solid; 107.4 mg, 85% yield; mp 160‒162 °C; Rf = 0.25 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 1 1H NMR (500 MHz, CDCl3): δ 7.82 (s, 1H), 7.75 (t, J = 8.0 Hz, 3H), 7.62 (d, J = 7.7 Hz, 1H), 7.43 (s, 1H), 7.33–7.20 (m, 6H), 6.97 (s, 1H), 6.90–6.86 (m, 2H), 6.83–6.77 (m, 2H), 4.43 (d, J = 5.8 Hz, 1H), 4.40 (s, 2H), 4.21 (s, 1H), 3.73–3.67 (m, 3H), 2.79 2.70 (m, 1H), 2.54 (q, J = 9.8, 7.6 Hz, 1H), 2.36 (s, 3H), 2.06 (q, J = 5.9 Hz, 2H), 1.61 (t, J = 5.6 Hz, 2H); 1313C NMR (126 MHz, CDCl3): δ 153.8, 144.9, 143.6, 143.6, 140.1, 139.8, 135.6, 135.4, 131.8, 130.9, 130.0, 128.0, 127.5, 127.1, 124.5, 124.4, 124.2, 123.7, 123.3, 122.4, 121.9, 121.5, 119.6, 118.8, 112.0, 111.8, 106.2, 102.0, 56.0, 47.7, 41.1, 32.2, 29.2, 28.6, 21.7; HRMS (ESI) m / z: [M + H] + calcd for C 37 H 34 N3O3S2, 632.2036; found, 632.2037。

[0032] Example 10 10-(benzo[b]thiophen-2-ylmethyl)-5-(4-methyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 87.4 mg, 71% yield; mp 194‒196 °C; Rf = 0.22 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 11H NMR (500 MHz, CDCl3): δ 8.03 (d, J = 2.5 Hz, 1H), 7.79–7.75 (m, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.63 (dd, J = 7.5, 1.5 Hz, 1H), 7.42 (s, 1H), 7.36–7.28 (m, 3H), 7.23–7.19 (m, 3H), 7.10 (d, J = 2.4 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.94 (s, 1H), 6.71 (d, J = 7.1 Hz, 1H), 6.63 (d, J = 8.7 Hz, 1H), 4.72 (dd, J = 10.3, 2.3 Hz, 1H), 4.42 (s, 2H), 4.18 (s, 1H), 2.97–2.88 (m, 1H), 2.40–2.33 (m, 4H), 2.26–2.19 (m, 1H), 2.04 (s, 3H), 1.80 (dddd, J = 12.7, 10.2, 8.2, 4.9 Hz, 1H), 1.74–1.62 (m, 2H); 13 13C NMR (126 MHz, CDCl3): δ

这里缺少具体数值

这里缺少具体数值

[0033] Example 11 说明:原文中13C NMR和HRMS部分的具体数值缺失,翻译时保留了原文格式。请补充完整相关数值后,可进一步完善译文。10-(benzo[b]thiophen-2-ylmethyl)-5-(5-methyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 112.1 mg, 91% yield;mp 214‒216 °C; Rf = 0.32 (petroleum ether / acetone = 4 / 1); eluent: petroleumether / EtOAc / DCM = 7 / 1 / 1; 1 H NMR (500 MHz, CDCl3): δ 7.83 (s, 1H), 7.79–7.74(m, 3H), 7.64 (d, J = 7.5 Hz, 1H), 7.45 (s, 1H), 7.35–7.27 (m, 3H), 7.25–7.19(m, 4H), 7.02–6.97 (m, 2H), 6.89 (d, J = 8.7 Hz, 1H), 6.86 (d, J = 2.3 Hz,1H), 4.48 (dd, J = 7.3, 4.0 Hz, 1H), 4.42 (s, 2H), 4.23 (s, 1H), 2.77 (dt, J= 12.8, 5.1 Hz, 1H), 2.55 (dt, J = 12.3, 5.4 Hz, 1H), 2.37 (s, 6H), 2.13–2.02(m, 2H), 1.66–1.58 (m, 2H); 13 C NMR (126 MHz, CDCl3): δ 144.9, 143.6, 143.5,140.1, 139.8, 135.5, 135.4, 134.9, 131.1, 129.9, 128.4, 128.0, 127.3, 127.1,124.5, 124.3, 124.2, 123.5, 123.3, 123.0, 122.4, 121.9, 121.5, 119.6, 119.4,118.8, 110.9, 106.1, 47.6, 41.0, 32.4, 29.2, 28.7, 21.7, 21.6; HRMS (ESI) m / z: [M + H] + calcd for C 37 H 34N3O2S2, 616.2087; found, 616.2087。

[0034] Example 12 10-(benzo[b]thiophen-2-ylmethyl)-5-(7-methyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 113.3 mg, 92% yield; mp 164‒167 °C; Rf = 0.32 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 1 H NMR (500 MHz, CDCl3): δ 7.82 (s, 1H), 7.76–7.72(m, 3H), 7.62 (d, J = 7.6 Hz, 1H), 7.42 (s, 1H), 7.32–7.19 (m, 6H), 6.97–6.91(m, 3H), 6.89–6.84 (m, 2H), 4.48 (dd, J = 7.9, 3.3 Hz, 1H), 4.39 (s, 2H),4.20 (s, 1H), 2.74 (dt, J = 12.8, 5.1 Hz, 1H), 2.54 (ddd, J = 12.3, 9.1, 5.0Hz, 1H), 2.45 (s, 3H), 2.35 (s, 3H), 2.12–2.01 (m, 2H), 1.59 (p, J = 5.9 Hz,2H); 1313C NMR (126 MHz, CDCl3): δ 144.9, 143.6, 143.5, 140.1, 139.8, 136.2, 135.6, 135.3, 131.0, 130.0, 128.0, 127.1, 126.6, 124.5, 124.3, 124.2, 123.3, 122.6, 122.5, 122.4, 122.0, 121.4, 120.4, 120.3, 119.5, 118.8, 117.8, 106.1, 47.6, 41.1, 32.2, 29.2, 28.6, 21.7, 16.7; HRMS (ESI) m / z: [M + H] + calcd for C 37 H 34 N3O2S2, 616.2087; found, 616.2086。

[0035] Example 13 10-(benzo[b]thiophen-2-ylmethyl)-5-(1-methyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 104.6 mg, 85% yield; mp 154‒156 °C; Rf = 0.35 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc = 7 / 1 then 5 / 1; 11H NMR (500 MHz, CDCl3): δ 7.81–7.70 (m, 3H), 7.61 (d, J = 7.7 Hz, 1H), 7.42 (s, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.34–7.24 (m, 4H), 7.22–7.15 (m, 3H), 6.99 (t, J = 7.5 Hz, 1H), 6.96 (s, 1H), 6.89 (d, J = 8.6 Hz, 1H), 6.73 (s, 1H), 4.49 (dd, J = 8.4, 2.8 Hz, 1H), 4.39 (s, 2H), 4.20 (s, 1H), 3.65 (s, 3H), 2.72 (ddd, J = 12.8, 6.7, 3.7 Hz, 1H), 2.56 (ddd, J = 12.4, 8.0, 3.6 Hz, 1H), 2.34 (s, 3H), 2.13–2.00 (m, 2H), 1.62–1.54 (m, 2H); 13 13C NMR (126 MHz, CDCl3): δ 144.8, 143.6, 143.5, 140.1, 139.8, 137.3, 135.6, 135.4, 131.0, 129.9, 128.2, 127.7, 127.5, 127.1, 124.5, 124.3, 124.2, 123.3, 122.4, 121.9, 121.5, 121.4, 120.0, 118.9, 118.6, 118.2, 109.2, 106.1, 47.7, 41.2, 32.7, 32.3, 29.2, 28.4, 21.7; HRMS (ESI) m / z: [M + H] + calcd for C37H34N3O2S2, 616.2087; found, 616.2088。

[0036] Example 14 10-(benzo[b]thiophen-2-ylmethyl)-5-(5-fluoro-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 109.0 mg, 88% yield;mp 160‒162°C; Rf = 0.28 (petroleum ether / acetone = 4 / 1); eluent: petroleumether / EtOAc / DCM = 7 / 1 / 1; 1 H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H), 7.81–7.72(m, 3H), 7.66–7.61 (m, 1H), 7.44 (s, 1H), 7.36–7.27 (m, 3H), 7.26–7.21 (m,3H), 7.02–6.93 (m, 3H), 6.90 (td, J = 9.0, 2.5 Hz, 1H), 6.84 (d, J = 8.6 Hz,1H), 4.47–4.35 (m, 3H), 4.20 (s, 1H), 2.75 (dt, J = 12.7, 5.3 Hz, 1H), 2.54(dt, J = 12.4, 5.7 Hz, 1H), 2.38 (s, 3H), 2.05 (q, J = 5.9 Hz, 2H), 1.64 1.56(m, 2H); 1313C NMR (126 MHz, CDCl3): δ 157.7 (d, J = 234.6 Hz), 144.9, 143.6, 143.5, 140.1, 139.8, 135.7, 135.3, 133.1, 130.6, 130.0, 127.8, 127.5 (d, J = 9.7 Hz), 127.1, 124.7, 124.6, 124.5, 124.2, 123.3, 122.4, 122.0, 121.5, 120.1 (d, J = 4.7 Hz), 118.9, 111.7 (d, J = 9.7 Hz), 110.3 (d, J = 26.5 Hz), 106.2, 104.9 (d, J = 23.3 Hz), 47.6, 41.0, 32.0, 29.2, 28.4, 21.7; 19F NMR (470 MHz, CDCl3) δ −124.86; HRMS (ESI) m / z: [M + H] + calcd for C 36 H 31 FN3O2S2, 620.1836; found, 620.1837。

[0037] Example 15 10-(benzo[b]thiophen-2-ylmethyl)-5-(5-chloro-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 113.2 mg, 89% yield; mp 152−154 °C; Rf = 0.31 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 11H NMR (500 MHz, CDCl3): δ 7.95 (s, 1H), 7.78–7.72 (m, 3H), 7.62 (d, J = 7.7 Hz, 1H), 7.43 (s, 1H), 7.34–7.21 (m, 7H), 7.10–7.06 (m, 1H), 6.96 (s, 1H), 6.90 (s, 1H), 6.81 (d, J = 8.5 Hz, 1H), 4.43 (t, J = 5.7 Hz, 1H), 4.39 (s, 2H), 4.19 (s, 1H), 2.73 (dt, J = 11.6, 5.3 Hz, 1H), 2.53 (dt, J = 12.5, 5.7 Hz, 1H), 2.36 (s, 3H), 2.07–1.98 (m, 2H), 1.60–1.56 (m, 2H); 13 13C NMR (126 MHz, CDCl3): δ 144.9, 143.6, 143.5, 140.1, 139.8, 135.7, 135.3, 134.9, 130.6, 130.0, 128.2, 127.8, 127.1, 125.0, 124.6, 124.5, 124.3, 124.2, 123.3, 122.4, 122.2, 122.0, 121.6, 119.6, 119.4, 118.8, 112.2, 106.2, 47.6, 40.9, 32.1, 29.2, 28.4, 21.7; HRMS (ESI) m / z: [M + H] + calculated for C 36 H 31 ClN3O2S2, 636.1541; found, 636.1542。

[0038] Example 16 10-(benzo[b]thiophen-2-ylmethyl)-5-(5-bromo-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 113.0 mg, 83% yield;mp 145‒147 °C; Rf = 0.30 (petroleum ether / acetone = 4 / 1); eluent: petroleumether / EtOAc / DCM = 7 / 1 / 1; 1 H NMR (500 MHz, CDCl3): δ 7.95 (s, 1H), 7.78–7.73(m, 3H), 7.63 (d, J = 7.6 Hz, 1H), 7.50 (s, 1H), 7.43 (s, 1H), 7.35–7.27 (m,3H), 7.23–7.18 (m, 4H), 6.96 (s, 1H), 6.90 (s, 1H), 6.82 (d, J = 8.5 Hz, 1H),4.46–4.42 (m, 1H), 4.40 (s, 2H), 4.20 (s, 1H), 2.76–2.68 (m, 1H), 2.53 (dt, J= 12.7, 5.6 Hz, 1H), 2.37 (s, 3H), 2.08–1.98 (m, 2H), 1.62–1.56 (m, 2H); 13 CNMR (126 MHz, CDCl3): δ 144.9, 143.6, 143.5, 140.1, 139.8, 135.7, 135.34,135.21, 130.5, 130.0, 128.9, 127.9, 127.1, 124.8, 124.6, 124.5, 124.2, 123.3,122.5, 122.4, 122.0, 121.6, 119.6, 118.8, 112.6, 106.3, 47.6, 41.0, 32.2,29.2, 28.4, 21.8; HRMS (ESI) m / z: [M + H] + calcd for C 36 H 31 BrN3O2S2, 680.1036;found, 680.1036。

[0039] Example 17 10-(benzo[b]thiophen-2-ylmethyl)-5-(6-chloro-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 108.1 mg, 85% yield; mp 164‒166 °C; Rf = 0.32 (petroleum ether / acetone = 4 / 1); eluent: S11 petroleum ether / EtOAc / DCM = 7 / 1 / 1; 1 1H NMR (500 MHz, CDCl3): δ 7.91 (s, 1H), 7.78–7.74 (m, 3H), 7.63 (dd, J = 7.3, 1.4 Hz, 1H), 7.45 (s, 1H), 7.34–7.27 (m, 4H), 7.25–7.21 (m, 3H), 6.97 (s, 1H), 6.95 (dd, J = 8.5, 1.9 Hz, 1H), 6.88 (d, J = 2.2 Hz, 1H), 6.82 (d, J = 8.6 Hz, 1H), 4.46 (t, J = 5.6 Hz, 1H), 4.40 (s, 2H), 4.20 (s, 1H), 2.75 (dt, J = 12.8, 5.2 Hz, 1H), 2.54 (dt, J = 12.3, 5.7 Hz, 1H), 2.38 (s, 3H), 2.04 (q, J = 5.9 Hz, 2H), 1.59 (p, J = 5.6 Hz, 2H); 1313C NMR (126 MHz, CDCl3): δ 144.9, 143.6, 143.5, 140.1, 139.8, 136.9, 135.6, 135.3, 130.6, 130.0, 127.8, 127.2, 125.7, 124.6, 124.5, 124.2, 123.5, 123.3, 122.4, 122.0, 121.5, 120.9, 120.03, 119.98, 118.8, 111.1, 106.2, 47.6, 40.9, 32.1, 29.2, 28.4, 21.8; HRMS (ESI) m / z: [M + H] + calcd for C 36 H 31 ClN3O2S2, 636.1541; found, 636.1542。

[0040] Example 18 methyl 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol 5-yl)-1H-indole-5-carboxylate: White solid; 67.3.0 mg, 51% yield; mp 189‒191 °C; Rf = 0.20 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc = 10 / 1, then 5 / 1; 11H NMR (500 MHz, CDCl3): δ 8.24 (d, J = 1.5 Hz, 1H), 8.13 (s, 1H), 7.87 (dd, J = 8.5, 1.6 Hz, 1H), 7.80–7.74 (m, 3H), 7.63 (dd, J = 7.6, 1.4 Hz, 1H), 7.45 (s, 1H), 7.35–7.30 (m, 3H), 7.28 (td, J = 7.6, 1.5 Hz, 1H), 7.24 (d, J = 8.1 Hz, 2H), 6.97 (s, 1H), 6.92 (d, J = 2.3 Hz, 1H), 6.87 (d, J = 8.6 Hz, 1H), 4.55 (dd, J = 8.5, 2.4 Hz, 1H), 4.41 (s, 2H), 4.23 (s, 1H), 3.88 (s, 3H), 2.70 (dt, J = 12.8, 5.3 Hz, 1H), 2.59 (dt, J = 12.3, 5.7 Hz, 1H), 2.37 (s, 3H), 2.17 (ddt, J = 13.8, 8.3, 5.7 Hz, 1H), 2.06–1.99 (m, 1H), 1.58–1.55 (m, 2H); 13 13C NMR (126 MHz, CDCl3): δ 168.3, 144.9, 143.7, 143.5, 140.1, 139.8, 139.2, 135.7, 135.4, 130.6, 130.0, 128.1, 127.1, 126.7, 124.6, 124.5, 124.2, 123.4, 123.3, 122.8, 122.4, 122.0, 121.6, 121.5, 121.1, 118.7, 110.9, 106.2, 51.9, 47.7, 41.4, 32.4, 29.2, 28.3, 21.8; HRMS (ESI) m / z: [M + H] + calculated for C 38 H 34 N3O4S2, 660.1985; found, 660.1985。

[0041] Example 19 10-(benzo[b]thiophen-2-ylmethyl)-5-(2-methyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 117.0 mg, 95% yield;mp 213‒215 °C; Rf = 0.30 (petroleum ether / acetone = 4 / 1); eluent: petroleumether / EtOAc / DCM = 7 / 1 / 1; 1 H NMR (500 MHz, CDCl3): δ 7.84–7.73 (m, 4H), 7.68–7.63 (m, 1H), 7.48–7.43 (m, 2H), 7.35–7.26 (m, 4H), 7.22 (d, J = 8.1 Hz, 2H),7.12 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.03–6.98 (m, 2H), 6.84 (d, J = 8.7 Hz,1H), 4.42 (s, 2H), 4.36–4.12 (m, 2H), 2.99 (dt, J = 12.8, 4.1 Hz, 1H), 2.43–2.34 (m, 4H), 2.23 (s, 3H), 2.14–2.03 (m, 2H), 1.78–1.67 (m, 2H); 13 C NMR (126MHz, CDCl3): δ 144.8, 143.6, 143.3, 140.2, 139.8, 135.6, 135.4, 135.3, 132.3,130.9, 130.0, 128.6, 127.2, 126.9, 124.5, 124.4, 124.2, 123.3, 122.4, 122.0,121.6, 120.9, 120.2, 119.1, 118.6, 116.3, 110.4, 106.2, 47.5, 39.8, 34.0,31.2, 29.1, 21.7, 12.4; HRMS (ESI) m / z: [M + H] + calcd for C 37 H 34 N3O2S2,616.2087; found, 616.2087。

[0042] Example 20 10-(benzo[b]thiophen-2-ylmethyl)-5-(2-phenyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydro azepino[2,3-e]indole: White solid; 120.7 mg, 89% yield; mp 147‒149 °C; Rf = 0.22 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 1 1H NMR (500 MHz, CDCl3): δ 8.04 (s, 1H), 7.79–7.71 (m, 3H), 7.63 (dd, J = 7.3, 1.3 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.33–7.18 (m, 11H), 7.07–7.01 (m, 2H), 6.97 (s, 1H), 4.43 (dd, J = 10.8, 1.6 Hz, 1H), 4.40 (s, 2H), 4.21 (s, 1H), 2.90 (dt, J = 12.9, 4.1 Hz, 1H), 2.35 (s, 3H), 2.30 (ddd, J = 13.2, 10.3, 3.3 Hz, 1H), 2.14 (q, J = 12.0, 10.7 Hz, 1H), 2.07–1.98 (m, 1H), 1.64–1.52 (m, 2H); 1313C NMR (126 MHz, CDCl3): δ 144.9, 143.5, 143.4, 140.2, 139.8, 136.5, 135.44, 135.38, 134.3, 133.2, 132.4, 130.0, 128.9, 128.8, 128.2, 127.7, 127.4, 127.2, 124.5, 124.4, 124.2, 123.3, 122.4, 122.2, 122.0, 121.9, 121.7, 119.5, 118.8, 117.7, 111.1, 106.3, 47.4, 40.4, 34.1, 31.1, 29.2, 21.7; HRMS (ESI) m / z: [M + H] + calcd for C 42 H 36 N3O2S2, 678.2243; found, 678.2244。

[0043] Example 21 10-(benzo[b]thiophen-2-ylmethyl)-5-(5-methoxy-2-methyl-1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8 hexahydroazepino[2,3-e]indole: White solid; 117.5 mg, 91% yield; mp 154‒157 °C; Rf = 0.25 (petroleum ether / acetone = 4 / 1); eluent: petroleum ether / EtOAc / DCM = 15 / 1 / 1; 11H NMR (500 MHz, CDCl3): δ 7.78–7.74 (m, 3H), 7.69 (s, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.45 (s, 1H), 7.35–7.27 (m, 3H), 7.22 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.7 Hz, 1H), 7.01 (s, 1H), 6.90 (d, J = 2.4 Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 6.77 (dd, J = 8.7, 2.4 Hz, 1H), 4.42 (s, 2H), 4.35–4.15 (m, 2H), 3.73 (s, 3H), 3.00 (dt, J = 13.0, 4.1 Hz, 1H), 2.44–2.35 (m, 4H), 2.21 (s, 3H), 2.12–2.00 (m, 2H), 1.76–1.68 (m, 2H); 13 13C NMR(126 MHz, CDCl3): δ 153.7, 144.9, 143.7, 143.3, 140.2, 139.8, 135.4, 135.3, 132.2, 131.9, 130.7, 130.0, 129.0, 127.2, 127.0, 124.5, 124.4, 124.2, 123.3, 122.4, 122.0, 121.7, 118.6, 116.3, 110.9, 110.4, 106.3, 102.8, 56.1, 47.5, 39.8, 33.9, 31.2, 29.1, 21.7, 12.6; HRMS (ESI) m / z: [M + H] + calculated for C 38 H 36 N3O3S2, 646.2193; found, 646.2193。

[0044] Example 22 10-(benzofuran-2-ylmethyl)-5-(1H-indol-3-yl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indole: white solid; 107.8 mg ,92% yield. mp 154‒157 °C; 1 H NMR (500 MHz, CDCl3): δ 7.95 (s, 1H), 7.76 (d, J = 8.1 Hz, 2H), 7.46(dd, J = 7.8, 5.6 Hz, 2H), 7.42 (t, J = 4.0 Hz, 2H), 7.36 (d, J = 8.1 Hz,1H), 7.33 (d, J = 8.6 Hz, 1H), 7.28–7.25 (m, 1H), 7.24–7.15 (m, 4H), 7.03 (t,J = 7.5 Hz, 1H), 6.93 (d, J = 2.1 Hz, 1H), 6.89 (d, J = 8.6 Hz, 1H), 6.34 (s,1H), 4.56 (dd, J = 7.2, 4.0 Hz, 1H), 4.45–4.07 (m, 3H), 2.92 (dt, J = 12.8,5.1 Hz, 1H), 2.73 (dt, J = 12.3, 5.7 Hz, 1H), 2.36 (s, 3H), 2.20–2.06 (m,2H), 1.68 (p, J = 5.7 Hz, 2H); 13 C NMR (126 MHz, CDCl3): δ 156.3, 155.1,144.9, 143.4, 136.6, 135.41, 135.36, 131.1, 130.0, 128.7, 127.9, 127.14,127.11, 124.5, 124.0, 123.0, 122.9, 121.9, 121.5, 120.8, 120.0, 119.9, 119.2,116.6, 111.2, 111.1, 106.2, 104.2, 48.0, 41.0, 32.2, 28.6, 27.4, 21.7; HRMS(ESI-TOF) m / z: [M + H] + calcd for C 36 H 32N3O3S, 586.2159; found, 586.2160。

[0045] Example 23 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 3,6-dichloro-2-methoxybenzoate: White solid; 146.1 mg, 89% yield; mp 142‒146 °C; Rf = 0.20(petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc / DCM = 5 / 1 / 1; 1 HNMR (500 MHz, CDCl3): δ 8.01 (s, 1H), 7.80–7.73 (m, 3H), 7.65–7.61 (m, 1H),7.44 (s, 1H), 7.40 (d, J = 8.7 Hz, 1H), 7.37–7.30 (m, 3H), 7.28 (td, J = 7.5,1.5 Hz, 1H), 7.25 (d, J = 2.3 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.16 (d, J =8.7 Hz, 1H), 7.07 (dd, J = 8.7, 2.2 Hz, 1H), 6.98 (s, 1H), 6.92–6.87 (m, 2H),4.50 (dd, J = 7.9, 3.0 Hz, 1H), 4.42 (s, 2H), 4.23 (s, 1H), 3.92 (s, 3H),2.71 (dt, J = 12.8, 5.2 Hz, 1H), 2.63–2.53 (m, 1H), 2.32 (s, 3H), 2.12 2.00(m, 2H), 1.59 (p, J = 6.1 Hz, 2H); 1313C NMR (126 MHz, CDCl3): δ 164.1, 154.1, 144.9, 143.9, 143.7, 143.5, 140.1, 139.8, 135.6, 135.3, 134.7, 132.1, 130.5, 130.4, 130.0, 129.9, 128.2, 127.4, 127.1, 126.9, 126.0, 124.8, 124.5, 124.4, 124.2, 123.3, 122.4, 121.9, 121.5, 120.1, 118.8, 115.7, 111.8, 111.73 106.2, 62.5, 47.7, 41.2, 32.1, 29.2, 28.3, 21.7; HRMS (ESI) m / z: [M + H] + calcd for C 44 H 36 Cl2N3O5S2, 820.1468; found, 820.1470。

[0046] Example 24 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl (2S)-2-(6-methoxynaphthalen-2-yl)propanoate: White solid; 137.8 mg, 83% yield; mp 152‒154 °C; Rf = 0.20 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc / DCM = 5 / 1 / 1, then 3 / 1 / 1; 1H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H), 7.81 7.72 (m, 5H), 7.69(d, J = 9.5 Hz, 1H), 7.63 (d, J = 7.7 Hz, 1H), 7.52 (dt, J = 8.4, 2.3 Hz,1H), 7.45 (s, 1H), 7.35–7.27 (m, 3H), 7.21 (d, J = 8.0 Hz, 2H), 7.18–7.08 (m,4H), 6.97 (s, 1H), 6.86 (t, J = 8.1 Hz, 1H), 6.78 (dd, J = 6.3, 2.3 Hz, 1H),6.73 (ddd, J = 8.8, 4.6, 2.2 Hz, 1H), 4.40 (s, 3H), 4.20 (s, 1H), 4.09 (qd, J= 7.2, 1.9 Hz, 1H), 3.92 (s, 3H), 2.69 (dq, J = 10.5, 5.1 Hz, 1H), 2.54 (dt,J = 12.5, 6.0 Hz, 1H), 2.33 (s, 3H), 2.06–1.92 (m, 2H), 1.70 (dd, J = 7.1,2.7 Hz, 3H), 1.53 (p, J = 6.0 Hz, 2H); 13 C NMR (126 MHz, CDCl3): δ 174.1,157.8, 144.9, 144.2, 143.63, 143.60, 143.5, 140.1, 139.7, 135.6, 135.5,135.3, 134.3, 133.9, 130.7, 130.0, 129.4, 129.1, 128.2, 128.1, 127.4, 127.21,127.18, 127.1, 126.4, 126.2, 124.52, 124.49, 124.46, 124.3, 124.2, 123.3,122.4, 121.9, 121.4, 119.9, 119.1, 118.8, 115.8, 111.6, 111.5, 106.1, 105.7,55.4, 47.6, 45.72, 45.70, 41.3, 41.1, 32.3, 32.1, 29.2, 28.3, 21.7, 18.8;HRMS (ESI) m / z: [M + H]+ Calculated for C 50 H 44 N3O5S2, 830.2717; found, 830.2717。

[0047] Example 25 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoate: White solid; 154.7 mg, 91% yield; mp 98‒101 °C; Rf = 0.25(petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1; 1HNMR (500 MHz, CDCl3) δ 8.08 (s, 1H), 7.79–7.74 (m, 2H), 7.73 (d, J = 7.8 Hz,1H), 7.64 (dd, J = 7.4, 1.4 Hz, 1H), 7.49 (s, 1H), 7.42 (d, J = 8.7 Hz, 1H),7.31 (td, J = 7.5, 1.3 Hz, 1H), 7.29–7.24 (m, 2H), 7.22 (d, J = 8.1 Hz, 2H),7.09 (d, J = 2.2 Hz, 1H), 7.05 (s, 1H), 6.96 (d, J = 7.5 Hz, 1H), 6.88 (d, J= 8.7 Hz, 1H), 6.84–6.79 (m, 2H), 6.64 (d, J = 7.5 Hz, 1H), 6.61 (d, J = 1.6Hz, 1H), 4.80 (s, 1H), 4.52–4.44 (m, 2H), 4.40 (d, J = 17.4 Hz, 1H), 3.95 (p,J = 2.8 Hz, 2H), 2.71 (ddd, J = 12.8, 6.6, 3.3 Hz, 1H), 2.42 (ddd, J = 12.4,9.2, 2.9 Hz, 1H), 2.34 (s, 3H), 2.29 (s, 3H), 2.13 (s, 3H), 2.00 (q, J = 6.0Hz, 2H), 1.90–1.83 (m, 4H), 1.70–1.61 (m, 1H), 1.59–1.50 (m, 1H), 1.35 (s,6H); 1313C NMR (126 MHz, CDCl3): δ 177.3, 157.1, 145.1, 144.4, 143.3, 140.1, 139.8, 136.6, 135.6, 135.2, 134.4, 131.8, 130.4, 130.1, 127.8, 127.20, 127.16, 125.1, 124.7, 124.4, 124.3, 123.7, 123.4, 122.4, 122.3, 121.8, 120.8, 119.3, 118.2, 116.2, 112.1, 111.70, 111.66, 108.0, 68.0, 47.8, 42.4, 40.6, 37.3, 32.2, 28.9, 28.0, 25.4, 25.35, 25.30, 21.7, 21.5, 15.9; HRMS (ESI) m / z: [M + H] + calcd for C 51 H 52 N3O5S2, 850.3343; found, 850.3343。

[0048] Example 26 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 2-(4-isobutylphenyl)propanoate: White solid; 143.4 mg, 89% yield; mp 94‒96 °C; Rf = 0.30 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc / DCM = 7 / 1 / 1, then 5 / 1 / 1; 1H NMR (500 MHz, CDCl3): δ 7.93 (s, 1H), 7.80 7.77 (m, 2H), 7.76(d, J = 7.8 Hz, 1H), 7.66–7.62 (m, 1H), 7.45 (s, 1H), 7.35–7.27 (m, 5H), 7.23(d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.7 Hz, 1H), 7.14 (dd, J = 8.1, 2.5 Hz,2H), 7.10 (dd, J = 12.3, 2.2 Hz, 1H), 6.98 (s, 1H), 6.87 (dd, J = 8.7, 7.0Hz, 1H), 6.78 (dd, J = 5.7, 2.2 Hz, 1H), 6.74 (ddd, J = 8.7, 4.0, 2.2 Hz,1H), 4.46–4.38 (m, 3H), 4.22 (s, 1H), 3.93 (qd, J = 7.1, 1.5 Hz, 1H), 2.69(dq, J = 12.8, 5.1 Hz, 1H), 2.59–2.52 (m, 1H), 2.48 (d, J = 7.1 Hz, 2H), 2.36(s, 3H), 2.08–1.95 (m, 2H), 1.88 (dp, J = 13.5, 6.7 Hz, 1H), 1.61 (dd, J =7.2, 2.6 Hz, 3H), 1.55 (p, J = 5.7 Hz, 2H), 0.93 (s, 3H), 0.92 (s, 3H); 13CNMR (126 MHz, CDCl3): δ 174.18, 174.17, 144.9, 144.2, 143.7, 143.6, 143.5,140.74, 140.73, 140.1, 139.8, 137.7, 137.6, 135.5, 135.3, 134.3, 130.69,130.68, 130.0, 129.6, 128.2, 128.1, 127.4, 127.20, 127.17, 127.1, 124.53,124.51, 124.47, 124.3, 124.2, 123.3, 122.4, 121.9, 121.44, 121.43, 119.9,119.8, 118.8, 115.8, 111.6, 111.5, 106.1, 47.6, 45.41, 45.39, 45.2, 41.3,41.2, 32.2, 32.1, 30.3, 29.2, 28.4, 22.5, 21.7, 18.85, 18.83; HRMS (ESI) m / z: [M + H] + calculated for C 49 H 48 N3O4S2, 806.3081; found, 806.3085。

[0049] Example 27 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 4-([1,1'-biphenyl]-4-yl)-4-oxobutanoate: White solid; 141.8 mg, 83% yield; mp 131‒133 °C; Rf = 0.20(petroleum ether / acetone = 4 / 1, twice); eluent: petroleum ether / EtOAc / DCM =5 / 1 / 1; 11H NMR (500 MHz, CDCl3): δ 8.10–8.06 (m, 2H), 7.96 (s, 1H), 7.79–7.73(m, 3H), 7.71–7.68 (m, 2H), 7.64–7.62 (m, 3H), 7.50–7.46 (m, 2H), 7.44 (s,1H), 7.42–7.39 (m, 1H), 7.34–7.26 (m, 4H), 7.23 (d, J = 8.1 Hz, 2H), 7.17 (d,J = 2.3 Hz, 1H), 6.97 (s, 1H), 6.92 (dd, J = 8.7, 2.2 Hz, 1H), 6.90–6.84 (m,2H), 4.45 (dd, J = 8.2, 2.7 Hz, 1H), 4.41 (s, 2H), 4.21 (s, 1H), 3.45 (t, J =6.7 Hz, 2H), 3.02 (t, J = 6.7 Hz, 2H), 2.71 (dt, J = 12.7, 5.2 Hz, 1H), 2.55(dt, J = 12.3, 5.7 Hz, 1H), 2.36 (s, 3H), 2.10–1.98 (m, 2H), 1.60–1.54 (m,2H); 13 13C NMR (126 MHz, CDCl3): δ 197.7, 172.5, 146.0, 144.9, 144.1, 143.5,140.1, 140.0, 139.8, 135.6, 135.4, 134.4, 130.7, 130.0, 129.1, 128.8, 128.4,128.1, 127.4, 127.3, 127.2, 124.5, 124.45, 124.37, 124.2, 123.3, 122.4,122.0, 121.5, 120.1, 118.8, 116.1, 111.8, 111.6, 106.2, 47.7, 41.2, 33.7,32.2, 29.2, 28.7, 28.4, 21.7; HRMS (ESI) m / z: [M + H] + calculated for C 52 H 44 N3O5S2, 854.2717; found, 854.2726。

[0050] Example 28 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 2-acetoxybenzoate: Whitesolid; 129.5 mg, 83% yield; mp 142‒144 °C; Rf = 0.15 (petroleum ether / acetone= 4 / 1, twice); eluent: petroleum ether / EtOAc / DCM = 3 / 1 / 1; 1 H NMR (500 MHz,CDCl3): δ 8.19 (dd, J = 7.9, 1.7 Hz, 1H), 8.05 (d, J = 2.4 Hz, 1H), 7.74 (d,J = 8.1 Hz, 2H), 7.72 (d, J = 7.6 Hz, 1H), 7.59 (td, J = 7.9, 1.6 Hz, 2H),7.41 (s, 1H), 7.35–7.23 (m, 5H), 7.20–7.16 (m, 3H), 7.14 (dd, J = 8.1, 1.1Hz, 1H), 6.94 (s, 1H), 6.91 (dd, J = 8.7, 2.2 Hz, 1H), 6.87–6.81 (m, 2H),4.44 (t, J = 5.4 Hz, 1H), 4.37 (s, 2H), 4.19 (s, 1H), 2.71 (dt, J = 12.5, 5.1Hz, 1H), 2.52 (dt, J = 12.3, 5.6 Hz, 1H), 2.29 (s, 3H), 2.22 (s, 3H), 2.04–1.96 (m, 2H), 1.59–1.51 (m, 2H); 1313C NMR (126 MHz, CDCl3): δ 170.0, 164.0, 151.2, 144.9, 143.8, 143.54, 143.51, 140.1, 139.7, 135.6, 135.3, 134.6, 134.4, 132.4, 130.6, 130.0, 128.0, 127.4, 127.1, 126.2, 124.6, 124.5, 124.3, 124.1, 124.0, 123.3, 123.1, 122.3, 121.9, 121.5, 120.0, 118.9, 115.9, 111.9, 111.8, 106.1, 47.6, 40.9, 32.1, 29.1, 28.4, 21.6, 21.1; HRMS (ESI) m / z: [M + H] + calcd for C 45 H 38 N3O6S2, 780.2197; found, 780.2197。

[0051] Example 29 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate: White solid; 162.8 mg, 85% yield; mp 175‒177 °C; Rf = 0.20 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc / DCM = 5 / 1 / 1; 1H NMR (500 MHz, CDCl3): δ 7.97 (s, 1H), 7.80–7.76 (m,2H), 7.75 (d, J = 7.7 Hz, 1H), 7.68–7.65 (m, 2H), 7.64–7.61 (m, 1H), 7.48–7.43 (m, 3H), 7.34–7.26 (m, 3H), 7.25–7.21 (m, 3H), 7.15 (d, J = 2.2 Hz, 1H),7.07 (d, J = 2.5 Hz, 1H), 6.97 (s, 1H), 6.91 (d, J = 9.0 Hz, 1H), 6.88–6.83(m, 2H), 6.82 (dd, J = 8.7, 2.2 Hz, 1H), 6.68 (dd, J = 9.0, 2.5 Hz, 1H),4.46–4.36 (m, 3H), 4.21 (s, 1H), 3.88 (s, 2H), 3.78 (s, 3H), 2.70 (dt, J =11.0, 5.0 Hz, 1H), 2.54 (dt, J = 12.4, 5.6 Hz, 1H), 2.43 (s, 3H), 2.35 (s,3H), 2.06–1.95 (m, 2H), 1.57–1.52 (q, J = 5.7 Hz, 2H); 13 C NMR (126 MHz,CDCl3): δ 170.3, 168.5, 156.2, 144.9, 144.1, 143.6, 143.5, 140.1, 139.8,139.4, 136.2, 135.6, 135.4, 134.4, 134.0, 131.3, 131.0, 130.8, 130.7, 130.0,129.2, 128.0, 127.3, 127.2, 124.6, 124.5, 124.4, 124.2, 123.3, 122.4, 121.9,121.5, 120.0, 118.7, 115.8, 115.1, 112.5, 112.0, 111.7, 111.6, 106.1, 101.3,55.8, 47.6, 41.2, 32.3, 30.7, 29.2, 28.4, 21.7, 13.7; HRMS (ESI) m / z: [M + H] + calcd for C 55 H46 ClN4O6S2, 957.2542; found, 957.2546。

[0052] Example 30 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 3-(4,5-diphenyloxazol-2-yl)propanoate: White solid; 159.0 mg, 89% yield; mp 157‒159 °C; Rf = 0.25(petroleum ether / EtOAc = 3 / 1, twice); eluent: petroleum ether / EtOAc / DCM = 5 / 1 / 1; 1 1H NMR (500 MHz, CDCl3): δ 7.99 (d, J = 2.4 Hz, 1H), 7.80–7.77 (m, 2H),7.75 (dd, J = 7.9, 1.3 Hz, 1H), 7.69–7.65 (m, 2H), 7.64–7.61 (m, 1H), 7.617.57 (m, 2H), 7.45 (s, 1H), 7.37–7.26 (m, 9H), 7.25–7.21 (m, 3H), 7.16 (d, J= 2.2 Hz, 1H), 6.98 6.96 (m, 1H), 6.90–6.85 (m, 2H), 6.83 (d, J = 2.3 Hz,1H), 4.44–4.39 (m, 3H), 4.21 (s, 1H), 3.34 3.28 (m, 2H), 3.17–3.11 (m, 2H),2.69 (dt, J = 12.6, 5.2 Hz, 1H), 2.54 (dt, J = 12.4, 5.9 Hz, 1H), 2.06–1.94(m, 2H), 1.54 (p, J = 5.5 Hz, 2H); 1313C NMR (126 MHz, CDCl3): δ 171.5, 161.8, 145.6, 144.9, 144.0, 143.6, 143.5, 140.1, 139.8, 135.6, 135.4, 135.3, 134.4, 132.6, 130.6, 130.0, 129.1, 128.8, 128.7, 128.6, 128.2, 128.1, 128.0, 127.3, 127.1, 126.6, 124.6, 124.5, 124.3, 124.2, 123.3, 122.4, 121.9, 121.5, 120.0, 118.8, 115.9, 111.7, 111.6, 106.1, 47.6, 41.2, 32.1, 31.4, 29.2, 28.3, 23.7, 21.7; HRMS (ESI) m / z: [M + H] + calculated for C 54 H 45 N4O5S2, 893.2826; found, 893.2825。

[0053] Example 31 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl ((1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate: White solid; 134.8 mg, 81% yield; mp 168‒170 °C; Rf = 0.19 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc / DCM = 5 / 1 / 1; 1H NMR (500 MHz, CDCl3): δ 8.10 (s, 1H),7.78–7.71 (m, 3H), 7.62 (d, J = 7.7 Hz, 1H), 7.42 (s, 1H), 7.33–7.24 (m, 5H),7.22 (d, J = 8.1 Hz, 2H), 7.07 (dd, J = 8.8, 2.3 Hz, 1H), 6.96 (d, J = 2.3Hz, 1H), 6.90 (d, J = 2.2 Hz, 1H), 6.83 (t, J = 8.6 Hz, 1H), 4.46 (d, J = 2.6Hz, 1H), 4.39 (s, 2H), 4.20 (s, 1H), 3.74 (dd, J = 17.1, 15.0 Hz, 1H), 3.13(dd, J = 15.0, 7.6 Hz, 1H), 2.70 (dt, J = 12.2, 4.3 Hz, 1H), 2.53 (ddd, J =22.3, 16.1, 9.2 Hz, 2H), 2.42–2.34 (m, 4H), 2.11–1.99 (m, 4H), 1.93 (dd, J =18.5, 4.1 Hz, 1H), 1.68 (ddd, J = 14.1, 9.3, 4.7 Hz, 1H), 1.56 (p, J = 6.0Hz, 2H), 1.41 (ddt, J = 9.4, 7.4, 3.7 Hz, 1H), 1.09 (d, J = 11.6 Hz, 3H),0.83 (d, J = 10.8 Hz, 3H); 1313C NMR (126 MHz, CDCl3): δ 214.4, 214.3, 146.0, 145.0, 143.6, 143.5, 142.8, 140.1, 139.7, 135.7, 135.3, 135.0, 130.5, 130.0, 129.0, 128.0, 127.3, 127.1, 125.1, 124.5, 124.4, 124.2, 123.3, 122.4, 121.9, 121.5, 120.2, 118.93, 118.92, 116.3, 116.2, 112.9, 112.8, 112.0, 106.1, 58.22, 58.20, 48.02, 48.00, 47.6, 46.9, 46.8, 43.0, 42.58, 42.56, 41.12, 41.06, 32.1, 32.0, 29.2, 28.3, 27.0, 25.2, 21.7, 20.1, 20.0, 19.8, 19.7; HRMS (ESI) m / z: [M + H] + calculated for C 46 H 46 N3O6S3, 832.2543; found, 832.2558。

[0054] Example 32 3-(10-(benzo[b]thiophen-2-ylmethyl)-8-tosyl-1,2,3,4,5,8-hexahydroazepino[2,3-e]indol-5-yl)-1H indol-5-yl 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin-3-yl)acetate: White solid; 151.0 mg, 87% yield; mp 164‒167 °C; Rf = 0.20 (petroleum ether / EtOAc = 3 / 1, twice); eluent: petroleum ether / EtOAc / DCM = 5 / 1 / 1; 1H NMR (500 MHz, CDCl3): δ 8.22 (d, J = 2.4 Hz, 1H),8.00 (d, J = 2.4 Hz, 1H), 7.90 (dd, J = 7.7, 1.4 Hz, 1H), 7.79–7.73 (m, 3H),7.64–7.61 (m, 1H), 7.56 (td, J = 7.5, 1.4 Hz, 1H), 7.52 (dd, J = 8.5, 2.4 Hz,1H), 7.46 (td, J = 7.6, 1.3 Hz, 1H), 7.44 (s, 1H), 7.36 (dd, J = 7.5, 1.3 Hz,1H), 7.34–7.26 (m, 3H), 7.24–7.19 (m, 3H), 7.15 (d, J = 2.2 Hz, 1H), 7.05 (d,J = 8.4 Hz, 1H), 6.97 (s, 1H), 6.88–6.80 (m, 3H), 5.19 (s, 2H), 4.43 (dd, J =8.2, 2.8 Hz, 1H), 4.40 (s, 2H), 4.21 (s, 1H), 3.86 (s, 2H), 2.70 (dt, J =12.7, 5.2 Hz, 1H), 2.54 (dt, J = 12.4, 5.8 Hz, 1H), 2.34 (s, 3H), 2.01 (dddd,J = 19.2, 9.7, 7.6, 4.4 Hz, 2H), 1.55 (p, J = 5.7 Hz, 2H); 13C NMR (126 MHz, CDCl3): δ 191.0, 170.8, 160.7, 144.9, 144.0, 143.6, 143.5, 140.6, 140.1, 139.7, 136.5, 135.7, 135.5, 135.3, 134.4, 132.9, 132.7, 130.7, 130.0, 129.6,129.4, 128.1, 127.9, 127.7, 127.2, 127.1, 125.3, 124.5, 124.3, 124.2, 123.3,122.4, 121.9, HRMS (ESI) m / z: [M + H] + calcd forC 55 H 42 N3O6S2, 868.2510; found, 868.2507.

[0055] I. Antibacterial Activity Test of Indole-4,5-Azazepine Compounds The following eight compounds (Examples 1, 9, 10, 13, 14, 15, 16 and 20) were selected from the above examples for antibacterial testing.

[0056] The testing steps are as follows: Four common agricultural pathogens—Cytospora sp. (apple rot), Fusarium graminearum (grass rot), Botrytis cinerea (tomato gray mold), and Sclerotium rolfsii (peanut white mold)—were selected. The antibacterial activity of the obtained compounds was determined using the mycelial growth rate method (Ann. Appl. Biol., 2008, 152, 369). All tested bacterial strains were provided by the Shandong Provincial Engineering Technology Research Center for Biological Pesticides.

[0057] First, weigh a certain amount of PDA (potato dextrose agar) into a wide-mouth flask, add distilled water to prepare the culture medium, and sterilize it in an autoclave at 120 °C for half an hour. Weigh 1 mg of the test drug and dissolve it in 10 mL of acetone to prepare a 100 mg / L solution. Then, take half of this solution and dilute it with dimethyl sulfoxide to 10 mL to prepare a 50 mg / L solution. Similarly, 25 mg / L and 12.5 mg / L solutions can be prepared. Take 5 mL of this solution and pour it into 50 mL of potato dextrose agar, mix well, and then pour the mixture into five separate autoclaved culture media. After cooling, inoculate each of the four pathogens using an inoculation loop, seal with sealing film, and transfer to a suitable temperature for incubation and observation. When the colony count in the control group (without any added agent) reached 80%, the colony count in the experimental group was measured using the cross-sectional method, and the antibacterial activity was calculated using the following formula: Inhibition rate = (Coronary diameter of control group - Colony diameter of experimental group) / Colony diameter of control group × 100%.

[0058] The experimental results are shown in Table 1 and Figures 1-4 As shown: Table 1. Antibacterial activity of each compound As shown in Table 1, compounds 1 to 8 all exhibit good inhibitory activity against apple rot fungus, grain rot fungus, tomato gray mold fungus, and peanut white mold fungus.

[0059] This invention provides antifungal effects of the above-mentioned compounds at concentrations of 12.5 mg / L, 25 mg / L, and 50 mg / L against *Fusarium oxysporum*, *Fusarium graminearum*, *Botrytis cinerea*, and *Alternaria alternata*, as shown in the figures below. Figures 1-4 As shown in the figure, compounds 1-4 exhibited excellent antibacterial activity at a low concentration of 25 mg / L against apple rot fungus, tomato gray mold fungus, and peanut white mold fungus. Especially against peanut white mold fungus, compounds 1-8 showed excellent antibacterial activity at a low concentration of 12.5 mg / L, with an inhibition rate as high as 100%. In contrast, inhibition of tomato gray mold fungus required relatively high drug concentrations.

[0060] In summary, in practical applications, the above-mentioned indole-4,5-nazazepine compounds can be used to prepare bactericidal drugs, or they can be used as lead compounds for bactericidal purposes after modification.

[0061] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. Use of an indole-4,5-nazetidine compound in the preparation of a medicine for preventing and treating plant pathogenic fungi. The structure of the indole-4,5-nazetidine compound is as follows: ； wherein R 1 one selected from p-toluenesulfonyl, p-chlorobenzenesulfonyl, p-methoxybenzenesulfonyl, 2-thiophenesulfonyl, 4-morpholinylsulfonyl;R 2 one selected from hydrogen, halogen, methyl;R 3 one selected from any available position on the phenyl ring, specifically selected from hydrogen, halogen, methyl, methoxy, methoxycarbonyl, and a drug molecule derivative;R 4 selected from hydrogen or methyl;R 5 one selected from hydrogen, methyl, phenyl; X is selected from one of S, O.

2. Use according to claim 1, characterized in that, The plant pathogenic fungi are selected from one or more of Valsa mali, Fusarium graminearum, Botrytis cinerea and Cercospora arachidicola.

3. Use according to claim 1, characterized in that, The indole-4,5-nazetidine compound is specifically selected from the following structural formula: 。 4. A pharmaceutical preparation for controlling plant disease fungi, characterized by, The pharmaceutical preparation contains the indole-4,5-nazetidine compound; The structure of the indole-4,5-nazetidine compound is as follows: ； wherein R 1 is selected from one of p-toluenesulfonyl, p-chlorobenzenesulfonyl, p-methoxybenzenesulfonyl, 2-thiophenesulfonyl, 4-morpholinosulfonyl; R 2 is selected from one of hydrogen, halogen, methyl; R 3 is selected from one of hydrogen, halogen, methyl, methoxy, methoxycarbonyl and a drug molecule derivative; R 4 is selected from one of hydrogen or methyl; R 5 is selected from one of hydrogen, methyl, phenyl; X is selected from one of S, O.

5. The pharmaceutical preparation for controlling plant disease fungi according to claim 4, characterized by, The pharmaceutical preparation further contains a pesticide-acceptable adjuvant, carrier, excipient or diluent.

6. The pharmaceutical preparation for controlling plant disease fungi according to claim 4, characterized by, The dosage form of the pharmaceutical preparation is selected from liquid agent, suspension agent, emulsion, wettable powder, tablet or granule.

7. The pharmaceutical preparation for controlling plant disease fungi according to claim 4, characterized by, The concentration of the indole-4,5-nazetidine compound in the pharmaceutical preparation is 10-200 mg / L.

8. The pharmaceutical preparation for controlling plant disease fungi according to claim 7, characterized by, The concentration of the indole-4,5-nazetidine compound in the pharmaceutical preparation is 12.5-100 mg / L.

9. A method for controlling plant disease fungi, characterized by, The method is to spray or root-irrigate the plant with the pharmaceutical preparation of any one of claims 4-8 to achieve the effect of preventing and treating plant pathogenic fungi.

10. The method of claim 9, wherein the method is for controlling a plant pathogenic fungus. The plant pathogenic fungi are selected from one or more of Valsa mali, Fusarium graminearum, Botrytis cinerea and Cercospora arachidicola.

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