Bacteriostatic application of indole azepine-spiro-benzothiophene ketone compound

Abstract

The invention discloses antibacterial application of an indole azepine-spiro-benzothiophene ketone compound, and belongs to the technical field of medicinal chemistry. The indole azepine-spiro-benzothiophene ketone compound provided by the invention has excellent inhibitory activity on four common pathogenic bacteria: peanut root rot bacteria, strawberry botrytis cinerea, valsa mali and cucumber fusarium wilt bacteria, so that the indole azepine-spiro-benzothiophene ketone compound has important application value in the field of agricultural germ control.

Description

Technical Field

[0001] The invention belongs to the technical field of medicinal chemistry, and specifically relates to the antibacterial use of indoleazepine-spiro-benzothiophene ketone compounds. Background Art

[0002] In agricultural production, various pathogens pose a serious threat to the health and yield of crops. For example, apple rot bacteria often cause apples to rot during storage and transportation, causing huge economic losses to fruit farmers; cucumber wilt bacteria can cause cucumber plants to wilt, turn yellow, and even die; strawberry gray mold can spread rapidly in a humid environment, causing strawberry fruits to rot, seriously affecting strawberry yield and quality; peanut root rot bacteria can damage the root system of peanuts, causing poor plant growth or even death. The above pathogens are generally highly contagious, spread quickly, and have strong adaptability to the environment, which poses a huge challenge to agricultural production.

[0003] Chemical control is a common method for the prevention and control of agricultural pathogenic fungi, but its long-term use will lead to drug resistance in pathogens, reduce the effectiveness of prevention and control, and may have adverse effects on the environment and non-target organisms, leading to ecological imbalance. With the emergence of drug-resistant strains, the spread of resistance has accelerated, and the prevention and control dilemma has intensified. Biological control has environmental advantages, but faces challenges in stability, efficacy and timing of application, and the effect takes a long time. Although disease-resistant varieties can effectively prevent and control certain diseases, not all crops have broad resistance, and may only be effective against specific pathogens. Although agricultural management measures can reduce the occurrence of pathogens, the effect is slow and is greatly affected by factors such as climate, making it difficult to achieve significant results in the short term.

[0004] In summary, although the current methods for the prevention and control of agricultural pathogenic fungi have achieved results to a certain extent, they still face many limitations. Among them, chemical control is the most commonly used method. Although it can quickly and effectively control diseases, its long-term use will cause pathogens to develop drug resistance, thereby reducing the prevention and control effect, and even making some traditional agents ineffective. Therefore, it is urgent to find new active molecules in the field of chemical control to deal with the problem of drug resistance. In-depth research on these new molecules can provide more accurate and sustainable solutions for agricultural disease control, make up for the shortcomings of existing prevention and control methods, and provide strong support for improving the health level of crops and the sustainability of agricultural production. Summary of the invention

[0005] The invention provides the use of indoleazepine-spiro-benzothiophenone compounds in preparing medicines with plant disease fungus inhibition activity.

[0006] In the present invention, the structural formula of the indole aza-spiro-benzothiophene ketone compound is as follows:

[0007]

[0008] Among them, R 1 Any one selected from trifluoromethanesulfonyl, cyclopropanesulfonyl, n-butanesulfonyl, 3-pyridinesulfonyl, 2-thiophenesulfonyl, 4-morpholinesulfonyl, acetyl and tert-butoxycarbonyl; R 2 At any available position of the benzene ring, specifically selected from halogen, methyl or methoxy; X is selected from S, O, N-Me, N-Bn.

[0009] The above-mentioned indole azapine-spiro-benzothiophene ketone compound is prepared by the following method:

[0010] An indole-derived aldehyde compound is mixed with a thiochromanone-derived compound, a solvent and a catalyst are added, the system temperature is controlled, and the reaction is stirred to obtain an indole aza-spiro-benzothiophene ketone compound.

[0011] In the above preparation method, the structural formula of the indole-derived aldehyde compound is as follows:

[0012]

[0013] Among them, R 1 Any one selected from the group consisting of trifluoromethanesulfonyl, cyclopropanesulfonyl, n-butanesulfonyl, 3-pyridinesulfonyl, 2-thiophenesulfonyl, 4-morpholinesulfonyl, acetyl and tert-butoxycarbonyl.

[0014] In the above preparation method, the structural formula of the thiochromanone-derived compound is selected from one of the following:

[0015]

[0016] Among them, R 2 At any available position of the benzene ring, specifically selected from halogen, methyl or methoxy; X is selected from S, O, N-Me, N-Bn.

[0017] In the above preparation method, the molar ratio of the indole-derived aldehyde compound to the thiochromanone-derived compound is selected from 1:1.2 to 1:1.5. In a specific embodiment, the molar ratio of the two is 1:1.2.

[0018] In the above preparation method, the solvent is ethanol.

[0019] In the above preparation method, the catalyst is selected from any one of benzoic acid, p-toluenesulfonic acid, methanesulfonic acid, and trifluoromethanesulfonic acid; in a specific embodiment, the catalyst is trifluoromethanesulfonic acid.

[0020] In the above preparation method, the amount of the catalyst used is 5 mol%.

[0021] In the above preparation method, the amount of the solvent is selected from: adding 10 to 20 L of solvent per mole of indole-derived aldehyde compound. In a specific embodiment, the amount of the solvent is: adding 10 L of solvent per mole of indole-derived aldehyde compound.

[0022] In the above preparation method, the reaction temperature is selected from 40 to 120° C. In a specific embodiment, the reaction temperature is 90° C.

[0023] The above reaction was carried out under sealed conditions.

[0024] In a specific embodiment, the indoleazepine-spiro-benzothiophenone compound can be specifically selected from the following structural formula:

[0025]

[0026]

[0027] In the present invention, the plant pathogenic fungi are selected from one or more of apple rot pathogen, cucumber wilt pathogen, strawberry gray mold pathogen and peanut root rot pathogen.

[0028] The beneficial effects of the present invention are:

[0029] The indoleazepine-spiro-benzothiophenone compounds provided by the present invention have excellent inhibitory activity against four common pathogens: peanut root rot pathogen, strawberry gray mold pathogen, apple rot pathogen and cucumber wilt pathogen, and thus have important application value in the field of agricultural pathogen control. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is the antibacterial chart of apple rot bacteria;

[0031] Figure 2 This is the antibacterial diagram of peanut root rot pathogen;

[0032] Figure 3 This is the antibacterial graph of strawberry gray mold;

[0033] Figure 4 This is the antibacterial chart of cucumber wilt bacteria. DETAILED DESCRIPTION

[0034] Other materials used in the present invention, if not otherwise stated, can be obtained through commercial channels. Other terms used in the present invention, unless otherwise specified, generally have the meanings commonly understood by those of ordinary skill in the art. The present invention is further described in detail below in conjunction with specific examples and with reference to data. The following examples are only for illustrating the present invention, and are not intended to limit the scope of the present invention in any way.

[0035] 1. Preparation of indole-aza-spiro-benzothiophene ketone compounds

[0036] The preparation of indole azepine-spiro-benzothiophene ketone compounds is as follows:

[0037] 0.2mmol of indole-derived aldehyde compounds and 0.24mmol of thiochromanone-derived compounds were placed in a sealed tube, 2mL of ethanol and 0.05mmol of trifluoromethanesulfonic acid (catalyst) were added, the system temperature was controlled at 90°C, stirring was continued, and the reaction was tracked by spotting on a thin layer chromatography plate until the raw materials reacted completely. After the reaction was completed, column chromatography was used for separation and purification, and the purified product was further rotary evaporated to obtain indole aza-spiro-benzothiophene ketone compounds.

[0038] The structural formula of the above-mentioned indole aza-spiro-benzothiophene ketone compound is as follows:

[0039]

[0040] Among them, R 1 Any one selected from trifluoromethanesulfonyl, cyclopropanesulfonyl, n-butanesulfonyl, 3-pyridinesulfonyl, 2-thiophenesulfonyl, 4-morpholinesulfonyl, acetyl and tert-butoxycarbonyl; R 2 At any available position of the benzene ring, specifically selected from halogen, methyl or methoxy; X is selected from S, O, N-Me, N-Bn.

[0041] The structural formula of the above-mentioned indole-derived aldehyde compound is as follows:

[0042]

[0043] Among them, R 1 Any one selected from the group consisting of trifluoromethanesulfonyl, cyclopropanesulfonyl, n-butanesulfonyl, 3-pyridinesulfonyl, 2-thiophenesulfonyl, 4-morpholinesulfonyl, acetyl and tert-butoxycarbonyl.

[0044] The structural formula of the above-mentioned thiochromanone-derived compound is selected from one of the following:

[0045]

[0046] Among them, R 2 At any available position of the benzene ring, specifically selected from halogen, methyl or methoxy; X is selected from S, O, N-Me, N-Bn.

[0047] According to the above method, the present invention prepared 31 indole aza-spiro-benzothiophene ketone compounds, and the specific preparation process thereof is referred to the following examples.

[0048] The chemical reaction formula is as follows:

[0049]

[0050] 0.2mmol 4-(pyrrolidin-1-yl)-1-toluenesulfonyl-1H-indole-3-carboxaldehyde and 0.24mmol benzo[b]thiophene-3(2H)-one were placed in a sealed tube, 2mL ethanol and 0.05mmol trifluoromethanesulfonic acid were added, the system temperature was controlled at 90°C, stirring was continued, and the reaction was tracked by spotting on a thin layer chromatography plate until the raw materials reacted completely. After the reaction was completed, column chromatography was used for separation and purification, and the purified product was further rotary evaporated to obtain the target product.

[0051] The NMR data of the 31 indoleazepine-spiro-benzothiophenone compounds are as follows:

[0052] Example 1

[0053]

[0054] 1'-tosyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]aze pino[4,3,2-cd]indol]-3-one: Yellow brown solid; 90.0mg, 90% yield, > 20:1dr; mp 226-228℃; Rf=0.40(petroleum ether / EtOAc=6 / 1); eluent:petroleum ether / EtOAc=8 / 1; 1 H NMR (400MHz, CDCl3): δ7.79(dd,J=7.9,1.3Hz,1H),7.77–7.73(m,2H),7.51(ddd,J=8.3,7.3,1.4Hz ,1H),7.40(d,J=8.2Hz,1H),7.32–7.26(m,2H),7.24-7.16(m,4H),6.39(d,J=8.1Hz,1H),4.10(dd,J =8.5,6.3Hz,1H),3.553.44(m,3H),3.13(d,J=16.3Hz,1H),2.33(s,3H),2.12(dtd,J=11.9,6.8,3. 9Hz,1H),1.97(dtt,J=11.5,7.4,4.2Hz,1H),1.85–1.73(m,1H),1.54(ddt,J=12.2,9.7,7.9Hz,1H); 1313C NMR(101MHz,CDCl3):δ202.4,153.5,144.8,141.3,136.9,136.2,135.2,130.6,129.9,127.4,127.0,126.150,124.9,124.3,121.0,118.6,116.8,106.4,102.7,71.7,68.0,50.8,38.0,31.1,22.6,21.6;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 28 H 25 N2O3S2,501.1301;found,501.1301.

[0055] Example 2

[0056]

[0057] 5-methyl-1'-tosyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one:Yellow solid;90.5mg,88%yield,>20:1dr;mp 150-152℃;Rf=0.36(petroleum ether / EtOAc=5 / 1);eluent:petroleum ether / EtOAc=5 / 1; 1 1H NMR(400MHz,CDCl3):δ7.79–7.71(m,2H),7.62–7.57(m,1H),7.39(d,J=8.2Hz,1H),7.35(dd,J=8.1,1.9Hz,1H),7.28(d,J=1.8Hz,1H),7.23–7.16(m,4H),6.38(d,J=8.1Hz,1H),4.10(dd,J=8.4,6.2Hz,1H),3.55–3.45(m,3H),3.15–3.08(m,1H),2.37(s,3H),2.34(s,3H),2.15–2.06(m,1H),2.02–1.93(m,1H),1.86–1.73(m,1H),1.59–1.48(m,1H); 1313C NMR(101MHz,CDCl3):δ202.5,150.5,144.8,141.4,137.6,137.0,135.3,135.0,130.8,129.9,127.3,127.0,126.2,124.0,121.0,118.8,116.8,106.3,102.7,72.0,68.0,50.8,38.1,31.1,22.6,21.7,20.9;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 29 H 27 N2O3S2,515.1458;found,515.1457.

[0058] Example 3

[0059]

[0060] 6-methyl-1'-tosyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Brown solid; 85.3 mg, 83% yield, >20:1 dr; mp 227 - 229 °C; Rf = 0.38 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1 1H NMR(400MHz,CDCl3):δ7.79–7.72(m,2H),7.68(d,J = 8.0Hz,1H),7.39(d,J = 8.2Hz,1H),7.28(d,J = 1.7Hz,1H),7.24–7.15(m,3H),7.09(s,1H),7.02(dd,J = 8.0,1.4Hz,1H),6.38(d,J = 8.1Hz,1H),4.09(dd,J = 8.5,6.3Hz,1H),3.55–3.45(m,3H),3.16–3.08(m,1H),2.38(s,3H),2.34(s,3H),2.16–2.07(m,1H),2.02–1.93(m,1H),1.86–1.73(m,1H),1.59–1.49(m,1H); 1313C NMR(101MHz,CDCl3):δ201.8,153.9,147.9,144.8,141.4,137.0,135.3,129.9,128.4,127.2,127.0,126.4,126.2,124.4,121.0,118.8,116.8,106.3,102.7,71.8,68.0,50.8,38.1,31.1,22.6,22.2,21.7;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 29 H 27 N2O3S2,515.1458;found,515.1458.

[0061] Example 4

[0062]

[0063] 5-chloro-1'-tosyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one:Yellow solid;95.2mg,89%yield,>20:1dr;mp 221-223℃;Rf=0.40(petroleum ether / EtOAc=5 / 1);eluent:petroleum ether / EtOAc=5 / 1; 1 1H NMR(500MHz,CDCl3):δ7.78–7.72(m,3H),7.46(dd,J=8.4,2.2Hz,1H),7.40(d,J=8.2Hz,1H),7.30(d,J=1.7Hz,1H),7.24–7.17(m,4H),6.39(d,J=8.1Hz,1H),4.10(dd,J=8.5,6.3Hz,1H),3.55–3.47(m,3H),3.14(dd,J=16.2,0.8Hz,1H),2.35(s,3H),2.12(dddd,J=12.1,7.3,6.3,4.0Hz,1H),2.03 1.95(m,1H),1.86–1.76(m,1H),1.53(ddt,J=12.2,9.7,7.9Hz,1H); 1313C NMR(126MHz,CDCl3):δ201.2,151.9,144.9,141.3,136.9,136.1,135.3,132.1,131.2,129.9,127.0,126.9,126.2,125.4,121.2,118.3,116.8,106.4,102.9,73.1,68.0,50.8,38.1,31.2,22.6,21.7;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 28 H 24 ClN2O3S2,535.0911;found,535.0910.

[0064] Example 5

[0065]

[0066] 5-bromo-1'-tosyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one:Yellow solid;102.0mg,88%yield,>20:1dr;mp 209-211℃;Rf=0.40(petroleum ether / EtOAc=5 / 1);eluent:petroleum ether / EtOAc=5 / 1; 1 1H NMR(400MHz,CDCl3):δ7.89(d,J=2.1Hz,1H),7.81–7.68(m,2H),7.59(dd,J=8.4,2.1Hz,1H),7.40(d,J=8.2Hz,1H),7.30(d,J=1.7Hz,1H),7.24–7.14(m,4H),6.39(d,J=8.1Hz,1H),4.09(dd,J=8.4,6.2Hz,1H),3.59–3.41(m,3H),3.18–3.09(m,1H),2.35(s,3H),2.16–2.07(m,1H),2.04–1.94(m,1H),1.87–1.75(m,1H),1.52(ddt,J=12.1,9.6,7.9Hz,1H); 1313C NMR(101MHz,CDCl3):δ201.1,152.5,144.9,141.3,138.8,136.9,135.3,132.4,130.0,129.9,127.0,126.2,125.7,121.2,118.5,118.3,116.8,106.4,102.9,72.9,68.0,50.9,38.0,31.2,22.6,21.7;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 28 H 24 BrN2O3S2,579.0406;found,579.0407.

[0067] Example 6

[0068]

[0069] 1'-tosyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzofuran-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2cd]indol]-3-one: Yellow solid;85.2mg, 88% yield, 4:1 dr;mp 134 - 136 °C;Rf = 0.40 (petroleum ether / EtOAc = 6 / 1);eluent: petroleum ether / EtOAc = 8 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.81–7.75(m,2H),7.72–7.68(m,1H),7.67 7.60(m,1H),7.43(d,J=8.3Hz,1H),7.25–7.21(m,3H),7.18(t,J=8.0Hz,1H),7.15–7.09(m,2H),6.47(d,J=8.0Hz,1H),4.04(dd,J=7.9,4.9Hz,1H),3.45(ddd,J=10.3,7.0,3.5Hz,1H),3.34–3.28(m,1H),3.26(dd,J=16.1,1.4Hz,1H),3.17(dd,J=16.2,1.3Hz,1H),2.35(s,3H),2.04–1.93(m,1H),1.92–1.77(m,2H),1.49 1.37(m,1H);for minor diastereomer:δ7.81–7.75(m,2H),7.72–7.68(m,1H),7.67–7.60(m,1H),7.45(d,J=8.3Hz,1H),7.25–7.21(m,3H),7.18(t,J=8.0Hz,1H),7.15–7.09(m,2H),6.51(d,J=7.9Hz,1H),4.01(dd,J=9.5,1.9Hz,1H),3.53(dd,J=15.8,2.0Hz,1H),3.40(t,J=7.6Hz,1H),3.11(ddd,J=10.8,6.9,4.1Hz,1H),2.90(d,J=15.8Hz,1H),2.35(s,3H),2.04–1.93(m,1H),1.92–1.77(m,2H),1.49–1.37(m,1H); 1313C NMR (126 MHz, CDCl3): for major diastereomer: δ 201.7, 172.4, 144.8, 143.9, 138.4, 136.6, 135.4, 129.9, 127.0, 126.0, 125.0, 122.3, 121.0, 120.4, 119.5, 117.0, 113.6, 106.1, 104.1, 92.2, 67.4, 49.9, 33.1, 28.9, 24.2, 21.7; for minor diastereomer: δ 201.5, 170.9, 146.1, 144.8, 138.3, 136.3, 135.5, 129.9, 127.0, 125.9, 124.4, 122.2, 121.8, 121.7, 120.6, 117.9, 113.6, 105.9, 105.3, 93.0, 69.7, 49.3, 34.2, 28.1, 24.2, 21.7; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 28 H 25 N2O4S, 485.1530; found, 485.1530.

[0070] Example 7

[0071]

[0072] 1'-((Trifluoromethyl)sulfonyl)-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow-brown solid; 86.1 mg, 90% yield, >20:1 dr; mp 178 - 180 °C; Rf = 0.40 (petroleum ether / EtOAc = 10 / 1); eluent: petroleum ether / EtOAc = 10 / 1; 11H NMR (400 MHz, CDCl3): δ 7.84–7.76 (m, 1H), 7.54 (ddd, J = 8.3, 7.2, 1.4 Hz, 1H), 7.37–7.27 (m, 3H), 7.25–7.20 (m, 1H), 7.07 (d, J = 2.0 Hz, 1H), 6.54 (dd, J = 7.9, 1.1 Hz, 1H), 4.18 (dd, J = 8.6, 6.2 Hz, 1H), 3.61–3.49 (m, 3H), 3.14 (dd, J = 16.3, 0.9 Hz, 1H), 2.22–2.12 (m, 1H), 2.04 (dddd, J = 11.8, 9.4, 6.8, 4.7 Hz, 1H), 1.93–1.81 (m, 1H), 1.59 (dddd, J = 12.1, 9.9, 8.5, 7.6 Hz, 1H); 13 13C NMR (101 MHz, CDCl3): δ 202.1, 153.2, 141.7, 137.6, 136.4, 130.5, 127.5, 127.4, 125.1, 124.4, 121.4, 120.6, 119.8 (q, J = 325.9 Hz), 116.6, 108.2, 102.8, 70.8, 68.1, 51.0, 37.8, 31.1, 22.7; 19 19F NMR (376 MHz, CDCl3) δ δ -74.87; HRMS (ESI-TOF) m / z: [M + H] + calcd for C22H18F3N2O3S2, 479.0705; found, 479.0705.

[0073] Example 8

[0074]

[0075] 1'-(cyclopropylsulfonyl)-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow solid; 70.3 mg, 78% yield, >20:1 dr; mp 167 - 169 °C; Rf = 0.20 (petroleum ether / EtOAc = 10 / 1); eluent: petroleum ether / EtOAc = 10 / 1; 1HNMR(500MHz,CDCl3):δ7.79(d,J=7.8Hz,1H),7.51(t,J=7.5Hz,1H),7.38(d,J=8.2Hz,1H),7.29(d,J=7.9Hz,1H),7.26–7.18(m,2H),7.10(s,1H),6.45(d,J=8.1Hz,1H),4.17(dd,J=8.5,6.2Hz,1H),3.61–3.49(m,3H),3.13(d,J=16.1Hz,1H),2.62(tt,J=8.4,4.7Hz,1H),2.20–2.12(m,1H),2.02(dtt,J=11.7,7.6,4.2Hz,1H),1.90–1.79(m,1H),1.58(dq,J=11.8,8.4Hz,1H),1.39–1.31(m,2H),1.04–0.92(m,2H); 13 C NMR(101MHz,CDCl3):δ202.3,153.5,141.5,137.2,136.2,130.6,127.4,126.1,124.9,124.3,121.3,117.8,116.8,106.2,102.5,71.8,68.0,50.9,38.0,31.14,31.09,22.6,6.07,6.03;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 24 H 23 N2O3S2,451.1145;found,451.1144.

[0076] Example 9

[0077]

[0078] 1'-(butylsulfonyl)-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow solid; 67.2mg, 72% yield, >20:1 dr; mp 161 - 163 °C; Rf = 0.28 (petroleum ether / EtOAc = 10 / 1); eluent: petroleum ether / EtOAc = 10 / 1; 11H NMR (500 MHz, CDCl3): δ 7.79 (dd, J = 7.8, 1.3 Hz, 1H), 7.58–7.48 (m, 1H), 7.35–7.28 (m, 2H), 7.28–7.19 (m, 2H), 7.15 (d, J = 1.8 Hz, 1H), 6.46 (d, J = 8.0 Hz, 1H), 4.19 (dd, J = 8.6, 6.2 Hz, 1H), 3.62–3.50 (m, 3H), 3.24 (t, J = 7.9 Hz, 2H), 3.14 (d, J = 16.2 Hz, 1H), 2.21–2.12 (m, 1H), 2.07–1.99 (m, 1H), 1.91–1.81 (m, 1H), 1.68–1.53 (m, 4H), 1.32 (h, J = 7.4 Hz, 2H), 0.85 (t, J = 7.4 Hz, 3H); 13 13C NMR (126 MHz, CDCl3): δ 202.3, 153.5, 141.6, 137.1, 136.2, 130.7, 127.4, 126.4, 125.0, 124.3, 121.5, 117.7, 116.7, 106.3, 102.1, 71.7, 68.1, 53.1, 50.9, 38.0, 31.2, 25.0, 22.6, 21.3, 13.5; HRMS (ESI-TOF) m / z: [M + H] + calcd for C 25 H 27 N2O3S2, 467.1458; found, 467.1458.

[0079] Example 10

[0080]

[0081] 1'-(pyridin-3-ylsulfonyl)-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'

[0082] pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow solid; 83.8 mg, 86% yield, >20:1 dr; mp 192 - 194 °C; Rf = 0.30 (petroleum ether / EtOAc = 3 / 1); eluent: petroleum ether / EtOAc = 3 / 1; 1HNMR(500MHz,CDCl3):δ9.07(d,J=2.3Hz,1H),8.74(dd,J=4.8,1.6Hz,1H),8.11(dt,J=8.2,1.9Hz,1H),7.78(dd,J=7.9,1.4Hz,1H),7.52(ddd,J=8.3,7.3,1.4Hz,1H),7.42–7.34(m,2H),7.30–7.19(m,4H),6.42(d,J=8.2Hz,1H),4.11(dd,J=8.6,6.3Hz,1H),3.55–3.41(m,3H),3.12(d,J=16.4Hz,1H),2.16–2.08(m,1H),2.03–1.94(m,1H),1.86–1.76(m,1H),1.58–1.50(m,1H); 13 C NMR(126MHz,CDCl3):δ202.2,154.2,153.4,147.7,141.6,137.0,136.2,134.8,134.5,130.6,127.4,126.8,125.0,124.3,123.8,120.6,120.2,116.8,107.1,102.5,71.3,68.0,50.9,38.0,31.1,22.6;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 26 H 22 N3O3S2,488.1097;found,488.1095.

[0083] Example 11

[0084]

[0085] 1'-(thiophen-2-ylsulfonyl)-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow solid; 85.7 mg, 87% yield, >20:1 dr; mp 249 - 251 °C; Rf = 0.33 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1HNMR(400MHz,CDCl3):δ7.82–7.75(m,1H),7.67(dd,J=3.8,1.4Hz,1H),7.56 7.49(m,2H),7.44(d,J=8.2Hz,1H),7.29(dd,J=7.9,0.9Hz,1H),7.26 7.19(m,3H),6.98(dd,J=5.0,3.8Hz,1H),6.43(d,J=8.1Hz,1H),4.12(dd,J=8.6,6.2Hz,1H),3.58–3.47(m,3H),3.13(dd,J=16.2,0.9Hz,1H),2.17 2.08(m,1H),2.04–1.95(m,1H),1.88–1.75(m,1H),1.60–1.50(m,1H); 13 CNMR(101MHz,CDCl3):δ202.4,153.5,141.5,138.1,136.9,136.2,133.4,133.1,130.6,127.5,127.4,126.4,125.0,124.3,120.8,119.7,116.9,106.9,102.9,71.5,68.0,50.9,38.0,31.1,22.6;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 25 H 21 N2O3S3,493.0709;found,493.0708.

[0086] Example 12

[0087]

[0088] 1'-(morpholinosulfonyl)-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one:Yellow solid; 84.2 mg, 85% yield, >20:1 dr; mp 135 - 137 °C; Rf = 0.22 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 11H NMR (500 MHz, CDCl3): δ 7.79 (dd, J = 7.8, 1.2 Hz, 1H), 7.55–7.49 (m, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.24–7.17 (m, 2H), 7.13 (d, J = 1.7 Hz, 1H), 6.43 (d, J = 8.1 Hz, 1H), 4.18 (dd, J = 8.6, 6.2 Hz, 1H), 3.64 3.59 (m, 4H), 3.59–3.50 (m, 3H), 3.24–3.17 (m, 4H), 3.14 (d, J = 16.1 Hz, 1H), 2.19–2.11 (m, 1H), 2.07–1.99 (m, 1H), 1.91–1.81 (m, 1H), 1.58 (ddt, J = 12.2, 9.9, 8.0 Hz, 1H); 13 13C NMR (126 MHz, CDCl3): δ 202.3, 153.5, 141.5, 137.4, 136.2, 130.7, 127.4, 126.0, 124.9, 124.3, 121.9, 117.0, 116.4, 105.9, 103.0, 71.8, 68.1, 65.9, 50.9, 46.8, 38.0, 31.1, 22.6; HRMS (ESI-TOF) m / z: [M + H] + calcd for C 25 H 26 N3O4S2, 496.1359; found, 496.1361.

[0089] Example 13

[0090]

[0091] 1'-acetyl-1',3',4a',5',6',7'-hexahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow solid; 50.5 mg, 65% yield, >20:1 dr; mp 221 - 223 °C; Rf = 0.35 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 11H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.2 Hz, 1H), 7.79 (dt, J = 7.8, 1.0 Hz, 1H), 7.52 (ddd, J = 8.4, 7.2, 1.4 Hz, 1H), 7.32–7.19 (m, 3H), 7.15–7.08 (m, 1H), 6.49 (d, J = 8.1 Hz, 1H), 4.15 (dd, J = 8.5, 6.3 Hz, 1H), 3.62–3.49 (m, 3H), 3.17 3.08 (m, 1H), 2.57 (s, 3H), 2.20–2.11 (m, 1H), 2.07–1.98 (m, 1H), 1.92–1.79 (m, 1H), 1.63–1.53 (m, 1H); 13 13C NMR (101 MHz, CDCl3): δ 202.5, 168.4, 153.5, 141.1, 137.8, 136.2, 130.7, 127.4, 126.9, 125.0, 124.4, 120.3, 118.8, 116.3, 107.4, 106.1, 71.7, 68.1, 50.9, 38.2, 31.2, 24.4, 22.7; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 23 H 21 N2O2S, 389.1318; found, 389.1318.

[0092] Example 14

[0093]

[0094] tert-butyl-3-oxo-4a',5',6',7'-tetrahydro-3H-spiro[benzo[b]thiophene-2,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indole]-1'(3'H)-carboxylate: Grey solid; 59.8 mg, 67% yield, >20:1 dr; mp 165 - 167 °C; Rf = 0.38 (petroleum ether / EtOAc = 10 / 1); eluent: petroleum ether / EtOAc = 10 / 1; 1HNMR(500MHz,CDCl3):δ7.79(dd,J=7.9,1.4Hz,1H),7.65(d,J=8.3Hz,1H),7.51(ddd,J=8.3,7.2,1.4Hz,1H),7.34–7.27(m,2H),7.25–7.18(m,2H),6.44(d,J=8.1Hz,1H),4.17(dd,J=8.4,6.3Hz,1H),3.62–3.54(m,2H),3.52(dd,J=16.1,2.1Hz,1H),3.16(d,J=16.1Hz,1H),2.20–2.13(m,1H),2.02(dtt,J=11.7,7.6,4.2Hz,1H),1.86(dddd,J=15.8,12.3,9.3,7.7Hz,1H),1.64–1.56(m,10H); 13 CNMR(126MHz,CDCl3):δ202.6,153.7,149.7,141.2,137.5,136.1,130.8,127.4,125.9,124.9,124.4,121.0,116.8,116.5,106.2,104.8,83.4,72.2,68.1,50.9,38.3,31.2,28.3,22.7;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 26 H 27 N2O3S,447.1737;found,447.1737.

[0095] Example 15

[0096]

[0097] 1,6-ditosyl-1,2,4,6-tetrahydro-3'H-spiro[azepino[4,3,2-cd]indole-3,2'-benzo[b]thiophen]-3'-one: Brown solid; 51.2 mg, 54% yield; mp 173 - 175 °C; Rf = 0.38 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 11H NMR (400 MHz, CDCl3): δ 7.84–7.72 (m, 3H), 7.59–7.53 (m, 1H), 7.45 (d, J = 8.3 Hz, 1H), 7.37 7.31 (m, 2H), 7.25–7.16 (m, 4H), 6.44 (d, J = 8.0 Hz, 1H), 3.83 (d, J = 14.3 Hz, 1H), 3.55 (dd, J = 16.0, 2.0 Hz, 1H), 3.44 (dd, J = 14.3, 1.6 Hz, 1H), 3.19 (d, J = 16.1 Hz, 1H), 3.06 (s, 3H), 2.35 (s, 3H); 13 13C NMR (101 MHz, CDCl3): δ 202.8, 152.4, 144.9, 136.8, 136.3, 135.3, 130.0, 127.5, 127.1, 125.8, 125.0, 124.4, 121.5, 119.5, 118.6, 106.3, 104.3, 69.5, 63.1, 42.3, 37.9, 21.7; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 26 H 23 N2O3S2, 475.1145; found, 475.1146.

[0098] Example 16

[0099]

[0100] 2'-chloro-4'-tosyl-4',6',7a',8',9',10'-hexahydro-3H-spiro[benzo[b]thiophene-2,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: Yellow solid; 95.0 mg, 89% yield, >20:1 dr; mp 262 - 264 °C; Rf = 0.20 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1HNMR(500MHz,CDCl3):δ7.78(dt,J=7.8,1.1Hz,1H),7.76–7.73(m,2H),7.53(ddd,J=8.2,7.2,1.4Hz,1H),7.41(d,J=1.6Hz,1H),7.31–7.28(m,1H),7.26–7.24(m,3H),7.22(ddd,J=7.9,7.2,0.9Hz,1H),6.36(d,J=1.7Hz,1H),4.11(dd,J=8.8,6.1Hz,1H),3.52–3.44(m,3H),3.09(dd,J=16.2,0.8Hz,1H),2.37(s,3H),2.15–2.09(m,1H),1.99(ddq,J=14.5,7.5,3.8Hz,1H),1.86–1.76(m,1H),1.54–1.51(m,1H); 13 C NMR(126MHz,CDCl3):δ202.1,153.4,145.2,141.6,137.1,136.3,135.2,132.2,130.6,130.1,127.5,127.1,125.1,124.4,121.4,118.5,115.4,106.9,102.8,71.1,68.1,51.0,37.9,31.1,22.6,21.8;HRMS(ESI-TOF)m / z:[M+H] + calcd for C 28 H 24 ClN2O3S2,535.0911;found,535.0914.

[0101] Example 17

[0102]

[0103] 2'-bromo-4'-tosyl-4',6',7a',8',9',10'-hexahydro-3H-spiro[benzo[b]thiophene-2,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-3-one: White solid; 100.8mg, 87% yield, >20:1 dr; mp 236 - 238 °C; Rf = 0.32 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1HNMR(500MHz,CDCl3):δ7.78(dd,J=7.8,1.3Hz,1H),7.76–7.72(m,2H),7.56(d,J=1.5Hz,1H),7.52(ddd,J=8.2,7.2,1.4Hz,1H),7.29(d,J=8.0Hz,1H),7.27–7.23(m,3H),7.23–7.19(m,1H),6.50(d,J=1.6Hz,1H),4.10(dd,J=8.8,6.2Hz,1H),3.52–3.43(m,3H),3.09(d,J=16.3Hz,1H),2.37(s,3H),2.15–2.08(m,1H),2.02–1.94(m,1H),1.80(ddq,J=12.4,10.4,8.2Hz,1H),1.53(dddd,J=12.2,10.2,8.8,7.6Hz,1H); 13 C NMR(126MHz,CDCl3):δ202.1,153.3,145.2,141.8,137.3,136.3,135.1,130.6,130.1,127.5,127.0,125.1,124.4,121.3,120.1,118.5,115.7,109.5,105.6,71.1,68.1,51.0,37.8,S15 31.1,22.6,21.7;HRMS(ESI-TOF)m / z:[M+H] + calcd forC 28 H 24 BrN2O3S2,579.0406;found,579.0406.

[0104] Example 18

[0105]

[0106] 1'-tosyl-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one:White solid;95.0mg,95% yield,>20:1 dr;mp 195-197℃;Rf = 0.40(petroleum ether / EtOAc = 5 / 1);eluent:petroleum ether / EtOAc = 5 / 1; 11H NMR (400 MHz, CDCl3): δ 7.79–7.69 (m, 2H), 7.47 (dd, J = 8.2, 0.7 Hz, 1H), 7.39 (dd, J = 7.7, 1.2 Hz, 1H), 7.30–7.19 (m, 5H), 6.93 (td, J = 7.6, 1.2 Hz, 1H), 6.80 (dd, J = 7.9, 1.3 Hz, 1H), 6.48 (d, J = 8.0 Hz, 1H), 4.08 (dd, J = 8.1, 4.5 Hz, 1H), 3.42–3.30 (m, 2H), 3.29–3.21 (m, 1H), 3.11 (dd, J = 16.1, 1.2 Hz, 1H), 2.36 (s, 3H), 2.12–1.99 (m, 1H), 1.73–1.60 (m, 2H), 1.38–1.26 (m, 1H); 13 13C NMR (101 MHz, CDCl3): δ 207.4, 144.8, 143.5, 137.8, 136.9, 135.3, 135.1, 129.9, 128.6, 127.5, 126.9, 126.2, 126.1, 122.7, 121.5, 119.6, 118.6, 106.6, 104.0, 69.7, 66.3, 50.6, 36.8, 30.4, 23.3, 21.7; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 28 H 25 N2O3S2, 501.1301; found, 501.1300.

[0107] Example 19

[0108]

[0109] 5-methyl-1'-tosyl-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: White solid; 94.7 mg, 92% yield, 7.7:1 dr; mp 208 - 211 °C; Rf = 0.40 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.76–7.70(m,2H),7.47(d,J=8.2Hz,1H),7.30–7.16(m,5H),7.11–7.06(m,1H),6.72(d,J=1.7Hz,1H),6.48(d,J=8.0Hz,1H),4.06(dd,J=8.4,4.3Hz,1H),3.37–3.23(m,3H),3.17–3.09(m,1H),2.33(s,3H),2.05–1.96(m,4H),1.76–1.55(m,2H),1.34(dddd,J=16.3,12.0,9.2,7.3Hz,1H);for minor diastereomer:δ7.79–7.76(m,2H),7.48(d,J=8.2Hz,1H),7.30–7.16(m,5H),7.14–7.11(m,1H),6.77(d,J=1.8Hz,1H),6.54(d,J=7.9Hz,1H),3.84(dd,J=9.8,2.2Hz,1H),3.62(dd,J=14.6,2.0Hz,1H),3.42(dd,J=8.6,6.8Hz,1H),3.17–3.09(m,1H),2.74(d,J=14.7Hz,1H),2.36(s,3H),2.25(s,3H),2.11–2.06(m,1H),1.82(dt,J=12.3,6.4Hz,1H),1.76–1.55(m,2H); 1313C NMR (126 MHz, CDCl3): for major diastereomer: δ 207.7, 144.7, 144.0, 138.2, 136.8, 135.9, 135.4, 131.6, 129.9, 129.4, 128.1, 126.9, 126.1, 122.4, 121.3, 120.0, 118.9, 106.4, 104.3, 70.1, 66.2, 50.5, 36.6, 30.0, 23.6, 21.7, 21.4; for minor diastereomer: δ 207.5, 146.9, 144.9, 141.5, 136.5, 135.5, 130.8, 130.0, 129.4, 126.9, 126.0, 125.5, 122.7, 122.0, 120.5, 119.7, 106.0, 105.6, 74.5, 65.5, 49.9, 35.2, 28.3, 24.3, 21.7, 21.5; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 29 H 27 N2O3S2, 515.1458; found, 515.1459.

[0110] Example 20

[0111]

[0112] 5-chloro-1'-tosyl-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: White solid; 101.7 mg, 95% yield, 3.8:1 dr; mp 219 - 221 °C; Rf = 0.38 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.74–7.68(m,2H),7.48(d,J=8.2Hz,1H),7.37–7.30(m,1H),7.28–7.16(m,5H),6.86(d,J=2.1Hz,1H),6.51(d,J=8.0Hz,1H),4.07(dd,J=8.4,4.4Hz,1H),3.39–3.27(m,3H),3.11(dd,J=16.0,1.3Hz,1H),2.34(s,3H),2.13–1.99(m,1H),1.78–1.68(m,1H),1.64–1.54(m,1H),1.36(dddd,J=16.4,12.2,9.2,7.4Hz,1H);for minor diastereomer:δ7.81–7.78(m,2H),7.49(d,J=8.2Hz,1H),7.37–7.30(m,2H),7.28–7.16(m,4H),6.92(d,J=2.1Hz,1H),6.55(d,J=7.8Hz,1H),3.78(dd,J=10.0,2.0Hz,1H),3.66(dd,J=14.6,2.0Hz,1H),3.43(dd,J=8.6,6.8Hz,1H),3.18–3.13(m,1H),2.74(d,J=14.6Hz,1H),2.36(s,3H),2.13–1.99(m,1H),1.88–1.81(m,1H),1.78–1.68(m,1H),1.64–1.54(m,1H); 1313C NMR (126 MHz, CDCl3): for major diastereomer: δ 206.2, 144.9, 143.6, 139.8, 136.9, 135.2, 133.5, 132.2, 129.9, 128.9, 127.6, 126.8, 126.3, 123.6, 121.7, 119.8, 118.1, 106.8, 104.5, 70.0, 66.6, 50.5, 36.6, 30.2, 23.5, 21.7; for minor diastereomer: δ 205.9, 146.7, 145.0, 143.1, 136.4, 135.3, 132.8, 132.6, 130.1, 128.8, 126.9, 126.1, 125.1, 124.0, 122.0, 120.9, 118.8, 106.2, 105.9, 74.5, 65.7, 49.8, 35.1, 28.3, 24.3, 21.7; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 28 H 24 ClN2O3S2, 535.0911; found, 535.0911.

[0113] Example 21

[0114]

[0115] 5-bromo-1'-tosyl-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: White solid; 108.9 mg, 94% yield, 2.8:1 dr; mp 158 - 160 °C; Rf = 0.38 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.73–7.69(m,2H),7.48(d,J=8.2,1H),7.42(dd,J=8.3,2.0Hz,1H),7.31–7.16(m,5H),7.05(d,J=2.1Hz,1H),6.52(d,J=8.0Hz,1H),4.07(dd,J=8.5,4.2Hz,1H),3.38 3.26(m,3H),3.18–3.09(m,1H),2.34(s,3H),2.12–1.98(m,1H),1.78–1.68(m,1H),1.64–1.52(m,1H),1.36(dtt,J=12.2,9.2,7.4Hz,1H);for minor diastereomer:δ7.83 7.78(m,2H),7.49(d,J=8.2,1H),7.46(dd,J=8.3,2.0Hz,1H),7.31–7.16(m,5H),7.08(d,J=2.0Hz,1H),6.55(d,J=7.8Hz,1H),3.79(dd,J=9.9,2.0Hz,1H),3.65(dd,J=14.7,2.0Hz,1H),3.43(dd,J=8.7,6.8Hz,1H),3.18–3.09(m,1H),2.74(d,J=14.6Hz,1H),2.36(s,3H),2.12–1.98(m,1H),1.88–1.81(m,1H),1.78–1.68(m,1H),1.64–1.52(m,1H); 1313C NMR(126MHz,CDCl3): for both major and minor diastereomers: δ 206.0, 205.7, 146.7, 144.9, 144.8, 143.8, 143.4, 140.3, 136.9, 136.4, 135.4, 135.3, 134.2, 133.5, 131.72, 131.66, 130.5, 130.2, 130.0, 127.9, 126.9, 126.8, 126.2, 126.1, 124.4, 123.9, 122.0, 121.6, 120.8, 120.3, 119.92, 119.87, 118.6, 118.1, 106.7, 106.2, 105.8, 104.6, 74.5, 70.2, 66.5, 65.6, 50.5, 49.8, 36.5, 35.1, 30.0, 28.3, 24.3, 23.6, 21.8, 21.7; HRMS(ESI-TOF) m / z: [M+H] + calcd for C 28 H 24 BrN2O3S2, 579.0406; found, 579.0406.

[0116] Example 22

[0117]

[0118] 1'-tosyl-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzofuran-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2cd]indol]-2-one: White solid; 71.7 mg, 74% yield, >20:1 dr; mp 204 - 206 °C; Rf = 0.33 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 11H NMR (400 MHz, CDCl3): δ 7.77–7.68 (m, 2H), 7.46 (d, J = 8.3 Hz, 1H), 7.30–7.17 (m, 5H), 7.13 (dd, J = 8.1, 1.1 Hz, 1H), 6.79 (td, J = 7.6, 1.1 Hz, 1H), 6.49–6.40 (m, 2H), 4.11 (t, J = 6.7 Hz, 1H), 3.51–3.41 (m, 2H), 3.26 (ddd, J = 9.2, 7.4, 5.5 Hz, 1H), 3.10 (dd, J = 16.0, 0.9 Hz, 1H), 2.35 (s, 3H), 2.25–2.16 (m, 1H), 1.77 1.66 (m, 1H), 1.52–1.33 (m, 2H); 13 13C NMR (101 MHz, CDCl3): δ 177.8, 153.3, 144.9, 142.2, 137.0, 135.1, 129.9, 129.2, 126.95, 126.92, 126.8, 126.3, 124.3, 121.9, 118.3, 117.5, 110.4, 106.7, 103.3, 67.4, 55.2, 51.0, 36.1, 31.7, 22.6, 21.7; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 28 H 25 N2O4S, 485.1530; found, 485.1529.

[0119] Example 23

[0120]

[0121] 1-methyl-1'-tosyl-1',3',4a',5',6',7'-hexahydrospiro[indoline-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2cd]indol]-2-one: Yellow solid; 73.6 mg, 74% yield, 16:1 dr; mp 224 - 226 °C; Rf = 0.20 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 11H NMR (500 MHz, CDCl3): δ 7.73–7.68 (m, 2H), 7.44 (d, J = 8.1 Hz, 1H), 7.25–7.18 (m, 5H), 6.87 (d, J = 7.7 Hz, 1H), 6.69 (td, J = 7.5, 1.0 Hz, 1H), 6.45 (dd, J = 7.7, 1.2 Hz, 1H), 6.42 (d, J = 8.0 Hz, 1H), 4.09 (t, J = 7.0 Hz, 1H), 3.48–3.41 (m, 2H), 3.30–3.24 (m, 4H), 2.89 (dd, J = 16.2, 0.9 Hz, 1H), 2.35 (s, 3H), 2.13–2.04 (m, 1H), 1.73 1.64 (m, 1H), 1.42 (dddd, J = 13.1, 11.7, 7.4, 5.7 Hz, 1H), 1.28–1.20 (m, 1H); 13 13C NMR (126 MHz, CDCl3): δ 178.3, 144.7, 144.0, 142.6, 137.1, 135.3, 129.8, 128.6, 128.3, 126.9, 126.5, 126.1, 122.7, 121.4, 119.1, 118.4, 107.8, 106.5, 102.9, 67.3, 55.6, 51.0, 35.5, 31.0, 26.2, 22.6, 21.7; HRMS (ESI TOF) m / z: [M+H] + calcd for C 29 H 28 N3O3S, 498.1846; found, 498.1846.

[0122] Example 24

[0123]

[0124] 1,5-dimethyl-4'-tosyl-4',6',7a',8',9',10'-hexahydrospiro[indoline-3,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 61.4 mg, 60% yield, 2.4:1 dr; mp 121 - 123 °C; Rf = 0.20 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.72(d,J=7.8Hz,2H),7.45(d,J=8.2Hz,1H),7.25–7.15(m,4H),7.03(d,J=7.9Hz,1H),6.786.73(m,1H),6.42(d,J=8.0Hz,1H),6.28(s,1H),4.07(t,J=6.9Hz,1H),3.46–3.39(m,2H),3.30–3.22(m,4H),2.88(d,J=16.2Hz,1H),2.33(s,3H),2.06(dq,J=13.3,6.8Hz,1H),1.96(s,3H),1.72–1.63(m,1H),1.42(dp,J=13.3,6.8Hz,1H),1.23(dt,J=14.4,7.1Hz,1H);for minor diastereomer:δ7.77(d,J=7.8Hz,2H),7.48(d,J=8.3Hz,1H),7.25–7.15(m,4H),7.09(d,J=7.9Hz,1H),6.78–6.73(m,1H),6.72(s,1H),6.54(d,J=7.8Hz,1H),3.84(d,J=9.8Hz,1H),3.67(dt,J=14.4,1.7Hz,1H),3.46–3.39(m,1H),3.25(s,3H),3.10(ddd,J=14.6,8.9,5.4Hz,1H),2.55(d,J=14.5Hz,1H),2.36(s,3H),2.27(s,3H),2.21(td,J=11.7,6.1Hz,1H),1.76(dt,J=12.2,6.2Hz,1H),1.72–1.63(m,1H),1.15(dd,J=13.0,7.0Hz,1H); 1313C NMR(126MHz,CDCl3): for both major and minor diastereomers: δ 178.3, 178.1, 147.5, 144.8, 144.6, 142.8, 141.6, 140.5, 137.1, 136.5, 135.5, 135.3, 133.5, 132.2, 132.0, 129.9, 129.8, 128.9, 128.55, 128.52, 127.1, 126.9, 126.1, 125.9, 123.9, 122.5, 121.3, 120.5, 120.2, 119.2, 118.5, 107.8, 107.5, 106.4, 105.9, 105.5, 102.9, 72.0, 67.3, 55.7, 55.6, 50.9, 49.8, 35.4, 33.3, 30.9, 28.7, 26.4, 26.3, 24.2, 22.7, 21.70, 21.66, 21.3, 21.2; HRMS(ESI-TOF) m / z: [M+H] + calcd for C 30 H 30 N3O3S, 512.2002; found, 512.2001.

[0125] Example 25

[0126]

[0127] 4-chloro-1-methyl-4'-tosyl-4',6',7a',8',9',10'-hexahydrospiro[indoline-3,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 80.9 mg, 76% yield, 1.2:1 dr; mp 146 - 148 °C; Rf = 0.20 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for majordiastereomer:δ7.74–7.69(m,2H),7.41(d,J=8.3Hz,1H),7.27–7.12(m,5H),6.97(dd,J=8.2,0.9Hz,1H),6.76(dd,J=7.8,0.9Hz,1H),6.46(d,J=7.9Hz,1H),4.60(dd,J=8.7,3.5Hz,1H),3.47–3.42(m,1H),3.41–3.36(m,1H),3.35–3.25(m,2H),3.21(s,3H),2.33(s,3H),1.94 1.86(m,1H),1.83–1.67(m,2H),1.18(ddd,J=13.3,7.0,3.4Hz,1H);for minordiastereomer:δ7.80–7.76(m,2H),7.40(d,J=8.3Hz,1H),7.27–7.12(m,5H),7.04(dd,J=8.2,0.9Hz,1H),6.80(dd,J=7.9,0.9Hz,1H),6.46(d,J=7.9Hz,1H),4.25(dd,J=9.2,1.8Hz,1H),3.92(dd,J=15.6,2.1Hz,1H),3.41–3.36(m,1H),3.22(s,3H),3.13(ddd,J=10.5,8.6,6.1Hz,1H),2.78(d,J=15.6Hz,1H),2.32(s,3H),1.83–1.67(m,3H),1.01(dt,J=10.4,3.9Hz,1H); 13CNMR(126MHz,CDCl3): for both major and minor diastereomers: δ 178.0, 176.6, 146.3, 146.0, 145.2, 144.6, 144.5, 136.6, 136.5, 135.7, 135.6, 132.4, 130.5, 130.1, 129.9, 129.8, 129.6, 127.8, 126.93, 126.86, 125.7, 125.6, 124.7, 124.1, 121.7, 122.0, 121.0, 120.4, 120.3, 119.8, 106.7, 105.9, 105.0, 104.9, 104.4, 70.8, 66.8, 57.8, 56.7, 50.3, 48.9, 32.5, 29.7, 29.3, 28.2, 26.6, 26.5, 24.8, 23.7, 21.6; HRMS(ESI-TOF) m / z: [M+H] + calcd for C 29 H 27 ClN3O3S, 532.1456; found, 532.1456.

[0128] Example 26

[0129]

[0130] 5-chloro-1-methyl-4'-tosyl-4',6',7a',8',9',10'-hexahydrospiro[indoline-3,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 86.2 mg, 81% yield, 4:1 dr; mp 205 - 208 °C; Rf = 0.21 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.66(d,J=7.8Hz,2H),7.44(d,J=8.3Hz,1H),7.29–7.14(m,5H),6.83–6.76(m,1H),6.44(d,J=8.1Hz,1H),6.39(t,J=1.7Hz,1H),4.06(t,J=7.0Hz,1H),3.47–3.39(m,2H),3.31(dt,J=8.7,6.5Hz,1H),3.24(s,4H),2.88(d,J=16.2Hz,1H),2.32(s,3H),2.07(dq,J=13.4,6.8Hz,1H),1.73–1.63(m,1H),1.42(dp,J=13.5,6.9Hz,1H),1.25–1.18(m,1H);forminor diastereomer:δ7.77(d,J=7.8Hz,2H),7.48(d,J=8.3Hz,1H),7.29–7.14(m,5H),6.83 6.76(m,2H),6.53(d,J=7.8Hz,1H),3.76(dd,J=9.8,2.1Hz,1H),3.68(dt,J=14.4,1.7Hz,1H),3.47–3.39(m,1H),3.26(s,3H),3.09(td,J=9.6,8.7,5.6Hz,1H),2.54(d,J=14.5Hz,1H),2.35(s,3H),2.21(dq,J=17.7,5.3Hz,1H),1.77(dt,J=12.1,6.3Hz,1H),1.73–1.63(m,1H),1.12(dd,J=13.4,6.9Hz,1H); 1313C NMR(126MHz,CDCl3): for major diastereomer: δ 177.8, 144.8, 142.6, 142.4, 137.1, 135.1, 130.0, 129.8, 128.3, 127.9, 126.65, 126.62, 126.3, 121.6, 118.5, 118.2, 108.7, 106.7, 103.2, 67.2, 56.0, 50.9, 35.3, 31.0, 26.3, 22.6, 21.7; for minor diastereomer: δ 177.6, 147.2, 144.8, 141.4, 136.4, 135.3, 135.0, 130.5, 128.2, 128.0, 126.8, 126.0, 123.5, 122.4, 120.5, 119.8, 109.0, 106.1, 105.8, 71.8, 55.9, 49.6, 33.1, 28.7, 26.4, 24.2, 21.7; HRMS(ESI-TOF) m / z: [M+H] + calcd for C 29 H 27 ClN3O3S, 532.1456; found, 532.1456.

[0131] Example 27

[0132]

[0133] 4-bromo-1-methyl-4'-tosyl-4',6',7a',8',9',10'-hexahydrospiro[indoline-3,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 92.2 mg, 80% yield, 1.5:1 dr; mp 149 - 152 °C; Rf = 0.24 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.73(d,J=7.8Hz,2H),7.43(d,J=8.3Hz,1H),7.28–7.11(m,6H),6.80(dd,J=7.0,1.6Hz,1H),6.46(d,J=8.0Hz,1H),4.68(dd,J=8.2,3.8Hz,1H),3.51–3.43(m,2H),3.36–3.28(m,2H),3.19(s,3H),2.33(s,3H),1.90–1.65(m,3H),1.22–1.16(m,1H);for minordiastereomer:δ7.79(d,J=7.8Hz,2H),7.42(d,J=8.3Hz,1H),7.28–7.11(m,6H),6.84(d,J=7.7Hz,1H),6.45(d,J=8.0Hz,1H),4.26(d,J=8.4Hz,1H),4.04(dt,J=15.6,1.7Hz,1H),3.36–3.28(m,1H),3.22(s,3H),3.14–3.07(m,1H),2.77(d,J=15.6Hz,1H),2.33(s,3H),1.90–1.65(m,3H),1.04 0.96(m,1H); 13 C NMR(126MHz,CDCl3):for both major andminor diastereomers:δ178.1,176.4,146.21,146.18,145.5,144.9,144.62,144.57,136.6,136.5,135.75,135.72,132.0,129.9,129.79,129.76,129.5,128.0,127.3,127.0,126.9,125.7,125.5,121.6,121.0,120.7,120.6,120.5,120.3,119.8,118.7,107.25,107.22,105.9,104.93,104.90,104.2,70.9,66.6,57.8,56.7,50.4,49.0,32.4,29.9,29.1,28.0,26.50,26.49,24.9,23.70,21.67,21.6;HRMS(ESI-TOF)m / z:[M+H] + calcd forC 29 H 27BrN3O3S, 576.0951; found, 576.0951.

[0134] Example 28

[0135]

[0136] 5-bromo-1-methyl-4'-tosyl-4',6',7a',8',9',10'-hexahydrospiro[indoline-3,7'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 99.2 mg, 86% yield, 10:1 dr; mp 214 - 217 °C; Rf = 0.20 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1H NMR(500MHz,CDCl3):for major diastereomer:δ7.67(d,J=7.9Hz,2H),7.45(d,J=8.3Hz,1H),7.35(dt,J=8.4,1.6Hz,1H),7.29–7.14(m,4H),6.78–6.71(m,1H),6.56(t,J=1.7Hz,1H),6.44(d,J=8.0Hz,1H),4.05(t,J=6.9Hz,1H),3.46–3.38(m,2H),3.31(dt,J=8.7,6.4Hz,1H),3.24(s,3H),2.89(d,J=16.2Hz,1H),2.32(s,3H),2.10–2.03(m,1H),1.75–1.64(m,1H),1.42(dp,J=13.5,6.9Hz,1H),1.21(dt,J=14.1,7.1Hz,1H);for minor diastereomer:δ7.78(d,J=7.9Hz,2H),7.48(d,J=8.2Hz,1H),7.41(dt,J=8.2,1.6Hz,1H),7.29–7.14(m,4H),6.97(t,J=1.7Hz,1H),6.78 6.71(m,1H),6.53(d,J=7.8Hz,1H),3.77(d,J=9.7Hz,1H),3.70–3.65(m,1H),3.46–3.38(m,1H),3.25(s,3H),3.12–3.07(m,1H),2.55(d,J=14.5Hz,1H),2.35(s,3H),2.20(td,J=11.8,10.7,5.5Hz,1H),1.80–1.75(m,1H),1.75–1.64(m,1H),1.15–1.09(m,1H); 1313C NMR(126MHz,CDCl3): for major diastereomer: δ177.7, 144.7, 143.0, 142.4, 137.1, 135.2, 131.2, 130.9, 129.9, 129.4, 126.7, 126.3, 121.6, 118.5, 118.3, 115.4, 109.3, 106.7, 103.3, 67.2, 56.0, 50.9, 35.3, 31.0, 26.3, 22.7, 21.7; for minor diastereomer: δ177.5, 147.2, 144.8, 141.9, 136.4, 135.4, 135.3, 131.1, 130.1, 126.8, 126.2, 126.0, 122.4, 120.5, 119.6, 109.6, 106.1, 105.8, 71.8, 55.9, 49.6, 34.2, 33.2, 26.4, 24.2, 22.4; HRMS(ESI-TOF) m / z: [[M+H]] + calcd for C 29 H 27 BrN3O3S, 576.0951; found, 576.0951.

[0137] Example 29

[0138]

[0139] 1'-(cyclopropylsulfonyl)-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Light yellow solid; 84.7 mg, 94% yield, 4.3:1 dr; mp 112 - 114 °C; Rf = 0.40 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1HNMR(500MHz,CDCl3):for majordiastereomer:δ7.38–7.29(m,2H),7.21 7.15(m,2H),6.96(t,J=1.4Hz,1H),6.96–6.91(m,1H),6.89(dd,J=7.9,1.5Hz,1H),6.46(d,J=7.9Hz,1H),4.08(dd,J=8.2,4.4Hz,1H),3.34(td,J=8.8,6.8Hz,1H),3.30–3.20(m,2H),3.05(dd,J=16.0,1.2Hz,1H),2.55(tt,J=8.0,4.8Hz,1H),2.09–1.95(m,1H),1.74–1.54(m,2H),1.38–1.19(m,3H),0.99–0.74(m,2H);for minor diastereomer:δ7.38–7.29(m,2H),7.23(td,J=7.6,1.3Hz,1H),7.14–7.09(m,2H),6.99(dd,J=7.8,1.3Hz,1H),6.96–6.91(m,1H),6.52(d,J=7.8Hz,1H),3.88(dd,J=9.8,2.2Hz,1H),3.62(dd,J=14.6,2.0Hz,1H),3.42–3.37(m,1H),3.16–3.09(m,1H),2.70(d,J=14.6Hz,1H),2.55(tt,J=8.0,4.8Hz,1H),2.09–1.95(m,1H),1.82–1.74(m,1H),1.74–1.54(m,2H),S20 1.38–1.19(m,2H),0.99–0.74(m,2H); 1313C NMR (126 MHz, CDCl3): for major diastereomer: δ 207.3, 143.8, 138.0, 137.0, 135.0, 128.6, 127.4, 126.2, 126.0, 122.7, 121.6, 119.7, 117.6, 106.4, 103.8, 69.8, 66.3, 50.6, 36.7, 31.2, 30.3, 23.4, 6.1, 6.0; for minor diastereomer: δ 206.9, 146.9, 141.5, 136.7, 134.3, 128.5, 126.7, 126.0, 124.8, 123.0, 121.8, 120.8, 118.5, 105.9, 105.2, 74.5, 65.5, 49.9, 35.2, 31.2, 28.4, 24.3, 6.1, 6.0; HRMS (ESI-TOF) m / z: [M+H] + calcd for C 24 H 23 N2O3S2, 451.1145; found, 451.1146.

[0140] Example 30

[0141]

[0142] 1'-(Thiophen-2-ylsulfonyl)-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 93.5 mg, 95% yield, >20:1 dr; mp 226 - 228 °C; Rf = 0.40 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 11H NMR (400 MHz, CDCl3): δ 7.66 (dd, J = 3.8, 1.4 Hz, 1H), 7.59–7.45 (m, 2H), 7.39 (d, J = 7.8 Hz, 1H), 7.32–7.24 (m, 2H), 7.18 (s, 1H), 6.99 (dd, J = 5.0, 3.8 Hz, 1H), 6.94 (td, J = 7.7, 1.3 Hz, 1H), 6.86–6.75 (m, 1H), 6.53 (d, J = 8.0 Hz, 1H), 4.09 (dd, J = 8.0, 4.5 Hz, 1H), 3.45–3.22 (m, 3H), 3.11 (d, J = 15.8 Hz, 1H), 2.07 (ddt, J = 15.6, 12.4, 8.4 Hz, 1H), 1.74–1.60 (m, 2H), 1.40–1.28 (m, 1H); 13 13C NMR (101 MHz, CDCl3): δ 207.3, 143.6, 138.0, 137.8, 136.9, 135.1, 133.4, 133.1, 128.6, 127.5, 127.4, 126.33, 126.28, 122.7, 121.2, 119.7, 119.6, 107.1, 104.2, 69.7, 66.2, 50.6, 36.7, 30.4, 23.3; HRMS (ESI-TOF) m / z: [M + H] + calcd for C 25 H 21 N2O3S3, 493.0709; found, 493.0709.

[0143] Example 31

[0144]

[0145] 1'-(Pyridin-3-ylsulfonyl)-1',3',4a',5',6',7'-hexahydro-2H-spiro[benzo[b]thiophene-3,4'-pyrrolo[1',2':1,7]azepino[4,3,2-cd]indol]-2-one: Yellow solid; 85.8 mg, 88% yield, >20:1 dr; mp 195 - 197 °C; Rf = 0.28 (petroleum ether / EtOAc = 5 / 1); eluent: petroleum ether / EtOAc = 5 / 1; 1HNMR (500MHz, CDCl3): δ9.07(dd,J=2.4,0.8Hz,1H),8.75(dd,J=4.9,1.6Hz,1H),8.09(ddd,J=8.1,2.4,1.6Hz,1H),7.48(d,J=8 .1Hz,1H),7.41–7.35(m,2H),7.29–7.23(m,2H),7.20(t,J=1.5Hz,1H),6.94(td,J=7.7,1.2Hz,1H),6.79(dd,J=7.8,1.3Hz,1H) ,6.52(d,J=8.0Hz,1H),4.06(dd,J=8.2,4.6Hz,1H),3.37(td,J=8.8,7.1Hz,1H),3.31(dd,J=16.1,1.7Hz,1H),3.26(ddd,J=9.1 ,7.3,3.6Hz,1H),3.11(dd,J=16.1,1.2Hz,1H),2.09–2.01(m,1H),1.72–1.58(m,2H),1.33(dddd,J=15.7,11.4,8.7,7.2Hz,1H); 13 C NMR (101MHz, CDCl3): δ207.2,154.3,147.6,143.8,137.7,136.8,135.1,134.7,134.4,128.7,127.3,126.7,126. 3,123.8,122.8,120.9,120.2,119.8,107.3,103.9,69.8,66.1,50.6,36.6,30.3,23.3; HRMS(ESI-TOF)m / z:[M+H] + Calculate for C 26 H 22 N3O3S2,488.1097; found,488.1099.

[0146] 2. Antibacterial activity test of indoleazepine-spiro-benzothiophenone compounds

[0147] The following four compounds (Example 1, Example 6, Example 18 and Example 22) were selected from the above examples for antibacterial testing.

[0148]

[0149] The test steps are as follows:

[0150] Four common agricultural pathogens, apple rot, cucumber wilt, strawberry gray mold and peanut root rot, were selected and the antibacterial activity of the obtained compounds was determined by the mycelium growth rate method (Ann. Appl. Biol., 2008, 152, 369). The above test strains were provided by Shandong Biopesticide Engineering Technology Research Center.

[0151] First, weigh a certain amount of PDA (potato dextrose agar) in a wide-mouth flask, add distilled water to make a culture medium and sterilize it in a 120℃ autoclave for half an hour. Weigh 1mg of the drug to be tested and dissolve it in 10mL of acetone to make a 100mg / L agent. Then take half of the agent and dilute it to 10mL with acetone to make a 50mg / L agent. By analogy, you can make 25mg / L and 12.5mg / L agents. Take 5mL of the agent and pour it into 50mL of potato dextrose agar to mix well, and then pour it into 5 high-temperature sterilized culture media respectively. After cooling, use an inoculation loop to inoculate the above four pathogens respectively, seal it with a sealing film, and transfer it to a suitable temperature for cultivation and observation. When the colony in the culture dish of the control group without the addition of the agent reaches 80%, the colony of the experimental group is measured by the cross method, and the antibacterial activity is calculated. The formula is as follows:

[0152] Inhibition rate = (colony diameter of control group - colony diameter of experimental group) / colony diameter of control group × 100%;

[0153] The test results are shown in Table 1:

[0154] Table 1 Antibacterial activity of each compound

[0155]

[0156] As shown in Table 1, compounds 1 to 4 have good inhibitory activity against apple rot pathogen, peanut root rot pathogen, strawberry gray mold pathogen and cucumber wilt pathogen.

[0157] The present invention provides the antibacterial effect diagrams of the above compounds at concentrations of 12.5 mg / L, 25 mg / L, and 50 mg / L on apple rot pathogen, peanut root rot pathogen, strawberry gray mold pathogen, and cucumber wilt pathogen, respectively. Figure 1 to Figure 4 As shown. Among them: for apple rot fungus, cucumber wilt fungus and strawberry gray mold fungus, compounds 1-4 can show very excellent antibacterial activity at a low concentration of 25 mg / L; especially for strawberry gray mold fungus, compounds 1-4 show excellent antibacterial activity at a low concentration of 12.5 mg / L, and the antibacterial rate is as high as 100%. Relatively speaking, a relatively high drug concentration is required for the inhibition of peanut root rot fungus.

[0158] In summary, in practical applications, the above-mentioned indole azapine-spiro-benzothiophene ketone compounds can be used to prepare bactericidal drugs, and can also be used as lead compounds and used for bactericidal purposes after modification.

[0159] The above is only a preferred embodiment of the present invention, and does not limit the present invention in other forms. Any technician familiar with the profession may use the above disclosed technical content to change or modify it into an equivalent embodiment with equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiment according to the technical essence of the present invention without departing from the technical solution of the present invention still belongs to the protection scope of the technical solution of the present invention.

Claims

1. Application of indoleazepine-spiro-benzothiophenone compounds in the preparation of drugs with plant disease fungal inhibitory activity.

2. The use according to claim 1, characterized in that: The structural formula of the indoleazepine-spiro-benzothiophene ketone compound is as follows: Among them, R 1 Any one selected from trifluoromethanesulfonyl, cyclopropanesulfonyl, n-butanesulfonyl, 3-pyridinesulfonyl, 2-thiophenesulfonyl, 4-morpholinesulfonyl, acetyl and tert-butoxycarbonyl; R 2 At any available position of the benzene ring, specifically selected from halogen, methyl or methoxy; X is selected from S, O, N-Me, N-Bn.

3. The use according to claim 1, characterized in that: The indole azepine-spiro-benzothiophene ketone compound is prepared by the following method: An indole-derived aldehyde compound is mixed with a thiochromanone-derived compound, a solvent and a catalyst are added, the system temperature is controlled, and the reaction is stirred to obtain an indole aza-spiro-benzothiophene ketone compound.

4. The use according to claim 3, characterized in that: The structural formula of the indole-derived aldehyde compound is as follows: Among them, R 1 Any one selected from trifluoromethanesulfonyl, cyclopropanesulfonyl, n-butanesulfonyl, 3-pyridinesulfonyl, 2-thiophenesulfonyl, 4-morpholinesulfonyl, acetyl and tert-butoxycarbonyl; The structural formula of the thiochromanone-derived compound is selected from one of the following: Among them, R 2 At any available position of the benzene ring, specifically selected from halogen, methyl or methoxy; X is selected from S, O, N-Me, N-Bn.

5. The use according to claim 3, characterized in that: The molar ratio of the indole-derived aldehyde compound to the thiochromanone-derived compound is selected from 1:1.2 to 1:1.

5.

6. The use according to claim 3, characterized in that: The solvent is ethanol; the catalyst is selected from any one of benzoic acid, p-toluenesulfonic acid, methanesulfonic acid and trifluoromethanesulfonic acid.

7. The use according to claim 3, characterized in that: The amount of the catalyst is 5 mol%; the amount of the solvent is selected from: adding 10 to 20 L of solvent per mole of indole-derived aldehyde compound.

8. The use according to claim 3, characterized in that: The reaction temperature is selected from 40 to 120°C.

9. The use according to claim 1, characterized in that: The indoleazepine-spiro-benzothiophenone compound is specifically selected from one or more of the following structural formulas:

10. The use according to claim 1, characterized in that: The plant pathogenic fungi are selected from one or more of apple rot pathogen, cucumber wilt pathogen, strawberry gray mold pathogen and peanut root rot pathogen.

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