Method for preparing indolo[3,2-a]carbazole alkaloids from 2,3'-biindole

Abstract

The application aims to provide a method for preparing indole [3,2-a] carbazole alkaloids by using 2,3'-biindolyl and alpha-halogenated ketone or alpha-hydroxy ketone as raw materials and reacting under acidic conditions. That is, the mixture of 2,3'-biindolyl and alpha-halogenated ketone or alpha-hydroxy ketone is stirred and reacted in an ethanol solution saturated with hydrogen chloride gas at 80 DEG C, and the indole [3,2-a] carbazole alkaloids are obtained after separation and purification. The method for preparing the indole [3,2-a] carbazole alkaloids has the advantages of easy availability of raw materials, low cost, simple operation, less side reactions, simple post-treatment, high product yield, greatly saved production cost, good economic benefits and suitability for industrial mass production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical synthesis and chemical product synthesis technology, and specifically relates to a method for directly synthesizing indole[3,2-a]carbazole alkaloids under acidic conditions using 2,3'-biindole and α-haloketone or α-hydroxyketone as raw materials. Background Technology

[0002] Indole alkaloids are among the most numerous types of alkaloids discovered to date, and most indole alkaloids possess good biological activities. These include antibacterial, antihypertensive, and platelet aggregation-inhibiting activities, and they are particularly valuable for research in anticancer applications. More than 110 natural indole-carbazole alkaloids have been isolated from nature; for example, Racemosin B is a relatively novel indole[3,2-a]carbazole alkaloid.

[0003]

[0004] Natural products containing indole[3,2-a]carbazole structural units

[0005] Indolecarbazole has become a research hotspot in the field of optoelectronic materials in recent years. This type of substance has been widely reported in fields such as deep blue light-emitting materials (OLED), organic nonlinear optics (NLO) materials, solar cells and organic semiconductor materials, and photorefractive materials.

[0006] The most classic synthetic method for indole[3,2-a]carbazole involves condensation of cyclohexanedione and phenylhydrazine under acid catalysis, followed by rearrangement under heating. This method requires relatively simple raw materials and conditions, but the synthetic steps are lengthy, and it has a narrow substrate scope, making it difficult to prepare products containing multiple substituents.

[0007] Summary of the Invention

[0008] The purpose of this invention is to provide a method for preparing indole[3,2-a]carbazole alkaloids by using 2,3'-binindole and α-haloketone or α-hydroxyketone as raw materials in a one-step reaction under acidic conditions.

[0009] The objective of this invention can be achieved through the following technical solutions:

[0010] The method for preparing indole[3,2-a]carbazole alkaloids is as follows: Under acidic conditions, 2,3'-biindole of general formula (I) reacts with α-haloketone or α-hydroxyketone of general formula (II) in a solvent to obtain indole[3,2-a]carbazole alkaloids of general formula (III), the chemical reaction formula of which is shown below:

[0011]

[0012] Where R 1 Selected from halogens, H, C1-C4 alkyl or alkoxy groups, R 2 Selected from halogens, H, C1-C4 alkyl or alkoxy groups; R 3 Selected from H or C1-C4 alkyl groups; R 4 Selected from H or C1-C4 alkyl groups; R 5 Selected from C1-C4 alkyl or phenyl groups, R 6 Selected from C1-C4 alkyl or phenyl groups; or R 5 and R 6 They connect together to form -(CH2). n - where n = 3-6; X is chlorine, bromine or OH.

[0013] Preferably, where R 1 Selected from fluorine, chlorine, bromine, H, C1-C2 alkyl or alkoxy groups, R 2 Selected from fluorine, chlorine, bromine, H, C1-C2 alkyl or alkoxy groups; R 3 Selected from H or C1-C2 alkyl groups; R 4 Selected from H or C1-C2 alkyl groups; R 5 Selected from C1-C2 alkyl or phenyl groups; R 6 Selected from C1-C2 alkyl or phenyl groups; or R 5 and R 6 They connect together to form -(CH2). n - where n = 3-6; X is chlorine or OH.

[0014] More preferably, where R 1 Selected from fluorine, chlorine, bromine, H, methyl or methoxy, R 2 Selected from fluorine, chlorine, bromine, H, methyl, or methoxy; R 3 Selected from H or methyl; R 4 Selected from H or methyl; R 5 Selected from methyl or phenyl; R 6 Selected from methyl or phenyl; or R 5 and R 6 They connect together to form -(CH2). n - where n = 3-6; X is chlorine or OH.

[0015] The method for preparing indole[3,2-a]carbazole alkaloids, wherein the acidic condition is an inorganic acid (HCl) or an organic acid (TsOH); the solvent is an alcohol solvent or an aromatic solvent; the reaction temperature is 0-120℃; preferably, the acidic condition is an ethanol solution saturated with hydrogen chloride gas, and the reaction temperature is 20-80℃.

[0016] The method for preparing indole[3,2-a]carbazole alkaloids, wherein the molar ratio of 2,3'-biindole of general formula (I) to α-haloketone or α-hydroxyketone of general formula (II) is 1:(0.8-1.2); preferably, the molar ratio of 2,3'-biindole of general formula (I) to α-haloketone or α-hydroxyketone of general formula (II) is 1:(0.9-1.1).

[0017] The method for preparing indole[3,2-a]carbazole alkaloids comprises the following steps: under acidic conditions, the solvent, a mixture of 2,3'-biindole (I) and α-haloketone or α-hydroxyketone (II) is reacted, and after the reaction is completed, the indole[3,2-a]carbazole alkaloids (III) are obtained by separation and purification.

[0018] The specific steps of the method for preparing indole[3,2-a]carbazole alkaloids are as follows: An ethanol solution saturated with hydrogen chloride gas is added to a reactor connected to a reflux condenser. 2,3'-biindole of general formula (I) and α-haloketone or α-hydroxyketone of general formula (II) are reacted. The resulting reaction mixture is stirred at 20-80℃. After the reaction is complete, the solvent is removed by rotary evaporation under reduced pressure. The mixture is then extracted, dried, filtered, and concentrated. Finally, it is purified by column chromatography to obtain the indole[3,2-a]carbazole alkaloids.

[0019] Preferably, the specific operation steps of the above preparation method are as follows: A saturated ethanol solution of hydrogen chloride gas is added to a reactor connected to a reflux condenser. 2,3'-biindole of general formula (I) and α-haloketone or α-hydroxyketone of general formula (II) are added. The reaction mixture is stirred at 80°C. During the reaction, the reaction is continuously monitored by TLC. After the reaction is complete, the solvent is removed by rotary evaporation under reduced pressure. A saturated sodium bicarbonate aqueous solution is added, and the mixture is extracted successively with ethyl acetate and dichloromethane. The extracts are mixed, dried over anhydrous sodium sulfate, filtered, concentrated, and finally purified by column chromatography to obtain the indole[3,2-a]carbazole alkaloid.

[0020] Compared with existing methods for preparing indole[3,2-a]carbazole alkaloids, the present invention has the following advantages:

[0021] (1) In this invention, an ethanol solution saturated with hydrogen chloride gas is used to react 2,3'-biindole of general formula (I) with α-haloketone or α-hydroxyketone of general formula (II) to prepare indole[3,2-a]carbazole alkaloids. The substrates are widely applicable, and various substituted 2,3'-biindoles can react smoothly with various cyclic or chain α-haloketones (or α-hydroxyketones) to prepare a series of indole[3,2-a]carbazole alkaloids, which have potential practical application value.

[0022] (2) The method of the present invention can efficiently synthesize a series of indole[3,2-a]carbazole alkaloids, with mild reaction conditions, simple reaction system, simple operation, and reduced production cost.

[0023] (3) The preparation method described in this invention has good regioselectivity, fewer side reactions, easy product separation, simple post-processing, and achieves good yield (mostly 80%-90%).

[0024] In summary, the technical solution of the present invention has the following beneficial effects:

[0025] The method for preparing indole[3,2-a]carbazole alkaloids uses inexpensive and readily available raw materials and reagents, has a simple reaction system, and is easy to operate. The substrates have wide applicability and good functional group compatibility. The reaction conditions are mild, the reaction rate is fast, the chemical selectivity is good, there are few side reactions, it can be scaled up to the gram level, the subsequent product separation is convenient, and the reaction yield is high (mostly 80-90%). It can realize industrial production and has significant economic and social benefits. Detailed Implementation

[0026] The present invention is described in detail through the following embodiments, but the present invention is not limited to the embodiments.

[0027] Example 1: Synthesis of 5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIa

[0028]

[0029] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.0 mmol of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIa as a white solid in 80% yield.

[0030] 1 H NMR (600MHz, DMSO) δ11.62(s,1H),11.24(s,1H),8.60(d,J=7.7Hz,1H),8.11(d,J=7.9Hz,1H),7.63(d,J=7.9Hz,1H),7.58(d,J=8.0Hz,1H), 7.40–7.35(m,1H),7.34–7.29(m,1H),7.29–7.24(m,1H),7.20–7.15(m ,1H),3.41(t,J=5.9Hz,2H),3.04(t,J=5.8Hz,2H),2.13–1.87(m,4H); 13 C NMR (151MHz, DMSO) δ139.65,139.21,138.84,132.41,129.98,124.46,123.92,122.91,122.30,121 .41,121.27,119.11,119.05,113.36,112.09,111.34,111.23,104.43,28.36,25.12,23.37,22.73.

[0031] Example 2: Synthesis of 5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIa

[0032]

[0033] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.0 mmol of 2-hydroxycyclohexanone IIb. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIa as a white solid in 78% yield.

[0034] Example 3: Synthesis of 4,13-dimethyl-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIb

[0035]

[0036] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ib, and 1.0 mmol of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIb as a white solid in 89% yield.

[0037] 1 H NMR (600MHz, DMSO) δ10.84(s,1H),10.68(s,1H),8.67(dd,J=6.3,2.4Hz,1H),7.95(d,J=7.3Hz,1H),7.32–7.15(m, 2H),7.15–6.96(m,2H),3.40(t,J=5.9Hz,2H),3.12(t,J=5.8Hz,2H),2.73(s,3H),2.66(s,3H),2.15–1.85(m,4H); 13 C NMR (151MHz, DMSO) δ138.92,138.86,138.40,132.67,129.62,124.89,124.52,124.09,122.13,120.71,120.53,1 19.83,119.47,119.07,114.33,112.85,105.42,28.44,25.48,23.41,22.68,18.22,18.01; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2:339.1856; Found:339.1862.

[0038] Example 4: Synthesis of 3,12-dimethyl-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIc

[0039]

[0040] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole Ic (1.0 mmol), and 2-chlorocyclohexanone IIa (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIc as a white solid in 80% yield.

[0041] 1 H NMR (600MHz, DMSO) δ11.40(s,1H),11.03(s,1H),8.46(d,J=7.9Hz,1H),7.94(d,J=8.0Hz,1H),7.40(s,1H),7.36(s,1H),7.16–7 .02(m,1H),7.02–6.90(m,1H),3.40–3.35(m,2H),3.01(t,J=5.7Hz,2H),2.52(s,3H),2.50(d,J=4.2Hz,3H),2.13–1.84(m,4H); 13 C NMR (151MHz, DMSO) δ140.16,139.74,138.48,133.14,132.11,132.00,129.06,122.34,121.10,121.02,120.52,120. 48,120.15,113.42,111.83,111.33,111.29,104.55,28.31,25.17,23.41,22.79,22.21,22.05; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2:339.1856; Found:339.1865.

[0042] Example 5: Synthesis of 2,11-dimethyl-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIId

[0043]

[0044] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Id, and 1.0 mmol of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIId as a white solid in 87% yield.

[0045] 1 H NMR (600MHz, DMSO) δ11.42(s,1H),11.04(s,1H),8.39(s,1H),7.90(s,1H),7.50(d,J=8.0Hz,1H),7.45(d,J=8.1Hz,1H),7.17(d,J=8.1Hz, 1H),7.13(d,J=8.0Hz,1H),3.39(t,J=5.8Hz,2H),3.00(t,J=5.7Hz,2H),2.56(s,3H),2.50(d,J=3.8Hz,3H),2.01(dd,J=28.6,4.6Hz,4H); 13 C NMR (151MHz, DMSO) δ139.03,137.92,137.47,132.76,129.80,127.67,127.42,125.14,124.72,124.07,122.58,121. 42,121.08,113.02,111.80,110.95,110.85,104.23,28.41,25.10,23.38,22.76,21.99,21.81; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2:339.1856; Found:339.1851.

[0046] Example 6: Synthesis of 5,14-dimethyl-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIe

[0047]

[0048] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ie, and 1.0 mmol of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIe as a white solid in 71% yield.

[0049] 1 H NMR (600MHz, CDCl3) δ8.49(d,J=8.0Hz,1H),8.23(d,J=7.9Hz,1H),7.51(d,J=8.0Hz,1H),7.49–7.40(m,3H),7.34–7.2 6(m,2H),4.39(s,3H),4.21(s,3H),3.54(t,J=6.4Hz,2H),3.48(t,J=6.1Hz,2H),2.15–2.02(m,2H),2.02–1.92(m,2H); 13 C NMR (151MHz, CDCl3) δ142.20,141.93,141.17,136.18,132.00,124.93,123.77,123.15,122.29,121.95,121.37,119. 28,119.00,115.20,113.55,109.13,108.97,106.34,35.37,34.15,29.53,28.29,23.47,22.77; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2:339.1856; Found:339.1864.

[0050] Example 7: Synthesis of 3,12-dimethoxy-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIf

[0051]

[0052] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole If, ​​and 1.0 mmol of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIf as a white solid in 86% yield.

[0053] 1 H NMR (600MHz, DMSO) δ11.41(s,1H),11.00(s,1H),8.41(d,J=8.5Hz,1H),7.93(d,J=8.6Hz,1H),7.10(d,J=2.4Hz,1H),7.05(d,J=2.3Hz,1H),6.8 8(dd,J=8.5,2.3Hz,1H),6.78(dd,J=8.6,2.4Hz,1H),3.87(s,3H),3.86(s,3H),3.33(d,J=5.8Hz,2H),2.99(t,J=5.9Hz,2H),2.08–1.84(m,4H); 13 C NMR (151MHz, DMSO) δ157.53,156.73,140.94,140.60,138.00,131.70,127.76,121.96,121.85,118.61,116.31,113 .63,111.75,107.77,107.49,104.64,95.34,95.27,55.72,55.65,28.17,25.09,23.43,22.82; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2 O2:371.1754; Found:371.1749.

[0054] Example 8: Synthesis of 2,11-dimethoxy-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole III g

[0055]

[0056] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1 g (1.0 mmol) of 2,3'-biindole, and 1 g (1.0 mmol) of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give III g as a pale yellow solid, in 88% yield.

[0057] 1 H NMR (600MHz, DMSO) δ11.42(s,1H),11.00(s,1H),8.14(d,J=2.4Hz,1H),7.61(d,J=2.4Hz,1H),7.53(d,J=8.6Hz,1H),7.46(d,J=8.7Hz,1H),6.99( ddd,J=12.0,8.6,2.4Hz,2H),3.95(s,3H),3.87(s,3H),3.40(t,J=5.9Hz ,2H),2.99(t,J=5.8Hz,2H),2.03(d,J=4.4Hz,2H),1.98(d,J=4.3Hz,2H); 13 C NMR (151MHz, DMSO) δ153.87,153.48,139.62,134.48,134.05,133.36,129.91,125.00,122.71,113.05,112.89,111. 84,111.81,111.38,111.18,105.30,104.59,104.50,56.46,56.14,28.17,25.06,23.41,22.71; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2 O2:371.1754; Found:371.1760.

[0058] Example 9: Synthesis of 3,12-difluoro-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIh

[0059]

[0060] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole Ih (1.0 mmol), and 2-chlorocyclohexanone IIa (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIh as a white solid in 85% yield.

[0061] 1 H NMR (600MHz, DMSO) δ11.84(s,1H),11.42(s,1H),8.62(dd,J=8.5,5.5Hz,1H),8.03(dd,J=8.6,5.5Hz,1H),7.38(ddd,J=15.6,9.9,2 .4Hz,2H),7.17(td,J=9.7,2.4Hz,1H),7.00(td,J=9.6,2.4Hz,1H),3.34(t,J=5.6Hz,2H),3.04(t,J=5.5Hz,2H),2.15–1.84(m,4H); 13 C NMR (151MHz, DMSO) δ161.39,160.72,159.82,159.15,140.28,140.20,139.95,139.87,139.26,139.25,132.59,132.58,129.40,122.35,122.2 9,122.22,121.24,119.01,113.43,112.52,107.04,106.88,106.81,10 6.66,104.26,97.87,97.70,97.68,97.51,28.16,25.07,23.26,22.65; 19 F NMR(565MHz,DMSO)δ-118.12,-118.13,-118.14,-118.15,-118.16,-118.17, -119.58,-119.59,-119.60,-119.61,-119.61,-119.62; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2 O2:347.1354; Found:347.1355.

[0062] Example 10: Synthesis of 3,12-dichloro-5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIi

[0063]

[0064] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole IIi (1.0 mmol), and 2-chlorocyclohexanone IIa (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to obtain IIIi as a grayish-white solid in 84% yield.

[0065] 1 H NMR (600MHz, DMSO) δ11.48(s,1H),8.10(d,J=8.5Hz,1H),7.54(d,J=1.9Hz,1H),7.32–7.09(m,3H),7.08(d,J=8.0Hz,1H),6.98(d,J= 7.4Hz,1H),6.54(s,1H),3.30(dd,J=14.2,6.9Hz,2H),2.45(t,J=6.0Hz,2H),1.92(ddd,J=17.9,11.2,6.2Hz,2H),1.82–1.52(m,2H); 13 C NMR(151MHz,DMSO)δ141.19,138.54,132.71,132.64,132.42,129.74,126.46,124.14,12 2.03,120.34,119.00,110.82,110.59,28.45,27.61,23.22,22.83; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2 O2:379.0763; Found:379.0756.

[0066] Example 11: Synthesis of 6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole IIIj

[0067]

[0068] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole Ia (1.0 mmol), and 2-chlorocyclopentanone IIc (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIj as a white solid in 80% yield.

[0069] 1 H NMR (600MHz, CDCl3) δ8.17(brs,1H),8.02(d,J=7.8Hz,1H),7.31(ddd,J=13.6,10.3,4.3Hz,2H),7.24(dd,J=7.5,1.5Hz,1H),7.21–7.14(m ,2H),6.85(td,J=7.4,1.1Hz,1H),6.80(dd,J=8.0,0.8Hz,1H),3.42(t,J=7.4Hz,2H),3.06(dd,J=11.4,7.0Hz,2H),2.28(p,J=7.3Hz,2H); 13 C NMR (151MHz, CDCl3) δ143.82,139.93,137.07,136.75,135.94,131.40,128.81,125.46,124.73,123.59,12 2.97,121.85,119.93,119.75,119.33,119.00,115.78,110.68,32.34,32.07,25.74; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 17 N2:297.1386; Found:297.1380.

[0070] Example 12: Synthesis of 4,12-dimethyl-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole IIIk

[0071]

[0072] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ib, and 1.0 mmol of 2-chlorocyclopentanone IIc. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIk as a white solid in 85% yield.

[0073] 1 H NMR (600MHz, DMSO) δ11.07(s,1H),10.88(s,1H),8.77–8.60(m,1H),7.83(dd,J=6.7,1.8Hz,1H),7.17(d,J=5.1Hz,2H), 7.14–6.99(m,2H),3.49(t,J=7.4Hz,2H),3.28(t,J=7.4Hz,2H),2.73(s,3H),2.65(s,3H),2.39(dd,J=14.7,7.4Hz,2H); 13 C NMR (151MHz, DMSO) δ138.86,138.46,136.51,135.60,133.77,124.78,124.39,124.10,122.09,120.85,120.34,1 19.80,119.60,118.95,118.60,117.87,112.65,106.32,32.74,30.32,25.60,18.18,17.90; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 17 N2: 325.1699; Found: 325.1701.

[0074] Example 13: Synthesis of 3,11-dimethyl-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole III

[0075]

[0076] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole Ic (1.0 mmol), and 2-chlorocyclopentanone IIc (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIc as a yellow solid, in 83% yield.

[0077] 1 H NMR (600MHz, CDCl3) δ11.41(s,1H),11.20(s,1H),8.46(d,J=7.9Hz,1H),7.84(d,J=7.8Hz,1H),7.39(s,1H),7.33(s,1H),7.1 5–7.04(m,1H),7.04–6.90(m,1H),3.45(t,J=7.4Hz,2H),3.19(t,J=7.3Hz,2H),2.52(s,3H),2.51(s,3H),2.42–2.24(m,2H); 13 C NMR (151MHz, DMSO) δ140.14,139.76,136.05,134.99,133.25,133.22,132.39,121.89,121.00,120.64,120.4 4,120.21,120.00,117.73,111.79,111.36,111.23,105.53,32.64,30.00,25.62,22.17; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 17 N2: 325.1699; Found: 325.1708.

[0078] Example 14: Synthesis of 2,10-dimethyl-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole IIIm

[0079]

[0080] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole Id (1.0 mmol), and 2-chlorocyclopentanone IIc (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIm as a pale yellow solid in 76% yield.

[0081] 1 H NMR (600MHz, DMSO) δ11.43(s,1H),11.21(s,1H),8.40(s,1H),7.78(s,1H),7.50(d,J=8.1Hz,1H),7.43(d,J=8.1Hz,1H),7.2 3–7.15(m,1H),7.15–7.05(m,1H),3.48(d,J=7.4Hz,2H),3.18(d,J=7.4Hz,2H),2.57(s,3H),2.50(s,3H),2.42–2.26(m,2H); 13 CNMR(151MHz,DMSO)δ137.91,137.49,136.61,135.68,133.89,127.65,125.18,124.45,124.28,122.66,121. 09,120.24,117.67,111.43,110.96,110.84,105.22,32.78,29.96,25.54,21.84,21.81; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 17 N2: 325.1699; Found: 325.1694.

[0082] Example 15: Synthesis of 2,10-dimethyl-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole IIIn

[0083]

[0084] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ig, and 1.0 mmol of 2-chlorocyclopentanone IIc. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted with ethyl acetate and dichloromethane, respectively. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIn as a yellow solid in 90% yield.

[0085] 1 H NMR (600MHz, DMSO) δ11.42(s,1H),11.17(s,1H),8.13(d,J=2.4Hz,1H),7.50(dd,J=15.2,5.5Hz,2H),7.43(d,J=8.6Hz,1H),6 .98(ddd,J=15.7,8.6,2.4Hz,2H),3.95(s,3H),3.87(s,3H),3.50(t,J=7.4Hz,2H),3.17(t,J=7.4Hz,2H),2.45–2.24(m,3H); 13 CNMR(151MHz,DMSO)δ153.82,153.70,137.18,135.87,134.46,134.04,124.59,122.78,117.64,112.88, 111.67,111.52,105.46,104.54,103.76,99.67,56.48,56.06,32.67,29.92,25.48; HRMS(ESI)m / z:[M+H] + calcd for C 23 H 21 N2O2:357.1598; Found:357.1605.

[0086] Example 16: Synthesis of 4,12-difluoro-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole III

[0087]

[0088] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ij, and 1.0 mmol of 2-chlorocyclopentanone IIc. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIo as a white solid in 88% yield.

[0089] 1 H NMR(600MHz,DMSO)δ12.00(s,1H),11.88(s,1H),8.82–8.67(m,1H),7.82(d,J=7.4Hz,1 H),7.37–7.02(m,4H),3.48(t,J=7.4Hz,2H),3.27(t,J=7.4Hz,2H),2.44–2.20(m,2H); 13 C NMR (151MHz, DMSO) δ150.10,149.98,148.50,148.38,137.35,136.77,133. 89,127.93,127.89,127.02,126.93,126.88,126.79,126.10,126.06,119. 89,119.85,119.45,119.41,118.26,118.24,116.49,116.48,112.64,112.62,109.45,109.34,109.02,108.91,106.18,106.16,32.70,30.17,25.44; 19 F NMR(565MHz, DMSO)δ-131.72,-131.72,-131.74,-131.74,-132.98,-132.99,-133.00,-133.01; HRMS(ESI)m / z:[M+H] + calcd for C 23 H 21 N2O2:333.1598; Found:333.1589.

[0090] Example 17: Synthesis of 3,11-difluoro-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole IIIp

[0091]

[0092] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole Ih (1.0 mmol), and 2-chlorocyclopentanone IIc (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIp as a white solid in 89% yield.

[0093] 1 H NMR (600MHz, DMSO) δ11.83(s,1H),11.57(s,1H),8.60(dd,J=8.5,5.5Hz,1H),7.93(dd,J=8.5,5.5Hz,1H),7.35(ddd,J=19.3,9.9,2.3H z,2H),7.15(td,J=9.7,2.3Hz,1H),7.02(ddd,J=10.0,8.7,2.3Hz,1H),3.44(t,J=7.4Hz,2H),3.21(t,J=7.4Hz,2H),2.44–2.20(m,2H); 13 C NMR (151MHz, DMSO) δ161.40,160.99,159.83,159.43,140.17,140.09,139.96,139.88,136.79,135.33,133.72,133.70,122.24,122.17,12 1.26,121.19,120.76,119.07,118.48,111.76,107.06,106.97,106. 90,106.82,105.24,97.84,97.80,97.67,97.63,32.51,29.91,25.54; 19 F NMR(565MHz,DMSO)δ-118.12,-118.13,-118.14,-118.15,-118.16,-118.17,-11 9.08,-119.09,-119.09,-119.10,-119.11,-119.12; HRMS(ESI)m / z:[M+H]+calcd for C 23 H 21 N2O2:333.1598; Found:333.1593.

[0094] Example 18: Synthesis of 3,11-dichloro-6,7,8,13-tetrahydro-5H-cyclopentano[a]indole[3,2-c]carbazole IIIq

[0095]

[0096] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 2,3'-biindole IIi (1.0 mmol), and 2-chlorocyclopentanone IIc (1.0 mmol). The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIq as a white solid in 81% yield.

[0097] 1 H NMR (600MHz, DMSO) δ11.87(s,1H),11.65(s,1H),8.59(d,J=8.3Hz,1H),7.97(d,J=8.3Hz,1H),7.58(dd,J=14.2,1.9Hz,2H) ,7.32(dd,J=8.3,1.9Hz,1H),7.21(dd,J=8.2,1.9Hz,1H),3.47(t,J=7.4Hz,2H),3.21(t,J=7.4Hz,2H),2.44–2.30(m,2H); 13 CNMR(151MHz,DMSO)δ140.24,139.94,137.04,136.50,133.73,128.64,127.87,122.76,122.37,121.56,12 1.05,119.48,119.29,118.77,111.64,110.93,110.88,105.04,32.61,29.90,25.51; HRMS(ESI)m / z:[M+H] + calcd for C 21 H 15 Cl2N2:365.0607; Found:365.0612.

[0098] Example 19: Synthesis of 6,7,8,9,10,15-hexahydro-5H-cycloheptano[a]indole[3,2-c]carbazole IIIr

[0099]

[0100] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.0 mmol of 2-chlorocycloheptanone IId. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to obtain IIIr as a white solid.

[0101] 1 H NMR (600MHz, DMSO) δ11.58(s,1H),11.27(s,1H),8.61(d,J=7.7Hz,1H),8.25(d, J=8.0Hz,1H),7.64(d,J=7.8Hz,1H),7.56(d,J=8.0Hz,1H),7.40–7.35(m,1H),7. 34–7.30(m,1H),7.28–7.24(m,1H),7.19–7.14(m,1H),3.70–3.52(m,2H),3.31– 3.19(m,2H),1.96(d,J=4.9Hz,2H),1.81(d,J=4.6Hz,2H),1.73(d,J=4.7Hz,2H); 13 C NMR (151MHz, DMSO) δ140.11,139.30,138.69,136.76,132.80,124.18,124.07,123.15,122.50,121.21,121.17,1 19.08,118.90,118.46,113.33,111.46,111.06,104.66,32.53,30.60,28.22,27.99,27.23; HRMS(ESI)m / z:[M+H] + calcd for C 23 H 21 N2: 325.1699; Found: 325.1707.

[0102] Example 20: Synthesis of 5,6,7,8,9,10,11,16-octahydrocyclooctano[a]indole[3,2-c]carbazole IIIs

[0103]

[0104] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.0 mmol of 2-chlorocyclooctanone IIe. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to obtain IIIs as a white solid.

[0105] 1 H NMR (600MHz, DMSO) δ11.62(s,1H),11.31(s,1H),8.61(d,J=7.7Hz,1H),8.12(d, J=7.9Hz,1H),7.69–7.63(m,1H),7.58(d,J=8.0Hz,1H),7.40–7.36(m,1H),7.32 (t,J=7.5Hz,1H),7.26(dd,J=11.3,4.2Hz,1H),7.22–7.17(m,1H),3.51(s,2H), 3.30–3.18(m,2H),1.93(d,J=5.2Hz,2H),1.78(s,2H),1.44(s,2H),1.31(s,2H); 13 C NMR (151MHz, DMSO) δ139.90,139.25,138.63,133.29,133.03,124.00,123.95,123.03,122.45,121.20,120.92,119. 30,118.92,115.90,113.03,111.39,111.20,104.92,31.09,29.64,27.84,26.82,26.23,26.13; HRMS(ESI)m / z:[M+H] + calcd for C 24 H 23 N2:339.1856; Found:339.1563.

[0106] Example 21: Synthesis of 6,7-dimethyl-5,12-dihydroindole[3,2-a]carbazole IIIt

[0107]

[0108] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.0 mmol of 3-chloro-2-butanone IIf. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIf as a white solid, in a yield of 66%.

[0109] 1 H NMR (600MHz, DMSO) δ11.61(s,1H),11.26(s,1H),8.61(d,J=7.7Hz,1H),8.20(d,J=7.9Hz,1H),7.64(d,J=7.9Hz,1H),7.59(d,J=8 .0Hz,1H),7.38(t,J=7.5Hz,1H),7.33(t,J=7.5Hz,1H),7.26(t,J=7.4Hz,1H),7.19(t,J=7.5Hz,1H),2.90(s,3H),,2.63(s,3H); 13 C NMR (151MHz, DMSO) δ139.84,139.65,139.28,132.50,128.80,124.60,124.03,123.06,122.42,121.3 5,121.28,119.14,119.01,114.28,111.28,111.23,110.42,104.60,17.09,13.69; MS(ESI)m / z:[M+H] + calcd for C 20 H 17 N2:285.1; Found:285.4.

[0110] Example 22: Synthesis of 4,6,7,11-tetramethyl-5,12-dihydroindole[3,2-a]carbazole IIIu

[0111]

[0112] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ib, and 1.0 mmol of 3-chloro-2-butanone IIf. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIu as a white solid in 69% yield.

[0113] 1 H NMR (600MHz, CDCl3) δ8.30(s,1H),8.17–8.10(m,1H),7.97(d,J=7.6Hz,1H),7.92(s,1H),7.29(t ,J=7.4Hz,1H),7.23(dd,J=14.2,6.9Hz,3H),2.95(s,3H),2.69(s,3H),2.65(s,3H),2.62(s,3H); 13 C NMR (151MHz, CDCl3) δ138.69,138.28,137.85,132.46,129.37,124.77,124.48,124.02,122.34,119.94,119.7 6,119.65,119.48,119.35,117.95,115.94,110.25,105.20,17.09,17.03,16.71,13.19; HRMS(ESI)m / z:[M+H] + calcd forC 22 H 21 N2: 313.1699; Found: 313.1707.

[0114] Example 23: Synthesis of 3,10-difluoro-6,7-dimethyl-5,12-dihydroindole[3,2-a]carbazole IIIv

[0115]

[0116] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ij, and 1.0 mmol of 3-chloro-2-butanone IIf. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIv as a white solid in 67% yield.

[0117] 1 H NMR (600MHz, CDCl3) δ8.58(s,1H),8.45(s,1H),7.60(d,J=8.0Hz,1H),7.44(d,J=2.5Hz,1H),7.24(d,J=7.9Hz,1H),7.17(td,J=7.9,4.8Hz ,1H),7.08(td,J=7.9,4.8Hz,1H),7.02(dd,J=11.0,7.9Hz,1H),6.94(dd,J=11.0,7.8Hz,1H),2.12(d,J=1.5Hz,3H),1.96(d,J=1.5Hz,3H); 13 C NMR (151MHz, CDCl3) δ150.55,150.14,148.92,148.52,131.52,131.48,129.92,1 29.23,128.92,128.89,125.66,124.70,124.61,124.16,123.94,123.85,121.37 ,121.33,120.43,120.39,115.25,115.22,115.09,115.07,114.03,114.01,109. 49,109.48,107.92,107.81,106.98,106.87,23.87,20.99; HRMS(ESI)m / z:[M+H] + calcd for C 20 H 15 F2N2:321.1198; Found:321.1204.

[0118] Example 24: Synthesis of 2,9-dibromo-6,7-dimethyl-5,12-dihydroindole[3,2-a]carbazole IIIw

[0119]

[0120] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ik, and 1.0 mmol of 3-chloro-2-butanone IIf. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIw as a white solid in 50% yield.

[0121] 1 H NMR (600MHz, DMSO) δ11.93(s,1H),11.53(s,1H),8.83(d,J=1.8Hz,1H),8.28(d,J=1.8Hz,1H),7.63–7.42(m,4H),2.87(s,3H),2.61(s,3H); 13 C NMR (151MHz, DMSO) δ140.62,138.50,138.02,132.93,129.96,126.60,126.30,125.64,124.05,123.46,123 .33,113.67,113.19,113.07,111.60,111.49,111.21,103.73,100.00,17.05,13.61; HRMS(ESI)m / z:[M+H] + calcd for C 20 H 15 Br2N2:440.9597; Found:440.9591.

[0122] Example 25: Synthesis of 6,7-diphenyl-5,12-dihydroindole[3,2-a]carbazole IIIx

[0123]

[0124] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.0 mmol of hydroxyketone II. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted with ethyl acetate and dichloromethane, respectively. The extracts were mixed, dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the mixture was purified by column chromatography to obtain IIIx as a white solid.

[0125] 1H NMR (600MHz, DMSO) δ11.85 (s, 1H), 10.73 (s, 1H), 8.71 (d, J = 7.8Hz, 1H), 7.61 (dd, J=19.3,8.0Hz,2H),7.48–7.12(m,13H),6.87–6.74(m,1H),6.53(d,J=7.9Hz,1H); 13 CNMR(151MHz,DMSO)δ140.44,140.18,139.79,138.26,137.85,133.68,133.34,131.63,130.76,128.54,128.41,127.3 1,126.91,124.57,124.10,123.62,121.86,121.48,120.57,119.29,118.87,117.74,113.95,111.94,111.42,106.03.

[0126] Example 26: Synthesis of 5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIa

[0127]

[0128] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 0.8 mmol of 2-chlorocyclohexanone IIa. The reaction mixture was stirred at 80 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to give IIIa as a white solid in 78% yield.

[0129] Example 27: Synthesis of 5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIa

[0130]

[0131] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of ethanol solution saturated with hydrogen chloride gas, 1.0 mmol of 2,3'-biindole Ia, and 1.2 mmol of 2-hydroxycyclohexanone IIb. The reaction mixture was stirred at 20 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the solution was purified by column chromatography to obtain IIIa in 51% yield.

[0132] Example 28: Synthesis of 5,6,7,8,9,14-hexahydrobenzo[a]indole[3,2-c]carbazole IIIa

[0133]

[0134] To a 10 mL two-necked flask connected to a reflux condenser, add 2 mL of toluene, p-toluenesulfonic acid (0.2 mmol), 2,3'-biindole Ia (1.0 mmol), and 2-chlorocyclohexanone IIa (0.8 mmol). The reaction mixture was stirred at 110 °C, and the reaction was continuously monitored by TLC. After the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, and 10 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was then extracted successively with ethyl acetate and dichloromethane. The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Finally, the extract was purified by column chromatography to obtain IIIa in a yield of 67%.

Claims

1. A method for preparing indole[3,2-a]carbazole alkaloids from 2,3'-biindole, characterized in that, Under acidic conditions, 2,3'-biindole of general formula (I) reacts with α-haloketone or α-hydroxyketone of general formula (II) in a solvent to give indole[3,2-a]carbazole alkaloids of general formula (III), as shown in the following chemical reaction formula: Where R 1 Selected from fluorine, chlorine, bromine, H, methyl or methoxy, R 2 Selected from fluorine, chlorine, bromine, H, methyl, or methoxy; R 3 Selected from H or methyl; R 4 Selected from H or methyl; R 5 Selected from methyl or phenyl; R 6 Selected from methyl or phenyl; or R 5 and R 6 They connect together to form -(CH2). n - where n=3-6; X is chlorine or OH; the acidic condition is HCl or TsOH; the solvent is an alcohol solvent or an aromatic solvent; when the acidic condition is HCl, specifically: add an ethanol solution saturated with hydrogen chloride gas, the reaction temperature is 20-80℃, and the operation steps are as follows: add an ethanol solution saturated with hydrogen chloride gas to a reactor connected to a reflux condenser, 2,3'-biindole of general formula (I) and α-haloketone or α-hydroxyketone of general formula (II), stir the resulting reaction mixture at 20-80℃, when the reaction is complete, remove the solvent by rotary evaporation under reduced pressure, extract, dry, filter and concentrate, and finally separate and purify by column chromatography to obtain the indole[3,2-a]carbazole alkaloid.

2. The method for preparing indole[3,2-a]carbazole alkaloids as described in claim 1, characterized in that: The molar ratio of 2,3'-biindole represented by general formula (I) to α-haloketone or α-hydroxyketone represented by general formula (II) is 1: (0.8-1.2).

3. The method for preparing indole[3,2-a]carbazole alkaloids as described in claim 2, characterized in that: The molar ratio of 2,3'-biindole represented by general formula (I) to α-haloketone or α-hydroxyketone represented by general formula (II) is 1: (0.9-1.1).

4. The method for preparing indole[3,2-a]carbazole alkaloids as described in claim 1, characterized in that: The specific operating steps are as follows: Add an ethanol solution saturated with hydrogen chloride gas to a reactor connected to a reflux condenser, 2,3'-biindole of general formula (I) and α-haloketone or α-hydroxyketone of general formula (II), stir the reaction mixture at 80°C, continuously monitor the reaction with TLC during the reaction, remove the solvent by rotary evaporation under reduced pressure after the reaction is completed, add saturated sodium bicarbonate aqueous solution, extract with ethyl acetate and dichloromethane successively, mix the extracts, dry with anhydrous sodium sulfate, filter, concentrate, and finally purify by column chromatography to obtain the indole[3,2-a]carbazole alkaloid.

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