Naphthoquinone polycyclic derivative, preparation method and application thereof

文档序号：316961 发布日期：2021-11-30 浏览：22次中文

阅读说明：本技术 萘醌多并环衍生物及其制备方法及其用途 (Naphthoquinone polycyclic derivative, preparation method and application thereof ) 是由王继宇汪蓓于 2021-09-24 设计创作，主要内容包括：本发明涉及药物化学技术领域,公开了萘醌多并环衍生物及其制备方法及其用途。所述萘醌多并环衍生物的结构通式如式I所示：R-(1)为Ph-、Br-、OH-、H-；R-(2)为-OMe、Me-、-CN、-NO-(2)、F-、Cl-、Br-、H-、-COOH；R-(3)为烷基、烯烃基、苄基,烷基的碳原子个数为1～4,烯烃基的碳原子个数为3～4；R-(4)＝R-(5)＝烷基或取代烷基,芳基,取代芳基,杂芳基,烷基的碳原子个数为1～6；或者R-(4)为环己基；R-(5)为H、苯基。本申请制备得到的萘醌多并环衍生物,具有一定的生物活性,可作为潜在药物或候选药物分子用于抗癌、抗肿瘤、抗炎、抗菌等方面的研究,同时具有良好的光物理性质,可应用于荧光材料领域。(The invention relates to the technical field of medicinal chemistry, and discloses a naphthoquinone polycyclic derivative, and a preparation method and application thereof. The structural general formula of the naphthoquinone polycyclic derivative is shown as a formula I: R 1 is Ph-, Br-, OH-or H-; r 2 is-OMe, Me-, -CN, -NO 2 、F‑、Cl‑、Br‑、H‑、‑COOH；R 3 Is alkyl, alkenyl or benzyl, the number of carbon atoms in the alkyl group is 1-4, and the carbon atoms in the alkenyl groupThe number of atoms is 3-4; r 4 ＝R 5 The carbon atom number of the alkyl is 1-6; or R 4 Is cyclohexyl; r 5 Is H and phenyl. The naphthoquinone polycyclic derivative prepared by the method has certain biological activity, can be used as a potential drug or a candidate drug molecule for research on the aspects of cancer resistance, tumor resistance, inflammation resistance, bacteria resistance and the like, has good photophysical properties, and can be applied to the field of fluorescent materials.)

1. The naphthoquinone polycyclic derivative is characterized in that the structural general formula of the naphthoquinone polycyclic derivative is shown as a formula I:

in the formula I, the compound is shown in the specification,

R₁is Ph-, Br-, OH-, H-or Me-;

R₂is-OMe, Me-, -CN, -NO₂、F-、Cl-、Br-、H-、-COOH；

R₃Is alkyl, alkenyl or benzyl, the number of carbon atoms of the alkyl is 1-4, and the number of carbon atoms of the alkenyl is 3-4; r₄＝R₅The carbon atom number of the alkyl is 1-6;

or R₄Is cyclohexyl; r₅Is H and phenyl.

2. The naphthoquinone polyacyclo derivative according to claim 1,

R₃is methyl, n-propyl, n-butyl, benzyl or allyl;

R₄＝R₅methyl, ethyl, n-propyl, cyclohexyl, (2- (2- (2-methoxyethoxy) ethoxy) ethyl, 2-maleimidoethyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-bromophenyl, 4-cyanophenyl, 4-methoxycarbonylphenyl, 2-methylphenyl, 2-methoxycarbonylthienyl;

or R₄Is cyclohexyl, R₅Is H and phenyl.

3. A process for preparing naphthoquinone polya-ring derivatives as claimed in claim 1 or 2, comprising the steps of:

and (3) adding naphthoquinone, indole and maleimide into a reaction container, adding a catalyst and a solvent, and reacting, separating and purifying to obtain the naphthoquinone polycyclic derivative.

4. The process for preparing naphthoquinone polycyclic derivative according to claim 3, wherein the chemical reaction formula is,

5. the method for preparing naphthoquinone polycyclic derivative according to claim 3, wherein the molar ratio of naphthoquinone to indole to maleimide is 1: 0.5-3: 0.5-4.

6. The method for preparing naphthoquinone polycyclic derivative according to claim 3, wherein the molar ratio of naphthoquinone to catalyst is 1: 0.01-0.5.

7. The method for preparing naphthoquinone polyatomic derivative according to any one of claims 3 to 6, wherein the catalyst includes TsOH H₂O、CuSO₄·5H₂O、Cu(OTf)₂、Ni(OTf)₂、Pd(OAc)₂、Fe(acac)₃、FeCl₃、HCl、B(C₅F₆)₃、CoCl₂、Ni(acac)₂、C₆H₅B(OH)₂、BF₃·OEt₂At least one of (1).

8. The method for preparing naphthoquinone polyacyclo derivative as claimed in any one of claims 3 to 6, wherein the solvent comprises EtOH, H₂O、THF、toluene、(CH₂OH)₂At least one of MeCN, DMF, DCE and DMSO.

9. The method for preparing naphthoquinone polyatomic derivative according to any one of claims 3 to 6, wherein the reaction temperature is room temperature to 120 ℃ and the reaction time is 6-30 hours.

10. Use of the naphthoquinone polya-ring derivative according to claim 1, in fluorescent materials and pharmaceutical materials.

Technical Field

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a naphthoquinone polycyclic derivative, and a preparation method and application thereof.

Background

1, 4-naphthoquinone is a structural scaffold widely distributed in natural products, drugs. Some polycyclic compounds containing quinone structures attract the attention of synthetic chemists due to the fact that the compounds have various biological activities such as cancer resistance, anti-inflammation and malaria resistance, for example, (1) Calothrix B separated from blue algae Calothrix has biological activities of antimalarial and killing Hela cancer cells; (2) the Kinamycin series natural products have the function of resisting the proliferation of cancer cells; (3) the marine natural product Jorunnamycin A shows obvious growth inhibition on human colon and breast cancer cell lines; (4) metabolic isolation product Hygr ℃insof streptomycete has anti-inflammatory activity. Based on the above, the synthesis of the naphthoquinone polycyclic derivative with a complex structure has extremely important significance.

The multi-component polycyclic compound has the potential of becoming a fluorescent probe and a chemoreceptor, and a small amount of documents report the chemoreceptor based on quinone structures for identifying certain anions and cations. Therefore, the synthesis of the quinone derivative with good fluorescence property is very important, and the quinone derivative can be applied to a plurality of fields of environmental science, medicine, cell biology and the like.

In the last decade, reports on simple functionalization of naphthoquinones have emerged, such as alkylation, arylation, amination, trifluoromethylation, etc. of naphthoquinones. However, few reports have been made on the construction of naphthoquinone polycyclic derivatives based on this basic structural unit. At present, the method for constructing the naphthoquinone polycyclic derivative mainly comprises the following steps: (1) construction of cyclic derivatives by the formation of intermolecular continuous C-C and C-X bonds ((a) J.org.chem.2013, 78,10560, (b) J.org.chem.2017,82,8309.); (2) naphthoquinone derivatives having a complex cyclic structure are synthesized by intermolecular cycloaddition reaction ((c) org.Lett.2014,16,1286, (d) J.org.chem.2019,84,9929, (e) org.Lett.2020,22,265, (f) org.Lett.2019, 21,4549.). The existing synthesis method mainly has the following problems: (1) pre-functionalization is required; (2) the target product is required to be synthesized through multi-step reaction; (3) expensive metal catalysts are used, and the reaction conditions are severe. Therefore, it is of great importance to find new methods for constructing naphthoquinone polycyclic compounds.

Disclosure of Invention

< problems to be solved by the present invention >

The method realizes the serial cyclization reaction of naphthoquinone, indole and maleimide by a one-pot method under the condition of not pre-functionalizing a substrate.

< technical solution adopted in the present invention >

Aiming at the technical problems, the invention provides naphthoquinone polycyclic derivatives, a preparation method and application thereof.

Specifically, the method comprises the following steps:

the invention provides a naphthoquinone polycyclic derivative, wherein the structural general formula of the naphthoquinone polycyclic derivative is shown as a formula I:

in the formula I, the compound is shown in the specification,

R₁is Ph-, Br-, OH-or Me-;

R₂is-OMe, Me-, -CN, -NO₂、F-、Cl-、Br-、H-、-COOH；

R₃Is alkyl, alkenyl or benzyl, the number of carbon atoms of the alkyl is 1-4, and the number of carbon atoms of the alkenyl is 3-4; r₄＝R₅The carbon atom number of the alkyl is 1-6;

or R₄Is cyclohexyl; r₅Is H and phenyl.

Further, R₃Is methyl, n-propyl, n-butyl, benzyl or allyl;

or R₄Is cyclohexyl, R₅Is H and phenyl.

The invention provides a preparation method of naphthoquinone polycyclic derivative, which comprises the following steps:

Thirdly, the invention provides the application of the naphthoquinone polycyclic derivative in fluorescent materials and medical materials.

< advantageous effects achieved by the present invention >

(1) The novel naphthoquinone polycyclic derivative provided by the invention has certain biological activity, and can be used as a potential drug or a candidate drug molecule for research on the aspects of cancer resistance, tumor resistance, inflammation resistance, bacteria resistance and the like. The compound obtained by the invention has good photophysical properties, can be applied to the field of fluorescent materials, and has the potential of becoming a fluorescent probe and a fluorescent marker. (3) The synthesis method provided by the invention has the advantages of simple operation, low cost, high yield, wide substrate adaptability and the like.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

The invention provides a naphthoquinone polycyclic derivative, wherein the structural general formula of the naphthoquinone polycyclic derivative is shown as a formula I:

in the formula I, the compound is shown in the specification,

R₁is Ph-, Br-, OH-or Me-;

R₂is-OMe, Me-, -CN, -NO₂、F-、Cl-、Br-、H-、-COOH；

R₃Is an alkyl group, an alkenyl group,Benzyl, wherein the number of carbon atoms of the alkyl group is 1-4, and the number of carbon atoms of the alkenyl group is 3-4; r₄＝R₅The carbon atom number of the alkyl is 1-6;

or R₄Is cyclohexyl; r₅Is H and phenyl.

Further, R₃Is methyl, n-propyl, n-butyl, benzyl or allyl;

or R₄Is cyclohexyl, R₅Is H and phenyl.

The invention provides a preparation method of naphthoquinone polycyclic derivative, which comprises the following steps:

In the invention, the chemical reaction formula is,

in the invention, the molar ratio of naphthoquinone to indole to maleimide is 1: 0.5-3: 0.5-4.

In the invention, the molar ratio of the naphthoquinone to the catalyst is 1: 0.01-0.5.

In the present invention, the catalyst comprises TsOH. H₂O、CuSO₄·5H₂O、Cu(OTf)₂、Ni(OTf)₂、 Pd(OAc)₂、Fe(acac)₃、FeCl₃、HCl、B(C₅F₆)₃、CoCl₂、Ni(acac)₂、C₆H₅B(OH)₂、 BF₃·OEt₂At least one of (1).

In the present invention, the solvent includes EtOH, H₂O、THF、toluene、(CH₂OH)₂At least one of MeCN, DMF, DCE and DMSO.

In the invention, the reaction temperature is between room temperature and 120 ℃, and the reaction time is 6-30 h.

In the invention, the separation and purification mode is extraction, column chromatography or recrystallization.

Thirdly, the invention provides the application of the naphthoquinone polycyclic derivative, which is applied to fluorescent materials and medicinal materials.

< example >

Example 1 Synthesis of naphthoquinone polycyclic derivative 4a

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid 4a, and the yield is 80%.

Red solid, melting point: 282 ℃ and 283 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.14(d, J＝8.0Hz,1H),8.21–8.15(m,2H),7.88–7.81(m,2H),7.47(ddd,J＝ 8.3,7.2,1.2Hz,1H),7.33–7.22(m,6H),6.89(d,J＝8.4Hz,1H),6.75(t,J ＝7.6Hz,1H),6.65–6.57(m,4H),4.28(d,J＝8.5Hz,2H),4.05(d,J＝8.5 Hz,2H),3.42(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ194.1,178.5,174.7, 172.0,159.0,153.5,137.3,136.0,135.4,135.2,134.1,131.7,129.7,129.5, 129.1,127.8,126.7,126.6,119.5,117.2,116.4,107.8,72.7,51.9,46.0,41.8, 28.6.HRMS(ESI):m/z:[M+Na]⁺Calcd.for C₃₉H₂₅N₃NaO₆ ⁺:654.1635；Found: 654.1633.

Example 2 naphthoquinone polyaSynthesis of Ring derivative 4b

47.4mg of 1, 4-naphthoquinone, 35.1mg of indole, 52mg of N-phenylmaleimide and 15.4mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added, the mixture reacts at 120 ℃ for 24 hours, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain a red solid 4b, wherein the yield is 54%.

Orange solid, melting point: 208-210 ℃.¹H NMR(400MHz,CDCl₃):δ9.22(d, J＝8.2Hz,1H),8.37–8.32(m,1H),8.29–8.24(m,1H),7.77–7.71(m, 2H),7.46(t,J＝7.7Hz,1H),7.23(dd,J＝6.8,4.4Hz,6H),7.01(d,J＝8.2Hz, 1H),6.95(t,J＝7.7Hz,1H),6.70(dd,J＝6.7,2.9Hz,4H),5.93(s,1H),4.14(d, J＝8.7Hz,2H),3.58(d,J＝8.7Hz,2H).13C NMR(101MHz,CDCl₃):δ 193.9,179.0,173.3,171.1,158.6,153.3,136.9,135.8,135.0,134.9,133.8, 130.6,130.1,129.2,129.1,128.3,126.7,126.1,120.7,120.2,118.1,111.6,69.7, 51.8,45.8,45.2.HRMS(ESI):m/z:[M+Na]⁺Calcd.for C₃₈H₂₃N₃NaO₆ ⁺: 640.1479；Found:640.1509.

EXAMPLE 3 Synthesis of naphthoquinone polycyclic derivative 4c

47.4mg of 1, 4-naphthoquinone, 62.2mg of N-benzylindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 4c, and the yield is 70%.

Red solid, melting point: 284-287 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.19 –9.16(d,1H),8.21–8.15(m,2H),7.87–7.80(m,4H),7.39–7.25 (m,10H),6.82–6.78(m,1H),6.66–6.58(m,4H),6.50(d,J＝8.4Hz, 1H),5.21(s,2H),4.39(d,J＝8.5Hz,2H),4.06(d,J＝8.5Hz,2H).¹³C NMR (101MHz,DMSO-d₆):δ193.8,178.8,174.5,172.4,160.0,154.3,137.4, 136.8,135.8,135.3,135.2,134.2,131.8,129.6,129.5,129.2,129.0,128.7, 127.8,127.7,126.8,126.7,120.8,118.2,116.7,110.0,74.1,52.0,49.3,46.2, 42.2.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₅H₃₀N₃O₆ ⁺:708.2135；Found: 708.2132.

Example 4 Synthesis of naphthoquinone polycyclic derivative 4d

47.4mg of 1, 4-naphthoquinone, 52mg of N-N-butylindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain a red solid 4d, wherein the yield is 80%.

Red solid, melting point: 260 ℃ and 263 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.15 (d,J＝7.4Hz,1H),8.24–8.11(m,2H),7.88–7.79(m,2H),7.47(ddd,J＝ 8.4,7.1,1.3Hz,1H),7.32–7.24(m,5H),6.87(d,J＝8.4Hz,1H),6.76(t,J＝ 7.4Hz,1H),6.62–6.59(m,3H),4.33(d,J＝8.5Hz,2H),4.01(d,J＝8.5Hz, 2H),3.86–3.75(m,2H),1.98(dt,J＝15.9,8.0Hz,2H),1.50(dq,J＝14.8, 7.4Hz,2H),0.99(t,J＝7.4Hz,3H).¹³C NMR(101MHz,DMSO-d₆):δ 194.1,178.5,174.5,172.0,159.4,154.1,137.2,136.0,135.3,135.1,134.0, 131.8,129.8,129.5,129.1,127.8,126.7,126.6,119.8,117.3,116.0,108.4,73.2, 51.9,46.0,44.3,42.1,30.5,20.8,14.5.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₂H₃₂N₃O₆ ⁺:674.2291；Found:674.2291.

EXAMPLE 5 Synthesis of naphthoquinone polycyclic derivative 4e

47.4mg of 1, 4-naphthoquinone, 49mg of N-allylindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain a red solid 4e, wherein the yield is 76%.

Red solid, melting point: 246248 deg.C.¹H NMR(400MHz,DMSO-d₆):δ9.15(d, J＝7.5Hz,1H),8.21–8.15(m,2H),7.87–7.82(m,2H),7.45(ddd,J＝ 8.5,7.2,1.3Hz,1H),7.33–7.23(m,6H),6.90(d,J＝8.4Hz,1H),6.81– 6.76(m,1H),6.66–6.58(m,4H),6.48-6.40(m,1H),5.61(dd,J＝17.4,1.4 Hz,1H),5.31(dd,J＝10.3,1.4Hz,1H),4.57(d,J＝6.4Hz,2H),4.31(d,J＝ 8.5Hz,2H),4.04(d,J＝8.5Hz,2H).¹³C NMR(101MHz,DMSO-d₆):δ 194.0,178.7,174.6,172.1,159.2,153.6,137.0,136.1,135.9,135.3,135.2, 134.2,131.7,129.7,129.5,129.1,127.8,126.7,126.6,120.0,118.2,117.6,116.5, 108.9,73.2,51.9,47.2,45.9,42.1.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₁H₂₈N₃O₆ ⁺:658.1978；Found:658.1981.

EXAMPLE 6 Synthesis of naphthoquinone polycyclic derivative 4f

47.4mg of 1, 4-naphthoquinone, 48mg of N-methyl-5-methoxyindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 12 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a blue solid 4f, and the yield is 92%.

Blue solid, melting point: 271 ℃ and 271 ℃.¹H NMR(400MHz,DMSO-d₆):δ8.76 (d,J＝2.7Hz,1H),8.21–8.15(m,2H),7.83(m,2H),7.33–7.20(m,7H), 6.88(d,J＝9.1Hz,1H),6.68–6.60(m,4H),4.26(d,J＝8.6Hz,2H),4.02(d, J＝8.6Hz,2H),3.77(s,3H),3.40(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ 194.2,178.2,174.7,172.0,155.2,153.7,150.9,136.1,135.3,135.1,133.9, 131.7,129.5,129.1,127.9,127.4,126.7,126.6,119.6,115.7,111.4,108.6,73.1, 56.2,51.9,45.8,41.8,28.7.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₀H₂₈N₃O₇ ⁺: 662.1927；Found:662.1926.

EXAMPLE 7 Synthesis of naphthoquinone polycyclic derivative 4g

47.4mg of 1, 4-naphthoquinone, 52mg of N-methyl-5-chloroindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain 4g of a red solid, and the yield is 87%.

Red solid, melting point: 298 ℃ and 302 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.22(d, J＝1.8Hz,1H),8.31–8.25(m,2H),7.98–7.92(m,2H),7.57(dd,J＝8.9, 1.7Hz,1H),7.37(dq,J＝14.4,7.2Hz,6H),7.04(d,J＝8.9Hz,1H),6.70(d,J ＝7.4Hz,4H),4.38(d,J＝8.5Hz,2H),3.50(s,3H).¹³C NMR(101MHz, DMSO-d₆):δ193.7,178.9,174.6,171.9,157.5,152.0,136.8,135.6,135.4, 135.3,134.5,131.6,129.6,129.2,128.1,127.9,126.7,126.6,120.4,120.1, 117.8,109.4,73.2,52.0,45.7,41.7,28.8.HRMS(ESI):m/z:[M+Na]⁺Calcd. for C₃₉H₂₄ClN₃NaO₆ ⁺:688.1246；Found:688.1284.

Example 8 naphthaleneSynthesis of quinopoly-cyclic derivative for 4h

47.4mg of 1, 4-naphthoquinone, 63mg of N-methyl-5-bromoindole, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of DCE are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid for 4 hours, and the yield is 83%.

Red solid, melting point: 288 ℃ and 291 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.30(d, J＝2.1Hz,1H),8.25–8.17(m,2H),7.90–7.85(m,2H),7.59(dd,J＝8.9, 2.2Hz,1H),7.36–7.25(m,6H),6.92(d,J＝8.9Hz,1H),6.68–6.60(m, 4H),4.31(d,J＝8.6Hz,2H),4.06(d,J＝8.5Hz,2H),3.42(s,3H).¹³C NMR (101MHz,DMSO-d₆):δ193.7,179.0,174.6,171.9,157.8,151.9,139.3, 135.6,135.4,135.3,134.5,131.6,131.1,129.6,129.2,128.0,126.7,126.6, 120.9,117.8,109.9,107.9,73.1,52.0,45.8,41.8,28.8.HRMS(ESI):m/z: [M+H]⁺Calcd.for C₃₉H₂₅BrN₃O₆ ⁺:710.0927；Found:710.0923.

Example 9 Synthesis of naphthoquinone polycyclic derivative 4i

47.4mg of 1, 4-naphthoquinone, 53mg of N-methyl-5-nitroindole, 52mg of N-phenylmaleimide, 15.4mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 30 hours at 120 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain an orange solid 4i, wherein the yield is 52%.

Orange solid, melting point: 297 to 300 ℃.¹H NMR(400MHz,DMSO-d₆):δ 10.07(d,J＝2.4Hz,1H),8.35(dd,J＝9.3,2.5Hz,1H),8.29–8.21(m,2H), 7.94–7.88(m,2H),7.33–7.24(m,6H),7.12(d,J＝9.4Hz,1H),6.68– 6.61(m,4H),4.42(d,J＝8.5Hz,2H),4.13(d,J＝8.5Hz,2H),3.55(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ193.1,179.5,174.5,171.9,161.3,150.7, 137.8,135.5,135.5,135.2,135.0,132.3,131.4,129.6,129.2,128.2,126.9, 126.6,126.2,120.4,118.6,107.9,74.2,52.1,46.0,41.8,29.5.HRMS(ESI):m/z: [M+H]⁺Calcd.for C₃₉H₂₅N₄O₈ ⁺:677.1672；Found:677.1667.

EXAMPLE 10 Synthesis of naphthoquinone polycyclic derivative 4j

47.4mg of 1, 4-naphthoquinone, 53mg of N-methyl-5-cyanoindole, 52mg of N-phenylmaleimide, 15.4mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 30 hours at 120 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out with dichloromethane, organic phases are combined, extraction is carried out with anhydrous magnesium sulfate, and column chromatography is carried out to obtain an orange solid 4j, wherein the yield is 55%.

Orange solid, melting point: 278 ℃ and 281 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.47 (d,J＝1.5Hz,1H),8.26–8.19(m,2H),7.90(dd,J＝5.8,3.3Hz,2H),7.83 (dd,J＝8.8,1.7Hz,1H),7.34–7.25(m,6H),7.10(d,J＝8.8Hz,1H),6.66 –6.60(m,4H),4.37(d,J＝8.5Hz,2H),4.10(d,J＝8.5Hz,2H),3.49(s,3H). ¹³C NMR(101MHz,DMSO-d₆):δ193.3,179.4,174.5,171.9,160.0,150.8, 139.4,135.5,135.3,134.8,134.0,131.5,129.6,129.3,128.1,126.9,126.6, 120.1,119.6,119.2,109.1,98.5,73.4,52.0,45.9,41.7,29.1.HRMS(ESI):m/z: [M+H]⁺Calcd.for C₄₀H₂₅N₄O₆ ⁺:657.1774；Found:657.1774.

EXAMPLE 11 Synthesis of naphthoquinone polycyclic derivative 4k

47.4mg of 1, 4-naphthoquinone, 60mg of N-methyl-5, 6-dichloroindole, 52mg of N-phenylmaleimide, 5.5mg of nickel trifluoromethanesulfonate and 3mL of acetonitrile are sequentially added into a reaction bottle, the mixture reacts at 120 ℃ for 30 hours, saturated saline solution is added after the mixture is cooled to room temperature, dichloromethane is used for extraction, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid 4k, and the yield is 70%.

Red solid, melting point: 306 ℃ and 308 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.31(s, 1H),8.24–8.19(m,2H),7.91–7.86(m,2H),7.36–7.26(m,7H),6.67 –6.63(m,4H),4.32(d,J＝8.5Hz,2H),4.07(d,J＝8.5Hz,2H),3.43(s,3H). ¹³C NMR(101MHz,DMSO-d₆):δ193.4,179.2,174.5,172.0,157.5,150.9, 139.7,135.4,135.4,134.7,131.5,129.7,129.6,129.2,128.0,126.8,126.6, 119.1,118.7,118.5,109.3,73.5,52.0,45.8,41.8,29.0.HRMS(ESI):m/z: [M+Na]⁺Calcd.for C₃₉H₂₃Cl₂N₃NaO₆ ⁺:722.0856；Found:722.0883.

EXAMPLE 12 Synthesis of naphthoquinone polycyclic derivative 4l

47.4mg of 1, 4-naphthoquinone, 49.5mg of N-methyl-6-methoxyindole, 52mg of N-phenylmaleimide, 7.8mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain 4l of an orange solid, and the yield is 76%.

Orange solid, melting point: 289-293 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.12 (d,J＝9.0Hz,1H),8.19–8.13(m,2H),7.85–7.77(m,2H),7.34–7.24 (m,6H),6.64(d,J＝7.2Hz,4H),6.40–6.33(m,2H),4.24(d,J＝8.6Hz, 2H),4.01(d,J＝8.6Hz,2H),3.84(s,3H),3.43(s,3H).¹³C NMR(101MHz, DMSO-d₆):δ194.6,177.7,174.7,172.2,167.7,161.7,152.6,136.4,135.2, 135.0,133.5,131.8,131.4,129.5,129.1,127.6,126.7,126.5,113.7,112.5, 107.5,90.4,73.6,56.2,51.5,46.5,41.9,28.7.HRMS(ESI):m/z:[M+H]⁺Calcd. for C₄₀H₂₈N₃O₇ ⁺:662.1927；Found:662.1926.

EXAMPLE 13 Synthesis of naphthoquinone polycyclic derivative 4m

47.4mg of 1, 4-naphthoquinone, 49mg of N-methyl-6-chloroindole, 52mg of N-phenylmaleimide, 7.8mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain an orange solid 4m, and the yield is 66%.

Orange solid, melting point: 313 ℃ and 316 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.13 (d,J＝8.7Hz,1H),8.21–8.16(m,2H),7.88–7.84(m,2H),7.34–7.25 (m,6H),7.05(d,J＝1.9Hz,1H),6.78(dd,J＝8.7,1.9Hz,1H),6.64–6.59 (m,4H),4.30(d,J＝8.5Hz,2H),4.06(d,J＝8.5Hz,2H),3.42(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ193.8,178.8,174.6,172.0,159.4,152.0, 142.3,135.7,135.4,135.3,134.3,131.6,131.0,129.6,129.2,127.8,126.7, 126.6,118.3,117.5,117.3,110.0,107.5,73.3,51.9,46.0,41.8,28.8.HRMS (ESI):m/z:[M+H]⁺Calcd.for C₃₉H₂₅ClN₃O₆ ⁺:666.1432；Found:666.1428.

EXAMPLE 14 Synthesis of naphthoquinone polycyclic derivative 4n

47.4mg of 1, 4-naphthoquinone, 45.8mg of N-methyl-6-fluoroindole, 52mg of N-phenylmaleimide, 7.8mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain an orange solid 4N, and the yield is 69%.

Orange solid, melting point: 285 ℃ 287 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.22 (dd,J＝9.0,6.2Hz,1H),8.20–8.15(m,2H),7.88–7.83(m,2H),7.33– 7.24(m,6H),6.81(dd,J＝10.6,2.3Hz,1H),6.64–6.60(m,4H),6.57(dd,J ＝9.1,2.3Hz,1H),4.28(d,J＝8.6Hz,2H),4.05(d,J＝8.5Hz,2H),3.41(s, 3H).¹³C NMR(101MHz,DMSO-d₆):δ193.9,178.6,174.6,172.0,δ 168.9(d,J＝253.3Hz),160.9(d,J＝14.7Hz),152.2,135.8,135.4,135.2,134.2, 132.3(d,J＝12.1Hz),131.7,129.5,129.2,127.8,126.6,116.4,116.1(d,J＝2.3 Hz),110.0,105.4(d,J＝23.9Hz),94.4(d,J＝26.3Hz),73.7,51.8,46.1,41.8, 28.9；¹⁹F NMR(376MHz,DMSO-d₆)δ-100.17.HRMS(ESI):m/z:[M+H]⁺ Calcd.for C₃₉H₂₅FN₃O₆ ⁺:650.1727；Found:650.1730.

EXAMPLE 15 Synthesis of naphthoquinone polycyclic derivative 4O

47.4mg of 1, 4-naphthoquinone, 60mg of N-methyl-7-methylindole, 52mg of N-phenylmaleimide, 7.8mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 16 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain a red solid 4o, wherein the yield is 93%.

Red solid, melting point: 276 ℃ and 278 ℃.¹H NMR(400MHz,CDCl₃):δ9.22(d,J ＝8.2Hz,1H),8.29(t,J＝8.6Hz,2H),7.75–7.67(m,2H),7.25–7.21(m, 6H),7.17(d,J＝7.1Hz,1H),6.75–6.67(m,5H),4.07(d,J＝8.8Hz,2H), 3.74(s,3H),3.63(d,J＝8.8Hz,2H),2.62(s,3H).¹³C NMR(101MHz,CDCl₃): δ194.2,178.4,173.4,170.6,157.5,152.8,140.5,136.4,134.9,134.8,133.4, 130.7,129.3,129.0,128.3,126.4,126.2,120.4,118.8,118.1,115.3,72.5,51.8, 45.3,42.0,31.8,20.4.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₀H₂₈N₃O₆ ⁺: 646.1973；Found:646.2003.

EXAMPLE 16 Synthesis of naphthoquinone polycyclic derivative 4p

63mg of 1, 4-anthraquinone, 39.3mg of N-methylindole, 52mg of N-phenylmaleimide, 7.8mg of tris (pentafluorophenyl) borane, 3mL of acetonitrile were added to the reaction flask in this order, the reaction was carried out at 100 ℃ for 24 reactions, the reaction flask was cooled to room temperature, saturated saline was added, extraction was carried out with dichloromethane, the organic phases were combined, extraction was carried out with anhydrous magnesium sulfate, and column chromatography was carried out to obtain 4p as a red solid with a yield of 70%.

Red solid, melting point: 289-292 deg.C.¹H NMR(400MHz,DMSO-d₆):δ9.21(d, J＝8.0Hz,1H),8.82(d,J＝9.2Hz,2H),8.30(dd,J＝6.1,3.4Hz,1H),8.21(dd, J＝6.1,3.4Hz,1H),7.74(dq,J＝6.8,3.5Hz,2H),7.50–7.45(m,1H),7.29 –7.19(m,6H),6.89(d,J＝8.4Hz,1H),6.76(t,J＝7.6Hz,1H),6.63– 6.58(m,4H),4.29(d,J＝8.5Hz,2H),4.10(d,J＝8.5Hz,2H),3.43(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ194.1,178.4,174.8,172.0,159.0,153.8, 137.2,135.3,134.7,132.0,131.7,131.6,130.4,130.1,130.1,129.9,129.9, 129.8,129.4,129.1,128.5,126.6,119.7,117.2,116.8,107.8,72.8,52.3,45.9, 41.8,28.6.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₃H₂₈N₃O₆ ⁺:682.1973； Found:682.2005.

EXAMPLE 17 Synthesis of naphthoquinone polycyclic derivative 4q

57mg of 5, 8-dihydroxy-1, 4-naphthoquinone, 39.3mg of N-methylindole, 52mg of N-phenylmaleimide, 7.8mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 30 hours at 120 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, and column chromatography is carried out to obtain a mauve solid 4q, wherein the yield is 77%.

Purple red solid, melting point: 211 ℃ and 213 ℃.¹H NMR(400MHz,DMSO-d₆):δ

13.48(s,1H),12.36(s,1H),9.06(d,J＝8.2Hz,1H),7.55(t,J＝7.7Hz,1H), 7.37–7.27(m,8H),6.99(d,J＝8.5Hz,1H),6.81(t,J＝7.6Hz,1H),6.70 –6.62(m,4H),4.37(d,J＝8.6Hz,2H),4.09(d,J＝8.6Hz,2H),3.47(s,3H). ¹³C NMR(101MHz,DMSO-d₆):δ200.2,183.0,174.3,171.8,159.8,156.9, 155.4,155.2,138.3,131.6,130.4,129.6,129.4,129.2,127.6,126.6,119.3, 117.9,116.2,115.2,114.3,108.4,73.2,51.7,45.8,41.5,28.7.HRMS(ESI):m/z: [M+H]⁺Calcd.for C₃₉H₂₆N₃O₈ ⁺:664.1714；Found:664.1744.

EXAMPLE 18 Synthesis of naphthoquinone polycyclic derivative 4r

95mg of 6, 7-dibromo-1, 4-naphthoquinone, 39.3mg of N-methylindole, 52mg of N-phenylmaleimide, 15.4mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid 4r, and the yield is 58%.

Red solid, melting point: 316-.¹H NMR(400MHz,CDCl₃):δ9.24(d,J ＝8.2Hz,1H),8.52(s,1H),8.51(s,1H),7.52(t,J＝7.6Hz,1H),7.25(d,J＝ 1.9Hz,4H),6.88–6.79(m,2H),6.74–6.67(m,4H),4.08(d,J＝8.8Hz, 2H),3.67(d,J＝8.8Hz,2H),3.47(s,3H).¹³C NMR(101MHz,CDCl₃):δ 192.6,176.5,173.4,170.3,159.1,153.2,138.0,135.4,134.1,133.7,133.1, 131.6,131.6,130.5,130.3,129.3,129.1,126.0,119.3,118.3,115.2,107.5,72.3, 51.9,45.4,42.1,28.3.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₃₉H₂₄Br₂N₃O₆ ⁺: 788.0032；Found:788.0029.

EXAMPLE 19 Synthesis of naphthoquinone polycyclic derivative 5a

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 30mg of maleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, and column chromatography is carried out to obtain a red solid 5a with the yield of 60%.

Red solid, melting point: 278 ℃ and 281 ℃.¹H NMR(400MHz,DMSO-d₆):δ11.10 (s,2H),9.07(d,J＝8.1Hz,1H),8.23–8.12(m,2H),7.88(dd,J＝9.1,5.6 Hz,2H),7.46(t,J＝7.6Hz,1H),6.88(d,J＝8.4Hz,1H),6.69(t,J＝7.6Hz, 1H),3.89(d,J＝8.6Hz,2H),3.75(d,J＝8.6Hz,2H),3.33(s,3H).¹³C NMR (101MHz,DMSO-d₆):δ194.3,178.6,176.9,174.3,158.9,153.6,136.8, 136.2,135.4,134.9,134.0,130.1,127.7,126.6,119.5,116.6,107.7,72.2,51.2, 47.1,42.9,28.5.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₂₇H₁₈N₃O₆ ⁺:480.1190； Found:480.1212.

EXAMPLE 20 Synthesis of naphthoquinone polycyclic derivative 5b

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 34mg of N-methylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 5b, and the yield is 67%.

Red solid, melting point: 273 and 275 ℃.¹H NMR(400MHz,DMSO-d₆):δ8.98(d, J＝8.1Hz,1H),8.22–8.14(m,2H),7.91–7.85(m,2H),7.48–7.43(m, 1H),6.88(d,J＝8.4Hz,1H),6.67(t,J＝7.6Hz,1H),4.02(d,J＝8.6Hz,2H), 3.80(d,J＝8.6Hz,2H),3.38(s,3H),2.38(s,6H).¹³C NMR(101MHz, DMSO-d₆):δ194.1,178.3,175.4,172.9,158.8,153.3,137.0,136.1,135.2, 135.1,134.0,130.0,127.8,126.7,119.3,116.8,116.2,107.6,72.2,51.3,45.8, 41.7,28.5,24.8.HRMS(ESI):m/z:[M+Na]⁺Calcd.for C₂₉H₂₁N₃NaO₆ ⁺: 530.1323；Found:530.1350.

EXAMPLE 21 Synthesis of naphthoquinone polycyclic derivative 5c

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 42mg of N-N-propylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 5c, and the yield is 67%.

Red solid, melting point: 291-293 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.00(d, J＝7.9Hz,1H),8.23–8.15(m,2H),7.91–7.86(m,2H),7.48–7.43(m, 1H),6.88(d,J＝8.4Hz,1H),6.67(t,J＝7.3Hz,1H),4.00(d,J＝8.5Hz,2H), 3.81(d,J＝8.5Hz,2H),3.39(s,3H),2.91(t,J＝6.9Hz,4H),0.89–0.81(m, 4H),0.32(t,J＝7.5Hz,6H).¹³C NMR(101MHz,DMSO-d₆):δ194.2,178.2, 175.4,172.8,158.8,153.3,136.9,136.2,135.3,135.1,133.9,130.0,127.6, 126.6,119.7,116.7,116.3,107.5,72.3,51.5,45.6,41.6,39.8,28.5,20.4,10.9. HRMS(ESI):m/z:[M+H]⁺Calcd.for C₃₃H₃₀N₃O₆ ⁺:564.2135；Found: 564.2132.

EXAMPLE 22 Synthesis of naphthoquinone polycyclic derivative 5d

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 54mg of N-cyclohexylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 5d, and the yield is 72%.

Red solid, melting point: 296 ℃ and 300 ℃.¹H NMR(400MHz,DMSO-d₆):δ8.97(d, J＝8.0Hz,1H),8.17(td,J＝4.4,2.4Hz,2H),7.90–7.84(m,2H),7.47– 7.42(m,1H),6.86(d,J＝8.4Hz,1H),6.66(t,J＝7.6Hz,1H),3.90(d,J＝8.5 Hz,2H),3.75(d,J＝8.5Hz,2H),3.35(s,3H),1.53–1.26(m,11H),1.02– 0.73(m,11H).¹³C NMR(101MHz,DMSO-d₆):δ194.4,178.3,175.4,172.6, 158.8,153.0,136.9,136.0,135.5,135.0,133.9,129.7,127.7,126.5,119.7, 116.7,116.2,107.5,72.4,51.7,50.9,45.3,41.1,28.4,28.1,27.9,25.4,24.9. HRMS(ESI):m/z:[M+H]⁺Calcd.for C₃₉H₃₈N₃O₆ ⁺:644.2761；Found: 644.2758.

EXAMPLE 23 Synthesis of naphthoquinone polycyclic derivative 5e

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 61mg of N- (4-methoxy) phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 5e, and the yield is 57%.

Red solid, melting point: 220 ℃ and 222 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.13(d, J＝7.9Hz,1H),8.18(ddd,J＝4.9,2.3,0.9Hz,2H),7.87–7.82(m,2H),7.47 (ddd,J＝8.4,7.1,1.3Hz,1H),6.88(d,J＝8.4Hz,1H),6.86–6.80(m,4H), 6.76–6.72(m,1H),6.54–6.47(m,4H),4.23(d,J＝8.5Hz,2H),4.01(d, J＝8.5Hz,2H),3.63(s,6H),3.41(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ 194.2,178.5,174.9,172.2,159.5,159.0,153.5,137.2,136.0,135.4,135.1, 134.0,129.7,127.8,127.8,126.6,124.2,119.5,117.1,116.4,114.8,107.8,72.7, 55.8,51.9,45.8,41.7,28.6.HRMS(ESI):m/z:[M+Na]⁺Calcd.for C₄₁H₂₉N₃NaO₈ ⁺:714.1847；Found:714.1881.

EXAMPLE 24 Synthesis of naphthoquinone polycyclic derivative 5f

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 66mg of N- (4-methylthio) phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 5f, and the yield is 51%.

Red solid, melting point: 241 ℃ and 244 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.12(d, J＝8.1Hz,1H),8.18(dd,J＝5.5,2.6Hz,2H),7.85(p,J＝7.2Hz,2H),7.48(t, J＝7.6Hz,1H),7.17(d,J＝8.6Hz,4H),6.89(d,J＝8.4Hz,1H),6.74(t,J＝ 7.6Hz,1H),6.53(d,J＝8.6Hz,4H),4.26(d,J＝8.5Hz,2H),4.02(d,J＝8.5 Hz,2H),3.41(s,3H),2.36(s,6H).¹³C NMR(101MHz,DMSO-d₆):δ194.1, 178.5,174.7,172.0,159.0,153.5,139.8,137.3,136.0,135.3,135.1,134.1, 129.7,128.2,127.8,127.0,126.6,126.5,119.4,117.2,116.3,107.8,72.7,51.9, 45.9,41.7,28.6,14.9.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₁H₃₀N₃O₆S₂ ⁺: 724.1576；Found:724.1575.

EXAMPLE 25 Synthesis of naphthoquinone polycyclic derivative 5g

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 76mg of N- (4-bromo) phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain 5g of red solid, and the yield is 80%.

Red solid, melting point: 233-.¹H NMR(400MHz,DMSO-d₆):δ9.10(d, J＝8.1Hz,1H),8.22–8.14(m,2H),7.89–7.83(m,2H),7.59–7.50(m, 4H),7.50–7.45(m,1H),6.90(d,J＝8.4Hz,1H),6.74(t,J＝7.6Hz,1H), 6.62–6.52(m,4H),4.29(d,J＝8.6Hz,2H),4.03(d,J＝8.6Hz,2H),3.41(s, 3H).¹³C NMR(101MHz,DMSO-d₆):δ194.0,178.5,174.4,171.7,159.0, 153.4,137.4,135.9,135.3,135.2,134.1,132.6,130.9,129.7,128.6,127.8, 126.6,122.2,119.3,117.3,116.3,107.8,72.6,51.8,46.0,41.8,28.6.HRMS (ESI):m/z:[M+H]⁺Calcd.for C₃₉H₂₄Br₂N₃O₆ ⁺:790.0006；Found:790.0038.

EXAMPLE 26 Synthesis of naphthoquinone polycyclic derivative 5h

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 60mg of N- (4-cyano) phenyl maleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid for 5 hours, and the yield is 72%.

Red solid, melting point: 260 ℃ and 263 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.10(d, J＝8.1Hz,1H),8.20(ddd,J＝6.7,3.6,1.5Hz,2H),7.89(m,7.92-7.87Hz,2H), 7.83(d,J＝8.5Hz,4H),7.51(t,J＝7.7Hz,1H),6.93(d,J＝8.4Hz,1H),6.84 (d,J＝8.5Hz,4H),6.76(t,J＝7.6Hz,1H),4.36(d,J＝8.6Hz,2H),4.08(d,J＝ 8.6Hz,2H),3.44(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ193.9,178.4, 174.2,171.5,159.0,153.4,137.5,135.9,135.5,135.3,135.2,134.2,133.8, 129.7,127.9,127.3,126.7,119.2,118.4,117.4,116.2,111.8,107.9,72.6,51.8, 46.0,41.8,28.6.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₁H₂₄N₅O₆ ⁺:682.1727； Found:682.1726.

EXAMPLE 27 Synthesis of naphthoquinone polycyclic derivative 5i

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 70mg of N- (4-carbomethoxy) phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, and column chromatography is carried out to obtain 5i of a red solid, wherein the yield is 69%.

Red solid, melting point: 252 ℃ and 256 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.12(d, J＝8.1Hz,1H),8.22–8.18(m,2H),7.93–7.85(m,6H),7.50(ddd,J＝ 8.3,7.1,1.3Hz,1H),6.92(d,J＝8.4Hz,1H),6.85–6.79(m,4H),6.76(dd,J ＝11.3,4.0Hz,1H),4.35(d,J＝8.6Hz,2H),4.08(d,J＝8.6Hz,2H),3.79(s, 6H),3.45(s,3H).¹³C NMR(101MHz,DMSO-d₆):δ194.0,178.4,174.3, 171.7,165.7,159.0,153.5,137.4,135.9,135.7,135.3,134.2,130.4,130.0, 129.8,127.9,126.8,126.6,119.3,117.3,116.3,107.9,72.7,52.8,51.8,46.1, 41.9,28.6.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₃H₃₀N₃O₁₀ ⁺:748.1931； Found:748.1929.

EXAMPLE 28 Synthesis of naphthoquinone polycyclic derivative 5j

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 57mg of N- (2-methyl) phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain 5j of a red solid, and the yield is 68%.

Red solid, melting point: 287-289 ℃.¹H NMR(400MHz,CDCl₃):δ9.48– 9.16(m,1H),8.33(dd,J＝14.1,7.7Hz,2H),7.85–7.76(m,1H),7.75– 7.67(m,1H),7.47(t,J＝7.7Hz,1H),7.22–6.98(m,6H),6.94–6.24(m, 4H),4.20–4.06(m,2H),3.69–3.57(m,2H),3.34–3.20(m,3H),2.09 –1.43(m,6H).¹³C NMR(101MHz,CDCl₃):δ194.6,194.6,178.6,178.6, 174.1,173.8,170.7,170.6,158.7,153.2,137.4,137.3,136.4,136.3,136.1, 136.0,135.1,135.0,135.0,133.6,131.2,131.0,130.8,130.6,130.1,130.1, 129.9,129.7,128.3,127.5,127.4,127.3,126.8,126.8,126.3,120.0,119.7, 117.9,117.8,116.5,116.3,107.2,107.2,77.3,77.0,76.7,72.1,71.9,51.8,51.7, 45.8,45.6,45.5,42.6,42.5,42.5,28.2,28.1,28.1,17.4,17.2,17.2.HRMS(ESI): m/z:[M+H]⁺Calcd.for C₄₁H₃₀N₃O₆ ⁺:660.2135；Found:660.2134.

EXAMPLE 29 Synthesis of naphthoquinone polycyclic derivative 5k

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 72mg of N-2- (3-carbomethoxy) thienylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain 5k of a red solid, and the yield is 54%.

Red solid, melting point: 208 ℃ and 219 ℃.¹H NMR(400MHz,CDCl₃):δ9.27(d,J ＝8.1Hz,1H),8.36–8.31(m,1H),8.31–8.26(m,1H),7.76–7.69(m, 2H),7.46(t,J＝7.5Hz,1H),7.33(d,J＝5.3Hz,2H),6.84–6.75(m,2H), 6.35(d,J＝5.0Hz,2H),4.16(d,J＝8.9Hz,2H),3.76(d,J＝8.9Hz,2H),3.68 (s,6H),3.44(s,3H).¹³C NMR(101MHz,CDCl₃):δ193.5,178.9,172.2, 169.7,160.0,158.6,152.2,137.1,136.3,134.9,134.6,133.4,132.5,130.5, 130.5,128.0,127.0,126.8,126.7,117.8,116.8,107.1,72.0,52.2,51.6,45.7, 42.6,28.3.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₃₉H₂₆N₃O₁₀S₂ ⁺:760.1060； Found:760.1063.

EXAMPLE 30 Synthesis of naphthoquinone polycyclic derivative 5l

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 66mg of ethylenebismaleimide and 7.7mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added, the reaction is carried out for 24 hours at 100 ℃, saturated saline is added after the reaction is cooled to room temperature, the extraction is carried out by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, and column chromatography is carried out to obtain 5l of red solid with the yield of 51%.

Red solid, melting point: 283 ℃ 287 ℃.¹H NMR(400MHz,DMSO-d₆):δ8.96(d, J＝7.9Hz,1H),8.20–8.14(m,2H),7.91–7.86(m,2H),7.47–7.42(m, 1H),6.87(d,J＝10.5Hz,5H),6.67(t,J＝7.4Hz,1H),4.03(d,J＝8.7Hz,2H), 3.73(d,J＝8.7Hz,2H),3.35(s,3H),3.15–3.05(m,8H).¹³C NMR(101 MHz,DMSO-d₆):δ193.8,178.1,175.0,172.5,171.0,158.7,152.9,137.0, 136.2,135.2,135.0,134.9,134.0,130.3,127.9,126.6,119.3,117.0,115.9,107.6, 71.9,51.1,45.5,41.4,36.9,34.5,28.5.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₃₉H₂₈N₅O₁₀ ⁺:726.1836；Found:726.1830.

EXAMPLE 31 Synthesis of naphthoquinone polycyclic derivative 5m

47.4mg of 1, 4-naphthoquinone, 39.3mg of N-methylindole, 81mg of N-triethylene diglycol monomethyl ester maleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, then extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain a red solid 5m, and the yield is 44%.

Red solid, melting point: 200 ℃ and 202 ℃.¹H NMR(400MHz,CDCl₃):δ9.16(d,J ＝8.1Hz,1H),8.39–8.34(m,1H),8.30–8.26(m,1H),7.79(p,J＝5.7Hz, 2H),7.47(t,J＝7.7Hz,1H),6.76(dd,J＝14.5,7.7Hz,2H),3.87(d,J＝8.7Hz, 2H),3.53–3.45(m,10H),3.43(s,3H),3.40–3.32(m,10H),3.32– 3.23(m,8H),3.12(t,J＝5.6Hz,4H).¹³C NMR(101MHz,CDCl₃):δ193.8, 178.4,173.8,171.3,158.5,152.1,136.9,136.1,135.0,134.6,133.5,130.5, 127.9,126.7,119.6,117.4,116.2,106.8,71.8,71.7,70.3,69.9,66.5,59.0,51.3, 45.2,42.1,38.3,28.2.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₁H₄₆N₃O₁₂ ⁺: 772.3081；Found:772.3080.

Example 32 Synthesis of naphthoquinone polycyclic derivative 5n

The reaction flask is sequentially added with 1mg, 4-naphthoquinone, 80mg of N-methylindole, 54mg of N-cyclohexylmaleimide, 30mg of maleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile, the mixture reacts for 24h at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain 5N red solid, wherein the yield is 37%.

Red solid, melting point: 212 ℃ and 217 ℃.¹H NMR(400MHz,DMSO-d₆):δ11.14 (s,1H),9.07(d,J＝7.9Hz,1H),8.25–8.18(m,2H),7.95–7.89(m,2H), 7.52–7.47(m,1H),6.91(d,J＝8.4Hz,1H),6.72(t,J＝7.4Hz,1H),3.94 (dd,J＝15.9,8.5Hz,2H),3.79(dd,J＝8.5,3.7Hz,2H),3.38(s,3H),1.55– 1.37(m,5H),1.11–0.75(m,6H).¹³C NMR(101MHz,DMSO-d₆):δ 194.3,178.5,176.8,175.4,174.3,172.7,158.9,153.3,136.9,136.1,135.4, 134.9,133.9,129.8,127.7,126.5,119.6,116.7,116.4,107.6,72.3,51.4,50.9, 46.8,45.6,42.7,41.3,28.5,28.0,27.9,25.4,24.9.HRMS(ESI):m/z:[M+H]⁺ Calcd.for C₃₃H₂₈N₃O₆ ⁺:562.1978；Found:562.1976.

EXAMPLE 33 Synthesis of naphthoquinone polycyclic derivative 5O

95mg of 1, 4-naphthoquinone, 80mg of N-methylindole, 54mg of N-cyclohexylmaleimide, 52mg of N-phenylmaleimide, 7.7mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline solution is added after the mixture is cooled to room temperature, dichloromethane is used for extraction, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid 5o, and the yield is 30%.

Red solid, melting point: 294 and 296 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.07(d, J＝8.1Hz,1H),8.23–8.16(m,2H),7.91–7.84(m,2H),7.48(ddd,J＝ 8.3,7.1,1.2Hz,1H),7.32–7.22(m,3H),6.89(d,J＝8.4Hz,1H),6.72(dd,J ＝11.3,4.0Hz,1H),6.62–6.55(m,2H),4.18(d,J＝8.5Hz,1H),4.03(d,J＝ 8.5Hz,1H),3.97(d,J＝8.5Hz,1H),3.86(d,J＝8.4Hz,1H),3.40(s,3H),1.53 –1.36(m,5H),1.08–0.71(m,6H).¹³C NMR(101MHz,DMSO-d₆):δ 194.2,178.4,175.4,174.7,172.7,172.0,158.9,153.3,137.1,136.0,135.4, 135.1,134.0,131.7,129.7,129.4,129.1,127.8,126.6,126.5,119.6,117.0,116.3, 107.7,72.6,51.8,50.9,45.9,45.3,41.8,41.1,28.5,28.1,27.9,25.4,24.9. HRMS(ESI):m/z:[M+H]⁺Calcd.for C₃₉H₃₂N₃O₆ ⁺:638.2291.

EXAMPLE 34 Synthesis of naphthoquinone polycyclic derivative 5p

47.4mg of 1, 4-naphthoquinone, 47mg of N-methyl-5-cyanoindole, 66mg of ethylenebismaleimide and 15.4mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added into the reaction flask, the reaction is carried out for 30h at 120 ℃, saturated saline is added after the reaction is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain an orange solid 5p, wherein the yield is 47%.

Orange solid, melting point: 276 ℃ and 278 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.33 (d,J＝1.6Hz,1H),8.23–8.17(m,2H),7.94–7.90(m,2H),7.79(dd,J＝ 8.8,1.7Hz,1H),7.06(d,J＝8.8Hz,1H),6.78(s,4H),4.07(d,J＝8.7Hz,2H), 3.78(d,J＝8.7Hz,2H),3.41(s,3H),3.11(s,8H).¹³C NMR(101MHz, DMSO-d₆):δ193.1,178.8,174.9,172.5,170.9,159.7,150.1,139.0,135.6, 135.4,135.0,134.8,134.7,128.2,126.8,120.3,119.2,119.1,108.7,98.1,72.5, 51.3,45.5,41.4,37.1,34.7,28.9.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₀H₂₇N₆O₁₀ ⁺:751.1789；Found:751.1788.

EXAMPLE 35 Synthesis of naphthoquinone polycyclic derivative 5q

47.4mg of 1, 4-naphthoquinone, 47mg of N-methyl-6-cyanoindole, 66mg of ethylenebismaleimide, 15.4mg of tris (pentafluorophenyl) borane and 3mL of acetonitrile are sequentially added into a reaction flask, the mixture is reacted for 24 hours at 100 ℃, saturated saline is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain an orange solid of 5q, wherein the yield is 50%.

Orange solid, melting point: 285 ℃ and 288 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.06 (d,J＝8.2Hz,1H),8.19(d,J＝21.0Hz,2H),7.98–7.89(m,2H),7.44(s, 1H),7.05(d,J＝8.2Hz,1H),6.84(s,4H),4.09(d,J＝8.5Hz,2H),3.79(d,J＝ 8.7Hz,2H),3.40(s,3H),3.12(s,8H).¹³C NMR(101MHz,DMSO-d₆):δ 193.1,178.7,174.9,172.5,170.9,157.2,150.6,135.7,135.4,135.0,134.8, 134.6,131.1,128.1,126.8,122.5,120.2,119.7,119.2,117.3,110.7,110.0,72.2, 51.5,45.2,41.4,37.0,34.6,28.7.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₀H₂₇N₆O₁₀ ⁺:751.1789；Found:751.1783.

EXAMPLE 36 Synthesis of naphthoquinone polycyclic derivative 5r

47.4mg of 1, 4-naphthoquinone, 47mg of N-methyl-7-cyanoindole, 66mg of ethylenebismaleimide and 15.4mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added into the reaction flask, the reaction is carried out for 30h at 120 ℃, saturated saline is added after the reaction is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, and column chromatography is carried out to obtain an orange solid 5r, wherein the yield is 52%.

Orange solid, melting point: 287-290 ℃.¹H NMR(400MHz,DMSO-d₆):δ9.31 (d,J＝7.9Hz,1H),8.24–8.16(m,2H),7.94(s,2H),7.83(d,J＝7.5Hz,1H), 6.90–6.78(m,5H),4.12(d,J＝8.5Hz,2H),3.79(d,J＝8.5Hz,2H),3.70(s, 3H),3.14(s,8H).¹³C NMR(101MHz,DMSO-d₆):δ193.0,178.8,174.9, 172.6,170.9,156.3,149.5,141.5,135.7,135.6,135.4,134.9,134.8,134.7, 128.2,126.8,121.8,119.6,118.6,117.7,89.5,72.7,51.4,45.4,41.2,37.1,34.6, 30.2.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₀H₂₇N₆O₁₀ ⁺:751.1789；Found: 751.1777.

EXAMPLE 37 Synthesis of naphthoquinone polycyclic derivative 5s

95mg of 6, 7-dibromo-1, 4-naphthoquinone, 47mg of N-methyl-6-cyanoindole, 66mg of ethylenebismaleimide and 15.4mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added, the mixture reacts at 120 ℃ for 30 hours, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, column chromatography is carried out to obtain a red solid for 5s, and the yield is 38%.

Red solid, melting point: 294-.¹H NMR(400MHz,CDCl₃):δ9.08(d,J ＝7.8Hz,1H),8.52(s,1H),8.49(s,1H),7.48(t,J＝7.7Hz,1H),6.79–6.73 (m,2H),6.56(d,J＝7.7Hz,4H),3.80(d,J＝8.9Hz,2H),3.52–3.47(m, 6H),3.42(s,3H),3.33(ddd,J＝14.6,7.9,3.9Hz,4H).¹³C NMR(101MHz, CDCl₃):δ175.9,174.1,173.0,171.3,170.5,170.4,137.7,135.5,134.1,134.0, 133.5,131.8,130.8,130.2,123.7,119.4,117.9,116.1,107.0,105.4,77.3,77.2, 77.0,76.7,45.5,43.7,42.0,40.9,40.3,38.2,37.6,35.6,35.1,28.3.HRMS(ESI): m/z:[M+H]⁺Calcd.for C₃₉H₂₆N₆O₁₀Br₂ ⁺:882.0046；Found:882.0036.

EXAMPLE 38 Synthesis of naphthoquinone polycyclic derivative 5t

56mg of 5, 8-dimethyl-1, 4-naphthoquinone, 47mg of N-methyl-6-cyanoindole, 66mg of ethylenebismaleimide and 15.4mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added, the mixture reacts at 120 ℃ for 30 hours, saturated saline solution is added after the mixture is cooled to room temperature, the mixture is extracted by dichloromethane, organic phases are combined, anhydrous magnesium sulfate is used for extraction, and column chromatography is carried out to obtain 5t of red solid with the yield of 46%.

Orange solid, melting point: 254 ℃ and 258 ℃.¹H NMR(400MHz,CDCl₃):δ8.83(d, J＝8.0Hz,1H),7.43(s,3H),6.75(dd,J＝16.3,8.0Hz,2H),6.54(s,4H),3.78 (d,J＝8.7Hz,2H),3.46(s,2H),3.44(s,4H),3.39(s,3H),3.35(s,2H),3.25(d, J＝13.2Hz,2H),2.84(s,3H),2.77(s,3H).¹³C NMR(101MHz,CDCl₃):δ 194.9,182.4,173.9,171.7,170.4,157.7,148.9,139.7,139.5,137.8,136.4, 136.0,135.6,134.9,134.0,130.1,119.0,117.8,117.3,106.6,71.0,51.4,44.9, 42.5,38.0,35.1,29.7,28.1,27.1,23.7,23.6.HRMS(ESI):m/z:[M+H]⁺Calcd. for C₄₁H₃₂N₅O₁₀ ⁺:754.2149；Found:754.2148.

Example 39 Synthesis of naphthoquinone polycyclic derivative 5u

47.4mg of 1, 4-naphthoquinone, 53mg of N-methyl-5-carboxyindole, 65mg of N- (2-nitro) -phenylmaleimide and 15.4mg of tris (pentafluorophenyl) borane are sequentially added into a reaction flask, 3mL of acetonitrile is added, the mixture is reacted at 120 ℃ for 24 hours, a saturated saline solution is added after the mixture is cooled to room temperature, extraction is carried out by using dichloromethane, organic phases are combined, extraction is carried out by using anhydrous magnesium sulfate, column chromatography is carried out to obtain 5u of a red solid, and the yield is 49%.

Red solid, melting point: 276 ℃ and 278 ℃.¹H NMR(400MHz,DMSO-d₆):δ13.12 (s,1H),9.39-9.17(m,1H),9.20(d,J＝8.4Hz,1H),8.28–8.05(m,3H),7.94 –7.70(m,5H),7.68–7.53(m,2H),7.41–6.33(m,4H),4.40–4.24 (m,2H),4.02(d,J＝26.5Hz,2H),3.47-3.2(m,3H).¹³C NMR(101MHz, DMSO-d₆):δ193.5,193.5,185.3,185.3,180.5,180.4,173.8,173.7,171.6, 171.6,159.7,154.2,138.3,137.5,137.4,136.8,136.1,136.0,135.8,135.5, 135.1,134.4,133.2,131.3,131.3,130.9,130.5,130.4,133.1,129.9,128.8, 128.0,127.9,127.8,127.1,127.0,126.6,121.0,120.,118.4,118.0,117.5,117.3, 109.2,109.2,72.6,72.5,51.8,51.7,45.4,45.3,45.3,41.8,41.5,41.4,30.6,30.6, 30.4.HRMS(ESI):m/z:[M+H]⁺Calcd.for C₄₀H₂₄N₅O₁₂ ⁺:766.1421；Found: 766.1421.

The photophysical properties of the synthesized compounds 4a-4r, 5a-5o are shown in Table 1.

Table 1: photophysical characterization data for Compounds No. 4a-4r, 5a-5o

As can be seen from Table 1, some target compounds have excellent fluorescence properties and have application prospects in being chemoreceptors and fluorescent materials.

The anti-tumor cell activity test of partial compounds in 4a-4r, 5a-5o is carried out by in vitro cell experiments, and the results are shown in Table 2.

TABLE 2 IC of 6 Compounds on 4 tumor cells₅₀Value (x ± s, N ═ 3)

As shown in Table 2, compounds 4k and 5l have certain antitumor activity, so that the structure of the compound is modified to synthesize compounds 5p-5u, and the antitumor activity of 5p-5u is tested, and the data is shown in Table 3.

Table 3: test results of antitumor Activity of Compound 5p-5u

It can be seen from table 3 that compounds 5s and 5t exhibit certain biological activities against mouse melanoma cells and human colon cancer cells, and can be used as candidate drug molecules against cancer and tumors.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

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Naphthoquinone polycyclic derivative, preparation method and application thereof

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