Green synthesis method and weeding application of indole fused and mixed tetracyclic skeleton

Abstract

The invention discloses an indole fused and mixed tetracyclic skeleton as well as a synthesis method and application thereof. The invention provides an indole fused and mixed tetracyclic skeleton structure. The synthetic method comprises the following steps: uniformly mixing N-aryl methylindole and o-alkoxy substituted benzaldehyde in a solvent, and reacting at the temperature of 100-120 DEG C under an acidic condition, so as to prepare the indole fused and mixed tetracyclic compound. The invention also provides an application of the indole fused and mixed tetracyclic skeleton in preparation of herbicides. According to the method for green synthesis of the indole fused and mixed tetracyclic compound provided by the invention, N-aryl methylindole and o-alkoxy substituted benzaldehyde are subjected to a hydrogen migration cyclization reaction based on a'shearing-sewing 'strategy to realize efficient construction of an indole fused and mixed tetracyclic skeleton.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical intermediates and chemical synthesis, and in particular to an indole fused tetracyclic structure and a synthesis method and application thereof. Background Art

[0002] Indole fused tetracyclic structures are widely present in many natural products and drug molecules, and have important application value in medicine and pesticides. For example, the natural product (-)-goniomitine has an indole fused tetracyclic structure, which shows very good anti-inflammatory activity. However, there is currently a lack of efficient synthetic methods for constructing indole fused tetracyclics, which seriously hinders the subsequent biological activity research of indole fused tetracyclic molecules. Therefore, the efficient construction of indole fused tetracyclics is of great significance for drug development.

[0003]

[0004] For example, in 2014, John P. Wolfe's research group at Michigan State University achieved a transition metal palladium-catalyzed intramolecular olefin amine arylation reaction and efficiently synthesized indoline-type fused tetracyclic molecules in one step (J. Org. Chem. 2014, 79, 4212−4217).

[0005]

[0006] Indole fused tetracyclic structures have significant biological activity. The above-mentioned reported methods can synthesize indoline fused tetracyclic structures, but an efficient synthesis method of indole fused tetracyclic structures has not been reported. Therefore, developing an efficient and direct method for synthesizing indole fused tetracyclic compounds is of great significance for the development of new herbicides and drugs, especially drugs for treating tumors, pain, depression and other diseases. Summary of the invention

[0007] The purpose of the present invention is to provide a biologically active indole-type fused tetracyclic structure and its synthesis method and application in view of the deficiencies in the prior art. The indole-type fused tetracyclic skeleton provided by the present invention will provide a new model molecule for drug development. The synthesis method of the indole-type fused tetracyclic skeleton provided by the present invention is to efficiently synthesize the skeleton in one step by reacting N-arylmethyl indole with o-alkoxy substituted benzaldehyde through a hydrogen migration cyclization reaction based on the "cut-stitch" strategy for the first time. The operation is simple, efficient and practical, and the constructed skeleton contains a variety of functional groups, which is beneficial to the later synthesis and application of the skeleton. The technical solution of the present invention is achieved in this way: Indole fused tetracyclic skeleton, the structural formula of which is shown in Formula 1:

[0008] In formula 1, R 1 is any one of a methoxy group and a benzene ring; R 2 is any one of methoxy, fluorine, chlorine, bromine and methyl; R 3 is any one of tert-butyl and methyl; R 4 is any one of substituted benzene, naphthalene ring, and methyl; wherein R 1 , R 2 , R 3 , R 4 They are the same as or different from each other and each independently represents a substituent.

[0009] The compounds involved in the present invention may exist in the form of one or more stereoisomers. Various isomers include tautomers, geometric isomers, enantiomers, diastereomers, etc. These isomers and mixtures of these isomers are all within the protection scope of the present invention.

[0010] Based on the same inventive concept, the present invention also provides a method for synthesizing an indole fused tetracyclic skeleton. The synthetic process route of the present invention is as follows: Figure 1 As shown, the following steps are included: The N-arylmethyl indole and the o-alkoxy substituted benzaldehyde are uniformly mixed in a solvent, and reacted at 100-120° C. under acidic conditions to obtain an indole-type fused tetracyclic compound; Wherein, the structural formula of the above-mentioned N-arylmethyl indole is shown in Formula 2:

[0011] In formula 2, R 1 is any one of a methoxy group and a benzene ring; R 2 Any one of methoxy, fluorine, chlorine, bromine and methyl; Wherein, the structural formula of the above-mentioned o-alkoxy substituted benzaldehyde is shown in Formula 3:

[0012] In formula 3, R 3 is any one of tert-butyl and methyl; R 4 It is any one of substituted benzene, naphthalene ring and methyl group. The reaction conditions can be detected by thin layer chromatography, and purification is performed after the reaction is completed to obtain a purified product of the indole fused tetracyclic compound. The above reaction process is specifically as follows: Two molecules of N-arylmethyl indole react with o-alkoxy-substituted benzaldehyde under acidic conditions to generate triarylmethane intermediate 7a, which then undergoes reverse Friedel-Crafts alkylation to generate intermediate I, followed by 1,5-negative hydrogen migration to generate intermediate II, which then undergoes cyclization to generate indole-oxygenated seven-membered ring skeleton intermediate III, and intermediate III undergoes intramolecular nucleophilic substitution to generate indole-type fused tetracyclic compounds. The specific synthesis principle route is as follows:

[0013] Preferably, the synthesis method as described above is carried out at 120°C.

[0014] In the above-mentioned synthesis method, the molar ratio of the N-arylmethyl indole to the o-alkoxy substituted benzaldehyde is (1-2): 1. Preferably, the molar ratio of the N-arylmethyl indole to the o-alkoxy substituted benzaldehyde is 1.2:1.

[0015] In the above-mentioned synthesis method, the solvent is ethylene dichloride, toluene, dimethyl carbonate or ethyl acetate.

[0016] In the above-mentioned synthesis method, the amount of the solvent is: 10 to 25 L of solvent is added per mole of N-arylmethyl indole and o-alkoxy substituted benzaldehyde. Preferably, the amount of the solvent is: 10 L of solvent is added per mole of N-arylmethyl indole and o-alkoxy substituted benzaldehyde.

[0017] In the above-mentioned synthesis method, the acidic catalyst is added before the reaction, and the catalyst is a Lewis acid. Preferably, the catalyst is any one of boron trifluoride etherate, p-toluenesulfonic acid, camphorsulfonic acid, and copper trifluoromethanesulfonate.

[0018] In the above-mentioned synthesis method, the amount of the acidic catalyst is 20-100 mol%. Preferably, the amount of the catalyst is 30 mol%.

[0019] Based on the same inventive concept, the present invention also provides a pharmaceutical composition, which comprises the indole fused tetracyclic skeleton as described above and its pharmaceutically acceptable salts, solvates, hydrates, polymorphs, cocrystals, tautomers, geometric isomers, enantiomers, diastereomers or mixtures or prodrugs thereof, and a pharmaceutically acceptable carrier, diluent, excipient or a combination thereof. The present invention does not specifically limit the carrier, diluent, and excipient, and can be a carrier, diluent, and excipient suitable for pharmaceutical compositions that are well known to those skilled in the art.

[0020] Based on the same inventive concept, the present invention also provides the use of indole fused tetracyclic skeletons in the preparation of herbicides. The beneficial effects of the present invention are: 1. The present invention efficiently synthesizes an indole-type fused tetracyclic skeleton through multi-step continuous reactions under mild conditions. The technical solution of the present invention provides a convenient and concise synthesis method for the indole-type fused tetracyclic skeleton, and for the first time realizes the efficient construction of an indole-type fused tetracyclic skeleton through a hydrogen migration cyclization reaction based on a "cut-and-stitch" strategy.

[0021] 2. The present invention develops a method for efficiently synthesizing indole-type fused tetracyclic compounds containing multiple functional groups, provides a compound library of indole-type fused tetracyclic skeletons, and provides new model molecules for drug development.

[0022] 3. The present invention provides an experimental basis for the efficient construction of indole-type fused tetracyclic skeletons with good biological activity, and has great practical significance and application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The synthetic process route diagram of the present invention is shown in FIG. DETAILED DESCRIPTION

[0024] The following will combine the contents in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in this specification includes any and all combinations of one or more of the related listed items.

[0026] The experimental methods used in the following examples are conventional methods unless otherwise specified; the reagents, materials, instruments, etc. used in the following examples are all commercially available unless otherwise specified; the reaction vessel used in the following examples is a 25 mL thick-walled pressure-resistant tube.

[0027] Example 1 1. This embodiment provides a method for synthesizing an indole-based fused tetracyclic skeleton, which comprises the following steps: Take 0.13 mmol N-arylmethyl indole in a reaction bottle, add 0.10 mmol o-alkoxy substituted benzaldehyde, 0.03 mmol catalyst, and finally add 1 mL solvent. Control the reaction temperature of the system, keep stirring, and track the reaction by spotting on a thin layer chromatography plate until the raw material reacts completely. After the reaction is completed, use a silica gel column for separation and purification, and evaporate the purified product to obtain the target product.

[0028] The reaction formula is as follows:

[0029] 2. According to the above method, 7 parallel test groups were set up, using different acidic catalysts and solvents. The catalysts were boron trifluoride etherate (BF3·OEt2), copper trifluoromethanesulfonate Cu(OTf)2, camphorsulfonic acid (CSA), p-toluenesulfonic acid ( p -TsOH . H2O); the solvents were dichloroethane (DCE), toluene (Toluene), dimethyl carbonate, and ethyl acetate (EA). The specific acidic catalyst, solvent, reaction temperature and corresponding yield used in the experimental group are shown in Table 1: Table 1 Corresponding yields under different acidic catalysts and solvents

[0030] Note: N-arylmethyl indole (0.13mmol), solvent (1 mL), o-alkoxy substituted benzaldehyde (0.1 mmol), acid catalyst dosage (0.03 mmol); the above yield is the isolated yield. According to the analysis of the above parallel test results, it can be seen that the yield of the product is the highest when boron trifluoride etherate (BF3·OEt2) is used as an acid catalyst.

[0031] 3. According to the above method, set up the following three parallel test groups, using different reaction conditions, such as different reaction temperatures. The specific settings of different test groups are shown in Table 2: Table 2 Reaction yields under different temperature conditions

[0032] Note: Catalyst BF3·OEt2 (0.03 mmol), solvent (1 mL); the above yields are isolated yields.

[0033] According to the analysis of the above parallel test results, the yield of the product is the highest when the synthesis reaction of the present invention is carried out at 120 ° C with ethyl acetate (1 mL) as solvent, N-arylmethyl indole (0.13 mmol), o-alkoxy substituted benzaldehyde (0.1 mmol), and catalyst boron trifluoride etherate (BF3·OEt2) (0.03 mmol).

[0034] In the following examples 2-11, the reaction was carried out according to the operating steps of example 1; 0.13 mmol N-arylmethyl indole was taken in a reaction bottle, 0.1 mmol o-alkoxy substituted benzaldehyde, 0.03 mmol catalyst boron trifluoride ether (BF3·OEt2) were added in sequence, and finally 1 mL ethyl acetate was added. The reaction temperature of the system was controlled to be 120 °C, stirring was continued, and the reaction was tracked by spotting on a thin layer chromatography plate until the raw material reacted completely. After the reaction was completed, a silica gel column was used for separation and purification, and the purified product was rotary evaporated to obtain the target product.

[0035] Example 2 raw material:

[0036] Product 2a: Chemical formula: C 35 H 35 NO3 Structural formula:

[0037] Yield: 95% 1 H NMR (500 MHz, DMSO- d6 ) δ 8.33 (dd, J = 8.2, 4.4 Hz, 1H), 7.56 (q, J= 7.9, 6.0 Hz, 1H), 7.32 – 7.23 (m, 1H), 7.21 – 7.11 (m, 5H), 7.09 (dt, J =8.9, 4.6 Hz, 1H), 6.97 (q, J = 6.5 Hz, 2H), 6.80 – 6.69 (m, 1H), 6.57 (d, J =7.0 Hz, 1H), 6.43 (q, J = 7.6, 5.8 Hz, 1H), 6.32 (t, J = 5.9 Hz, 1H), 5.77(d, J = 4.9 Hz, 1H), 5.58 (dd, J = 16.5, 7.0 Hz, 1H), 5.25 (dd, J = 16.4, 6.3Hz, 1H), 4.11 (d, J = 4.6 Hz, 2H), 3.81 (dd, J = 12.3, 8.1 Hz, 6H), 1.53 –1.34 (m, 9H). 13 C NMR (125 MHz, DMSO- d6) δ 160.0, 157.8, 153.5, 144.1, 137.5,135.9, 135.5, 134.7, 129.2, 128.7, 128.6, 127.8, 127.0, 126.5, 124.2, 121.0,119.6, 119.5, 119.2, 118.0, 109.8, 107.2, 103.5, 98.1, 56.1, 55.8 45.1, 36.9,35.0, 30.4, 24.3.HRMS (ESI) m / z:[M+H] + Calculate for C 35 H 36 NO3 + 518.2690; found:518.2693. Example 3 raw material:

[0038] Product 3a: Chemical formula: C 41 H 39 NO3 Structural formula:

[0039] Yield: 80% 1 H NMR (400 MHz, DMSO -d6 ) δ 8.32 (s, 1H), 7.57 – 7.50 (m, 3H), 7.40(t, J = 7.9 Hz, 4H), 7.33 – 7.24 (m, 2H), 7.21 – 7.12 (m, 3H), 7.00 – 6.90(m, 2H), 6.73 (d, J = 2.3 Hz, 1H), 6.56 (d, J = 2.3 Hz, 1H), 6.38 (t, J = 7.7Hz, 1H), 6.27 (dd, J = 7.6, 1.6 Hz, 1H), 5.76 (s, 1H), 5.59 (d, J = 16.6 Hz,1H), 5.28 (d, J = 16.4 Hz, 1H), 4.15 – 4.02 (m, 2H), 3.81 (d, J = 2.0 Hz, 6H), 1.41 (s, 9H). 13 C NMR (100 MHz, DMSO -d6) δ 159.7, 157.8, 153.5, 143.4,140.4, 138.5, 137.4, 135.7, 135.5, 134.5, 129.3, 129.1, 128.6, 128.3, 127.7,127.1, 127.0, 126.9, 124.2, 121.0, 119.6, 119.6, 119.1, 117.7, 109.8, 107.3,103.5, 98.1, 56.2, 55.8, 45.1, 36.5, 35.0, 30.3, 30.2, 24.2.HRMS (ESI) m / z:[M+H] + Calculate for C 41 H 40 NO3 + 594.3003; found: 594.3007. Example 4 raw material:

[0040] Product 4a: Chemical formula: C 35 H 34 FNO3 Structural formula:

[0041] Yield: 86% 1 H NMR (500 MHz, DMSO -d6 ) δ 8.33 (s, 1H), 7.53 (dd, J = 8.7, 4.4 Hz,1H), 7.15 (d, J = 6.6 Hz, 4H), 7.11 – 7.06 (m, 1H), 7.01 – 6.91 (m, 3H), 6.70(d, J = 2.4 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.44 (t, J = 7.6 Hz, 1H), 6.32– 6.18 (m, 1H), 5.74 (d, J = 4.7 Hz, 1H), 5.57 (d, J = 16.7 Hz, 1H), 5.26 (d,J = 16.4 Hz, 1H), 4.11 – 3.98 (m, 2H), 3.80 (d, J = 8.5 Hz, 6H), 1.42 (s,9H). 13 C NMR (100 MHz, DMSO -d6) δ 159.7, 157.8, 157.5 (d, J = 230.0 Hz), 153.5,144.0, 137.7 (d, J = 2.0 Hz), 134.3, 132.1, 129.0, 128.8, 128.7, 127.9,127.1, 126.6, 124.3, 119.8, 117.6, 110.8 (d, J = 9.0 Hz), 108.8 (d, J = 26.0Hz), 107.9 (d, J = 4.0 Hz), 104.9 (d, J = 23.0 Hz), 103.4, 98.1, 56.1, 55.8,45.2, 37.0, 35.0, 30.3, 24.2.HRMS (ESI) m / z:[M+H] + calcd for C 35 H 35 FNO3 + 536.2596; found:536.2590. Example 5 raw material:

[0042] Product 5a: Chemical formula: C 35 H 34 ClNO3 Structural formula:

[0043] Yield: 71% 1 H NMR (500 MHz, DMSO -d6) δ 8.36 (s, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.25 (d, J = 2.1 Hz, 1H), 7.17 (dt, J = 6.8, 1.1 Hz, 1H), 7.14 (t, J = 2.4Hz, 3H), 7.13 – 7.07 (m, 2H), 6.96 (dd, J = 7.8, 1.7 Hz, 1H), 6.70 (d, J =2.4 Hz, 1H), 6.56 (d, J = 2.4 Hz, 1H), 6.43 (t, J = 7.7 Hz, 1H), 6.23 (dd, J= 7.6, 1.6 Hz, 1H), 5.75 (s, 1H), 5.58 (d, J = 16.5 Hz, 1H), 5.26 (d, J =16.4 Hz, 1H), 4.10 – 4.00 (m, 2H), 3.80 (d, J = 4.6 Hz, 6H), 1.42 (s, 9H). 13 CNMR (100 MHz, DMSO -d6 ) δ 159.7, 157.8, 153.4, 143.9, 137.8, 137.4, 134.2,133.9, 129.5, 129.0, 128.8, 127.9, 127.1, 126.7, 124.4, 124.2, 120.8, 119.8,118.4, 117.5, 111.4, 107.7, 103.4, 98.2, 56.1, 55.8, 45.1, 36.9, 35.0, 30.3,24.0.HRMS (ESI) m / z:[M+H] + Calculate for C 35 H 35 ClNO3 + 552.2300; found: 552.2305. Example 6 raw material:

[0044] Product 6a: Chemical formula: C 35 H 34 BrNO3 Structural formula:

[0045] Yield: 63% 1H NMR (400 MHz, DMSO -d6 ) δ 8.38 (s, 1H), 7.50 (d, J = 8.7 Hz, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.24 (dd, J = 8.6, 2.0 Hz, 1H), 7.19 – 7.05 (m,5H), 6.95 (dd, J = 7.8, 1.7 Hz, 1H), 6.69 (d, J = 2.3 Hz, 1H), 6.55 (d, J =2.4 Hz, 1H), 6.42 (t, J = 7.7 Hz, 1H), 6.21 (dd, J = 7.6, 1.6 Hz, 1H), 5.75(s, 1H), 5.57 (d, J = 16.5 Hz, 1H), 5.25 (d, J = 16.4 Hz, 1H), 4.04 (d, J =3.1 Hz, 2H), 3.80 (d, J = 2.9 Hz, 6H), 1.42 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 )δ 159.7, 157.8, 153.4, 143.9, 137.8, 137.3, 134.2, 134.1, 130.2, 128.9,128.8, 127.9, 127.8, 127.2, 126.7, 124.4, 123.3, 121.4, 119.8, 117.6, 112.2,111.9, 107.7, 103.4, 98.2, 56.2, 55.8, 45.1, 36.9, 35.0, 30.3, 24.1.HRMS(ESI) m / z:[M+H] + Calculate for C 35 H 35 BrNO3 + 596.1795; found: 596.1796. Example 7 raw material:

[0046] Product 7a: Chemical formula: C 39 H 37 NO3 Structural formula:

[0047] Yield: 95% 1H NMR (500 MHz, DMSO -d6 ) δ 8.30 (s, 1H), 7.80 – 7.72 (m, 1H), 7.71 –7.62 (m, 2H), 7.61 – 7.53 (m, 2H), 7.43 – 7.35 (m, 2H), 7.30 – 7.21 (m, 2H),7.18 – 7.12 (m, 1H), 6.98 – 6.93 (m, 1H), 6.90 (dd, J = 7.6, 1.9 Hz, 1H), 6.75 (d, J = 2.3 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.42 – 6.22 (m, 2H), 5.86(s, 1H), 5.61 (d, J = 16.5 Hz, 1H), 5.36 (d, J = 16.4 Hz, 1H), 4.08 (d, J =2.8 Hz, 2H), 3.80 (d, J = 12.8 Hz, 6H), 1.41 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 )δ 159.7, 157.9, 153.5, 141.5, 137.4, 135.6, 135.5, 134.7, 133.3, 132.0,129.1, 128.6, 128.3, 128.1, 127.7, 126.8, 126.6, 126.4, 126.0, 124.2, 121.1,119.6, 119.1, 117.6, 109.9, 107.4, 103.5, 98.1, 56.1, 55.8, 45.1, 37.1, 35.0,30.3, 24.2.HRMS (ESI) m / z:[M+H] + Calculate for C 39 H 38 NO3 + 568.2846; found: 568.2850. Example 8 raw material:

[0048] Product 8a: Chemical formula: C 31 H 35 NO3 Structural formula:

[0049] Yield: 55% 1 H NMR (500 MHz, DMSO- d6 ) δ 8.35 (s, 1H), 7.48 (dd, J = 8.1, 1.0 Hz,1H), 7.19 – 7.07 (m, 2H), 7.02 – 6.92 (m, 2H), 6.59 (s, 2H), 6.48 (t, J = 7.7Hz, 1H), 6.38 (dd, J = 7.7, 1.7 Hz, 1H), 5.31 (s, 2H), 4.29 (s, 2H), 3.85 (s,3H), 3.81 (s, 3H), 1.77 (s, 6H), 1.44 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ159.5, 158.9, 153.7, 142.0, 137.1, 134.4, 131.0, 129.8, 129.2, 126.7, 124.2,122.2, 120.8, 119.9, 119.5, 118.5, 110.0, 105.3, 102.5, 99.7, 56.0, 55.6,44.7, 36.0, 35.0, 30.4, 28.4, 25.9.HRMS (ESI) m / z:[M+H] + Calculate for C 31 H 36 NO3 + 470.2690; found: 470.2693. Example 9 raw material:

[0050] Product 9a: Chemical formula: C 35 H 34 BrNO3 Structural formula:

[0051] Yield: 92% 1 H NMR (400 MHz, DMSO -d6) δ 8.28 (s, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.32 – 7.23 (m, 3H), 7.18– 7.12 (m, 1H), 7.07 – 7.00 (m, 2H), 7.00–6.91 (m, 2H), 6.71 (d, J = 2.3 Hz, 1H), 6.54 (d, J = 2.3 Hz, 1H), 6.39 (t, J = 7.6 Hz,1H), 6.23 (dd, J = 7.6, 1.6 Hz, 1H), 5.65 (s, 1H), 5.56 (d, J = 16.6 Hz, 1H),5.26 (d, J = 16.4 Hz, 1H), 4.08 – 3.97 (m, 2H), 3.79 (d, J = 8.5 Hz, 6H), 1.41 (s, 9H). 13 C NMR (100MHz, DMSO- d6 ) δ 159.8, 157.7, 153.4, 143.5, 137.4,135.4, 135.0, 134.3, 131.5, 130.1, 129.0, 128.6, 126.9, 124.2, 121.1, 119.6,119.5, 119.1, 117.3, 109.9, 107.5, 103.4, 98.1, 56.1, 55.8, 44.9, 36.4, 35.0,30.3, 24.1.HRMS (ESI) m / z:[M+H] + Calculate for C 35 H 35 BrNO3 + 596.1795; found:596.1794. Example 10 raw material:

[0052] Product 10a: Chemical formula: C 36 H 37 NO3 Structural formula:

[0053] Yield: 75% 1 H NMR (500 MHz, DMSO -d6) δ 7.89 (s, 1H), 7.57 – 7.46 (m, 1H), 7.20 (d, J = 7.7 Hz, 2H), 7.14 – 7.04 (m, 3H), 6.98 (d, J = 8.0 Hz, 2H), 6.88 (dd,J = 10.6, 7.3 Hz, 2H), 6.68 (d, J = 3.0 Hz, 1H), 6.41 (d, J = 3.0 Hz, 1H), 6.32 (td, J = 7.6, 2.5 Hz, 1H), 5.96 (d, J = 7.6 Hz, 1H), 5.58 (d, J = 16.9Hz, 1H), 5.38 (d, J = 16.7 Hz, 1H), 3.79 (d, J = 2.6 Hz, 3H), 3.72 – 3.61 (m,2H), 3.24 (d, J = 2.9 Hz, 3H), 2.02 (s, 3H), 1.39 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ 159.3, 158.8, 153.2, 148.6, 140.7, 136.9, 134.5, 131.2, 129.4,129.0, 127.8, 127.4, 127.2, 125.3, 123.8, 123.4, 120.9, 119.7, 119.2, 118.7,110.0, 107.2, 102.7, 100.4, 55.8, 55.6, 44.6, 42.9, 34.9, 30.3, 25.4,24.3.HRMS (ESI) m / z:[M+H] + Calculate for C 36 H 38 NO3 + 532.2846; found: 532.2845. Embodiment 11 raw material:

[0054] Product 11a: Chemical formula: C 36 H 37 NO3 Structural formula:

[0055] Yield: 88% 1 H NMR (500 MHz, DMSO-d6 ) δ 8.29 (s, 1H), 7.17 – 7.10 (m, 4H), 7.09 –7.05 (m, 1H), 7.04 (dd, J = 7.4, 1.8 Hz, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 6.87 – 6.78 (m, 2H), 6.76 (d, J = 2.3 Hz, 1H), 6.53 (d, J = 2.4 Hz, 1H), 6.40(t, J = 7.7 Hz, 1H), 6.25 (dd, J = 7.5, 1.7 Hz, 1H), 5.96 (d, J = 16.4 Hz,1H), 5.69 (s, 1H), 5.60 (d, J = 16.2 Hz, 1H), 4.13 – 3.97 (m, 2H), 3.79 (d, J= 15.3 Hz, 6H), 2.89 (s, 3H), 1.42 (s, 9H). 13 C NMR (100 MHz, DMSO- d6 ) δ 159.6,157.5, 153.5, 144.1, 137.4, 136.1, 135.2, 134.9, 129.2, 129.1, 128.7, 127.8,126.7, 126.5, 124.2, 124.0, 121.3, 119.6, 119.5, 117.4, 117.1, 107.3, 103.4,98.1, 56.1, 55.8, 47.9, 36.7, 35.0, 30.3, 24.2, 20.3.HRMS (ESI) m / z:[M+H] + Calculate for C 36 H 38 NO3 + 532.2846; found: 532.2844. Weed control test results: The compounds of the present invention have the following inhibition rates on the stems and roots of barnyard grass:

[0056] Note: “++++++” indicates that the inhibition range is 90%-100% at a concentration of 50 mg / L; “++++” indicates that the inhibition range is 70%-90% at a concentration of 50 mg / L; “+++” indicates that the inhibition range is 50%-70% at a concentration of 50 mg / L; “++” indicates that the inhibition range is 30%-50% at a concentration of 50 mg / L; “+” indicates that the inhibition range is 10%-30% at a concentration of 50 mg / L.

[0057] Most of the compounds in the present invention have an inhibition rate of more than 70% on the roots and stems of barnyard grass at a concentration of 50 mg / L; the compounds in the present invention have a good effect of inhibiting the growth of roots and stems, and therefore have a good application prospect in weed control.

[0058] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An indole condensed tetracyclic skeleton, characterized in that: Its structural formula is shown in Formula 1: In formula 1, R 1 is any one of a methoxy group and a benzene ring; R 2 is any one of methoxy, fluorine, chlorine, bromine and methyl; R 3 is any one of tert-butyl and methyl; R 4 is any one of substituted benzene, naphthalene ring, and methyl; wherein R 1 , R 2 , R 3 , R 4 They are the same as or different from each other and each independently represents a substituent.

2. The method for synthesizing the indole fused tetracyclic active skeleton according to claim 1, characterized in that: The following steps are involved: N-arylmethyl indole and o-alkoxy substituted benzaldehyde are uniformly mixed in a solvent, and reacted at 100-120°C under the catalysis of Lewis acid to obtain an indole-type fused tetracyclic compound; Wherein, the structural formula of the above-mentioned N-arylmethyl indole is shown in Formula 2: In formula 2, R 1 is any one of a methoxy group and a benzene ring; R 2 Any one of methoxy, fluorine, chlorine, bromine and methyl; Wherein, the structural formula of the above-mentioned o-alkoxy substituted benzaldehyde is shown in Formula 3: In formula 3, R 3 is any one of tert-butyl and methyl; R 4 It is any one of substituted benzene, naphthalene ring and methyl group.

3. The synthesis method according to claim 2, characterized in that The molar ratio of the N-arylmethyl indole to the o-alkoxy substituted benzaldehyde is (1-2):

1.

4. The synthesis method according to claim 2, characterized in that The solvent is ethylene dichloride, toluene, dimethyl carbonate and ethyl acetate.

5. The synthesis method according to claim 2, characterized in that The amount of the solvent is as follows: 10 to 25 L of the solvent is added per mole of N-arylmethyl indole and o-alkoxy substituted benzaldehyde.

6. The synthesis method according to claim 2, characterized in that The Lewis acid catalyst is any one of boron trifluoride etherate, p-toluenesulfonic acid, camphorsulfonic acid, and copper trifluoromethanesulfonate.

7. The synthesis method according to claim 2, characterized in that The amount of the catalyst used is 20 to 100 mol%.

8. Use of the indole fused tetracyclic biologically active skeleton according to claim 1 in the preparation of a herbicide.

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