Preparation method and bacteriostatic application of indole-containing diaryl heptamethylenoxa skeleton

Abstract

The application discloses an indole-containing diaryl heptamethylenzo skeleton, a synthesis method and application thereof. The application provides an indole-containing diaryl heptamethylenzo skeleton structure. The application provides a synthesis method, which comprises the following steps: uniformly mixing substituted indole and o-benzyloxy-substituted benzaldehyde in a solvent, and reacting under acid conditions at 100-120 DEG C to prepare an indole-containing diaryl heptamethylenzo compound. The application also provides application of the indole-containing diaryl heptamethylenzo skeleton in preparation of an antibacterial agent. The application provides a green synthesis method of the indole-containing diaryl heptamethylenzo compound.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical intermediates and chemical synthesis technology, in particular to a kind of indole-containing diaryl heptamethylenzo structure and its synthesis method and application. BACKGROUND

[0002] Diaryl heptamethylenzo structure widely exists in many natural products and drug molecules, and has important application value in medicine and pesticide, for example, doxepin is an antidepressant, and natural product eurotinone has diaryl heptamethylenzo structure, which shows very good antitumor activity. However, the type of the skeleton is not rich enough at present, and there is lack of effective method for constructing diaryl heptamethylenzo structure, which seriously hinders the subsequent biological activity research of structure diverse diaryl heptamethylenzo molecule. Therefore, efficient construction of diaryl heptamethylenzo has important significance for drug development.

[0003]

[0004] For example, in 2020, Huang Xueliang's group of Fujian Institute of Structure Chemistry, Chinese Academy of Sciences realized the cyclization reaction of transition metal palladium-catalyzed o-bromobenzaldehyde and o-hydroxyphenyl hydrazone, and efficiently synthesized diaryl heptamethylenzo ketone structure (Nature Communications, 2020, 11, 461).

[0005]

[0006] Indole is the core structure of many natural products and drug molecules, and diaryl heptamethylenzo structure has significant biological activity, but there is no report on the efficient synthesis method of indole-containing diaryl heptamethylenzo structure. Therefore, developing an efficient and direct method for synthesizing indole-containing diaryl heptamethylenzo structure compound has important significance for developing new bacteriostatic agents and drugs, especially drugs for treating tumors, pain, depression and other diseases. SUMMARY

[0007] The present application aims at the deficiencies of the prior art, and provides a kind of indole-containing diaryl heptamethylenzo structure with biological activity and its synthesis method and application. The indole-containing diaryl heptamethylenzo structure provided in the present application will provide a new model molecule for drug development. The synthesis method of the indole-containing diaryl heptamethylenzo skeleton provided in the present application first adds N-arylmethylindole and o-alkoxy-substituted benzaldehyde by nucleophilic addition / cyclization reaction, and efficiently synthesizes the skeleton in one step. The operation is simple, efficient and practical, and the constructed skeleton contains various functional groups, which is beneficial to the late synthesis and application of the skeleton.

[0008] The technical scheme of the present application is implemented as follows:

[0009] The indole-containing diaryl heptameric oxygen heterocycle skeleton has a structural formula as shown in formula 1.

[0010]

[0011] In formula 1, R 1 is any one of a hydrogen atom, a benzyl group and a methyl group; R 2 is any one of a hydrogen atom and a methyl group; R 3 is any one of a hydrogen atom, fluorine, chlorine, bromine and a methyl group; R 4 is any one of a hydrogen atom and a tert-butyl group; R 5 is any one of a hydrogen atom and a methoxy group; wherein R 1 , R 2 , R 3 , R 4 , R 5 are the same as or different from each other and each independently represent a substituent.

[0012] The compound involved in the present application can exist in the form of one or more stereoisomers. The various isomers include tautomers, geometric isomers, enantiomers, diastereoisomers and the like. These isomers and mixtures of these isomers are all within the protection scope of the present application.

[0013] Based on the same inventive concept, the present application further provides a synthesis method of the indole-containing diaryl heptameric oxygen heterocycle skeleton, a synthesis process route map of the present application is shown in Figure 1 , which comprises the following steps:

[0014] The N-arylmethyl indole and the ortho-alkoxy-substituted benzaldehyde are uniformly mixed in a solvent, and reacted under an acidic condition at 100-120℃ to prepare the indole-containing diaryl heptameric oxygen heterocycle compound.

[0015] The structure of the above-mentioned substituted indole is shown in formula 2.

[0016]

[0017] In formula 2, R 1 is any one of a hydrogen atom, a benzyl group and a methyl group; R 2 is any one of a hydrogen atom and a methyl group; R 3 is any one of a hydrogen atom, fluorine, chlorine, bromine and a methyl group.

[0018] The structure of the above-mentioned ortho-benzyloxy-substituted benzaldehyde is shown in formula 3.

[0019]

[0020] R1is any one of a hydrogen atom, a tert-butyl group; 4 R2is any one of a hydrogen atom, a methoxy group. 5 R2is any one of a hydrogen atom, a methoxy group.

[0021] The reaction can be detected by thin layer chromatography. After the reaction is completed, purification is performed to obtain a purified product of the indole-containing diaryl heptacyclic oxygen heterocycle compound.

[0022] The above reaction process is specifically as follows:

[0023] Two molecules of the substituted indole undergo nucleophilic addition reaction on the ortho-benzyloxy-substituted benzaldehyde under acidic conditions to generate a triaryl methane intermediate 7a, followed by reverse Friedel-Crafts alkylation to generate the intermediate I, and then intramolecular nucleophilic addition cyclization to generate the indole-containing diaryl heptacyclic oxygen heterocycle compound. The synthetic principle route is specifically as follows:

[0024]

[0025] Preferably, the above-mentioned synthetic method is reacted at 120 °C.

[0026] In the above-mentioned synthetic method, the molar ratio of the substituted indole to the ortho-benzyloxy-substituted benzaldehyde is 1: (1-3). Preferably, the molar ratio of the substituted indole to the ortho-benzyloxy-substituted benzaldehyde is 1:1.2.

[0027] In the above-mentioned synthetic method, the solvent is ethanol or methanol.

[0028] In the above-mentioned synthetic method, the amount of the solvent is 10-25 L per mole of the substituted indole and the ortho-benzyloxy-substituted benzaldehyde. Preferably, the amount of the solvent is 10 L per mole of the substituted indole and the ortho-benzyloxy-substituted benzaldehyde.

[0029] In the above-mentioned synthetic 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, camphor sulfonic acid, scandium triflate.

[0030] In the above-mentioned synthetic method, the amount of the acidic catalyst is 20-100 mol%. Preferably, the amount of the catalyst is 30 mol%.

[0031] Based on the same inventive concept, the present application also provides a pharmaceutical composition comprising the indole-containing biaryl heptamethylenedioxycyclic skeleton as described above and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, geometric isomers, enantiomers, diastereomers or mixtures thereof or prodrugs thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof. The present application does not have special limitations on the carrier, diluent, excipient, which can be the carrier, diluent, excipient suitable for pharmaceutical composition known to those skilled in the art.

[0032] Based on the same inventive concept, the present application also provides the use of the indole-containing biaryl heptamethylenedioxycyclic skeleton in bacteriostasis.

[0033] The beneficial effects of the present application are:

[0034] 1. The present application efficiently synthesizes the indole-containing biaryl heptamethylenedioxycyclic skeleton under mild conditions through multi-step continuous reaction, and the technical scheme of the present application provides a convenient and simple synthesis method for the indole-containing biaryl heptamethylenedioxycyclic skeleton.

[0035] 2. The present application develops a method for efficiently synthesizing the indole-containing biaryl heptamethylenedioxycyclic compound containing multiple functional groups, and provides a compound library of the indole-containing biaryl heptamethylenedioxycyclic skeleton, which provides a new model molecule for drug development.

[0036] 3. The present application provides experimental basis for efficient construction of the indole-containing biaryl heptamethylenedioxycyclic skeleton with good biological activity, and has good practical significance and application value. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 The present application is a synthesis process route map. DETAILED DESCRIPTION

[0038] The technical scheme in the embodiments of the present application will be described clearly and completely below in combination with the content in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor belong to the scope of protection of the present application.

[0039] Unless otherwise defined, all technical and scientific terms used in the specification have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. The terms used in the specification of the present application are only for the purpose of describing the specific embodiments and are not used to limit the present application. The term "and / or" used in the specification includes any and all combinations of one or more related listed items.

[0040] 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 commercially available unless otherwise specified; the reaction vessels used in the following examples are 25 mL thick-walled pressure-resistant tubes.

[0041] Example 1

[0042] 1. The present example provides a method for synthesizing a diaryl heptacyclic oxygen heterocycle skeleton containing an indole, comprising the following steps:

[0043] Take 0.13 mmol of substituted indole in a reaction bottle, and then add 0.10 mmol of o-benzyloxy-substituted benzaldehyde and 0.03 mmol of catalyst, and finally add 1 mL of solvent. Control the reaction temperature of the system, continuously stir, and track the reaction by thin layer chromatography until the raw material is completely reacted. After the reaction is completed, separate and purify using a silica gel column, and rotary evaporate the purified product to obtain the target product.

[0044] The reaction formula is as follows:

[0045]

[0046] 2. According to the above method, 7 groups of parallel test groups were set up, using different acidic catalysts and solvents. The catalysts were boron trifluoride etherate (BF3·OEt2), scandium triflate Sc(OTf)3, camphor sulfonic acid (CSA), p-toluene sulfonic acid (p-TsOH), and the solvents were ethanol (EtOH) and methanol (MeOH). The specific acidic catalysts and solvents used in each test group and the corresponding yields are shown in Table 1: p -TsOH . H2O); and the solvents were ethanol (EtOH) and methanol (MeOH). The specific acidic catalysts and solvents used in each test group and the corresponding yields are shown in Table 1:

[0047] Table 1. Corresponding yield table under different acidic catalysts and solvents

[0048]

[0049] Note: Substituted indole (0.13 mmol), solvent (1 mL), o-benzyloxy-substituted benzaldehyde (0.1 mmol), and acidic 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 boron trifluoride etherate (BF3·OEt2) is the acidic catalyst with the highest yield of product.

[0050] 3. According to the above method, the following 3 groups of parallel test groups were set up, using different reaction conditions such as different reaction temperatures. The specific settings of different test groups are shown in Table 2:

[0051] Table 2. Reaction yield table under different temperature conditions

[0052]

[0053] Note: catalyst BF3·OEt2(0.03 mmol), solvent (1 mL); the above yield is the isolated yield.

[0054] According to the above parallel test results analysis can be known: the synthetic reaction of the present application in ethanol (1 mL) as solvent, instead of indole (0.13 mmol), o-benzyloxy substituted benzaldehyde (0.1 mmol), catalyst trifluoroboron ether (BF3·OEt2) (0.03 mmol), 120 ℃ under the condition of reaction, the yield of the product is the highest.

[0055] In the following examples 2-11, according to the operation steps of example 1; take 0.13 mmol of substituted indole in the reaction bottle, add 0.1 mmol of o-benzyloxy substituted benzaldehyde, 0.03 mmol of catalyst trifluoroboron ether (BF3·OEt2) in turn, and finally add 1 mL of ethanol. Control the reaction temperature of the system to be 120 ℃, continue to stir, and track the reaction by thin layer chromatography plate sampling until the raw material is completely reacted. After the reaction is completed, the product is separated and purified by silica gel column, and the purified product is rotary evaporated to obtain the target product.

[0056] Example 2

[0057] Raw materials:

[0058] Product 2a: Chemical formula: C 25 H 23 NO3

[0059] Structural formula:

[0060] Yield: 69%

[0061] 1 H NMR (500 MHz, DMSO -d6) δ 7.37 - 7.29 (m, 2H), 7.24 - 7.15 (m, 2H), 7.06 - 7.11 (m, 1H), 6.98 - 6.86 (m, 3H), 6.73 (d, J = 2.4 Hz, 1H), 6.62 (d, J = 1.4 Hz, 1H), 6.54 (d, J = 2.4 Hz, 1H), 5.96 (d, J = 1.5 Hz, 1H), 5.70 (d, J = 12.6 Hz, 1H), 4.64 (d, J = 12.8 Hz, 1H), 3.96 (s, 3H), 3.78 (s, 3H), 3.64 (s, 3H). 13 C NMR (125 MHz, DMSO-d6) δ 159.6, 157.6, 157.3, 138.1, 137.5, 133.3, 128.9, 128.0, 126.2, 122.9, 121.7, 121.5, 120.5, 119.7, 119.6, 119.0, 110.0, 106.5, 98.9, 69.5, 56.5, 55.7, 38.0, 32.6. HRMS (ESI) m / z: [M+H] + calcd for C 25 H 24 NO3 + 386.1751; found: 386.1753.

[0062] Example 3

[0063] Starting materials:

[0064] Product 3a: Chemical Formula: C 37 H 39 NO5

[0065] Structural Formula:

[0066] Yield: 84%

[0067] 1 H NMR (500 MHz, DMSO -d6) δ 7.36 - 7.23 (m, 3H), 7.17 (d, J = 7.8 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 6.93 (t, J = 7.6 Hz, 1H), 6.90 - 6.81 (m, 2H), 6.58 (d, J = 2.5 Hz, 1H), 6.44 (d, J = 2.5 Hz, 1H), 6.32 (d, J = 2.7 Hz, 1H), 6.20 (d, J = 2.2 Hz, 2H), 5.88 (s, 1H), 5.54 (d, J = 14.4 Hz, 1H), 5.21 (s, 2H), 4.80 (d, J = 14.4 Hz, 1H), 3.82 (s, 3H), 3.76 (s, 3H), 3.63 (s, 6H), 1.31 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ 161.0, 159.2, 157.7, 157.6, 141.2, 141.1, 138.9, 136.4, 134.0, 130.2, 128.0, 127.0, 126.1, 122.6, 121.3, 121.1, 120.0, 119.5, 119.0, 110.4, 105.3, 104.1, 98.9, 98.2, 71.2, 56.4, 55.6, 55.5, 49.2, 38.6, 35.1, 30.8. HRMS (ESI) m / z: [M+H] + calcd for C 37 H 40 NO5 + 578.2901; found: 578.2903.

[0068] Example 4

[0069] Starting materials:

[0070] Product 4a: Chemical Formula: C 38 H 41 NO5

[0071] Structural Formula:

[0072] Yield: 72%

[0073] 1H NMR (400 MHz, DMSO -d6 ) δ 7.32 (dd, J = 7.7, 1.6 Hz, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.14 (dd, J = 7.9, 1.6 Hz, 1H), 6.94– 6.85 (m, 2H), 6.79 –6.73(m, 1H), 6.53 (d, J = 2.5 Hz, 1H), 6.45 (d, J = 2.4Hz, 1H), 6.32 (t, J = 2.3 Hz, 1H), 5.96 (d, J = 2.3 Hz, 2H), 5.90 (s, 1H),5.51 (d, J = 14.4 Hz, 1H), 5.25 (s, 2H), 4.83 (d, J = 14.4 Hz, 1H), 3.75 (d,J = 4.0 Hz, 6H), 3.60 (s, 6H), 2.12 (s, 3H), 1.31 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ 161.1, 159.1, 158.1, 158.0, 141.5, 140.9, 138.7, 136.2, 134.7,133.1, 130.2, 127.4, 125.8, 122.8, 121.0, 120.3, 119.7, 118.8, 115.5, 109.4,104.4, 103.8, 98.4, 98.2, 72.7, 56.3, 55.6, 55.4, 45.7, 35.0, 30.7, 10.7.HRMS (ESI) m / z: [M+H] + calcd for C 38 H 42 NO5 + 592.3058; found: 592.3059.

[0074] Example 5

[0075] Starting materials:

[0076] Product 5a: Chemical Formula: C 37 H 38 FNO5

[0077] Structural Formula:

[0078] Yield: 85%

[0079] 1 H NMR (400 MHz, DMSO -d6 ) δ 7.35 – 7.29 (m, 1H), 7.18 – 7.09 (m, 3H), 7.00 – 6.90 (m, 2H), 6.71 (dd, J = 11.6, 7.7 Hz, 1H), 6.45 (d, J = 2.4 Hz, 1H), 6.37 (d, J = 2.4 Hz, 1H), 6.31 (t, J = 2.2 Hz, 1H), 6.19 (d, J = 2.3 Hz, 2H), 6.06 (s, 1H), 5.53 (d, J = 15.9 Hz, 1H), 5.20 (s, 2H), 4.87 (d, J = 15.7 Hz, 1H), 3.74 (s, 3H), 3.69 (s, 3H), 3.61 (s, 6H), 1.30 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ 161.0, 159.0, 158.6, 157.8, 156.9 (d, J = 244.0 Hz), 141.7, 140.8, 138.9, 138.5 (d, J = 12.0 Hz), 138.4, 129.1, 128.8, 126.1, 123.7, 121.6 (d, J = 7.0 Hz), 120.2, 118.5 (d, J = 5.0 Hz), 115.7 (d, J = 19.0 Hz), 107.1, 105.5, 104.4 (d, J = 20.0 Hz), 102.3, 98.7, 97.8, 73.8, 56.4, 55.5, 55.4, 49.6, 38.7, 38.7, 35.0, 31.0. HRMS (ESI) m / z: [M+H] + calcd for C 37 H 39 FNO5 + 596.2807; found: 596.2808.

[0080] Example 6

[0081] Starting materials:

[0082] Product 6a: Chemical Formula: C 31 H 27 NO3

[0083] Structural Formula:

[0084] Yield: 93%

[0085] 1 H NMR (500 MHz, DMSO -d6 ) δ 7.24 - 7.18 (m, 2H), 7.16 - 7.11 (m, 2H), 7.10 - 7.04 (m, 3H), 6.97 - 6.87 (m, 3H), 6.83 - 6.74 (m, 3H), 6.69 (d, J = 1.4 Hz, 1H), 6.62 (d, J = 2.5 Hz, 1H), 6.44 (d, J = 2.5 Hz, 1H), 5.86 (d, J = 1.4 Hz, 1H), 5.60 (d, J = 12.7 Hz, 1H), 5.19 (s, 2H), 4.54 (d, J = 12.7 Hz, 1H), 3.84 (s, 3H), 3.65 (s, 3H). 13 C NMR (125 MHz, DMSO -d6 ) δ 159.6, 157.5, 157.3, 138.9, 138.0, 137.1, 133.3, 128.9, 128.6, 127.7, 127.6, 127.1, 126.5, 126.5, 123.0, 123.0, 121.8, 121.6, 120.4, 120.4, 120.3, 119.9, 119.3, 110.7, 106.7, 99.0, 69.2, 56.5, 55.7, 49.3, 38.1. HRMS (ESI) m / z: [M+H] + calcd for C 31 H 28 NO3 + 462.2064; found: 462.2066.

[0086] Example 7

[0087] Starting Material:

[0088] Product 7a: Chemical Formula: C 37 H38 ClNO5

[0089] Structure:

[0090] Yield: 75%

[0091] 1 H NMR (400 MHz, DMSO -d6 ) δ 7.41 – 7.30 (m, 2H), 7.23 – 7.15 (m, 2H), 7.03 – 6.92 (m, 3H), 6.58 (d, J = 2.4 Hz, 1H), 6.44 (d, J = 2.5 Hz, 1H), 6.33 (t, J = 2.3 Hz, 1H), 6.19 (d, J = 2.2 Hz, 2H), 5.83 (d, J = 1.0 Hz, 1H), 5.49 (d, J = 14.8 Hz, 1H), 5.22 (s, 2H), 4.81 (d, J = 14.7 Hz, 1H), 3.82 (s, 3H), 3.75 (s, 3H), 3.63 (s, 6H), 1.30 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ 161.0, 159.3, 157.9, 157.6, 141.3, 140.9, 138.9, 134.8, 134.3, 130.1, 129.7, 128.0, 126.2, 123.8, 122.9, 121.2, 120.6, 119.8, 118.8, 112.1, 105.3, 103.9, 99.0, 98.2, 72.0, 56.4, 55.6, 55.5, 49.4, 38.4, 35.1, 30.8. HRMS (ESI) m / z: [M+H] + calcd for C 37 H 39 ClNO5 + 612.2511; found: 612.2512.

[0092] Example 8

[0093] Starting material:

[0094] Product 8a: Chemical Formula: C 37 H 38 BrNO5

[0095] Structure:

[0096] Yield: 76%

[0097] 1 H NMR (400 MHz, DMSO -d6 ) δ 7.40 – 7.31 (m, 2H), 7.28 (d, J = 8.8 Hz, 1H), 7.19 (dd, J = 7.9, 1.7 Hz, 1H), 7.11 (dd, J = 8.7, 2.0 Hz, 1H), 6.98 – 6.91 (m, 2H), 6.58 (d, J = 2.4 Hz, 1H), 6.44 (d, J = 2.4 Hz, 1H), 6.33 (t, J = 2.3 Hz, 1H), 6.18 (d, J = 2.3 Hz, 2H), 5.82 (d, J = 1.0 Hz, 1H), 5.49 (d, J = 14.8 Hz, 1H), 5.22 (s, 2H), 4.81 (d, J = 14.7 Hz, 1H), 3.83 (s, 3H), 3.75 (s, 3H), 3.62 (s, 6H), 1.30 (s, 9H). 13 C NMR (100 MHz, DMSO -d6 ) δ 161.0, 159.3, 157.9, 157.6, 141.3, 140.9, 138.9, 135.1, 134.2, 130.1, 129.5, 128.7, 126.2, 123.7, 122.9, 121.9, 120.6, 119.7, 112.6, 111.8, 105.3, 104.0, 99.0, 98.2, 72.0, 56.4, 55.6, 55.5, 49.4, 38.4, 35.1, 30.8. HRMS (ESI) m / z: [M+H] + calcd for C 37 H 39 BrNO5 + 656.2006; found: 656.2008.

[0098] Example 9

[0099] Starting materials:

[0100] Product 9a: Chemical Formula: C 37 H 38 FNO5

[0101] Structural Formula:

[0102] Yield: 78%

[0103] 1 H NMR (500 MHz, DMSO- -d6 ) δ 7.32 (dd, J = 7.7, 1.6 Hz, 1H), 7.22 - 7.14 (m, 3H), 6.92 (t, J = 7.7 Hz, 1H), 6.82 (d, J = 1.1 Hz, 1H), 6.73 (td, J = 9.3, 2.4 Hz, 1H), 6.57 (d, J = 2.4 Hz, 1H), 6.43 (d, J = 2.4 Hz, 1H), 6.33 (t, J = 2.3 Hz, 1H), 6.21 (d, J = 2.3 Hz, 2H), 5.84 (s, 1H), 5.49 (d, J = 14.6 Hz, 1H), 5.17 (s, 2H), 4.79 (d, J = 14.5 Hz, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 3.63 (s, 6H), 1.29 (s, 9H). 13 C NMR (100 MHz, DMSO- d6 ) δ 161.0, 159.3, 159.1 (d, J = 233.0 Hz), 157.7 (d, J = 11.0 Hz), 141.2, 140.9, 138.9, 136.5 (d, J = 13.0 Hz), 134.1, 130.1, 128.5 (d, J = 3.0 Hz), 126.2, 123.8, 122.7, 120.8, 120.5 (d, J = 10.0 Hz), 120.4, 107.4 (d, J = 24.0 Hz), 105.4, 104.0, 99.0, 98.1, 96.9, 96.6, 71.8, 56.4, 55.6, 55.5, 49.3, 38.5, 35.1, 30.7. HRMS (ESI) m / z: [M+H] + calcd for C 37 H 39 FNO5+ 596.2807; found: 596.2808.

[0104] Example 10

[0105] Starting materials:

[0106] Product 10a: Chemical Formula: C 38 H 41 NO5

[0107] Structure:

[0108] Yield: 61%

[0109] 1 H NMR (400 MHz, DMSO -d6 ) δ 7.35 (dd, J = 7.6, 1.6 Hz, 1H), 7.24 – 7.13 (m, 2H), 6.92 (t, J = 7.6 Hz, 1H), 6.80 – 6.66 (m, 3H), 6.56 (d, J = 2.5 Hz, 1H), 6.42 (d, J = 2.4 Hz, 1H), 6.31 (t, J = 2.3 Hz, 1H), 5.89 (d, J = 2.2 Hz, 2H), 5.85 (s, 1H), 5.54 (d, J = 14.7 Hz, 1H), 5.48 – 5.32 (m, 2H), 4.81 (d, J = 14.7 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 3.59 (s, 6H), 2.38 (s, 3H), 1.30 (s, 9H). 13 C NMR (125 MHz, DMSO -d6 ) δ 161.1, 159.2, 157.8, 157.7, 143.6, 141.2, 138.9, 135.1, 134.7, 130.2, 130.0, 128.2, 126.1, 124.1, 122.7, 121.1, 120.9, 119.8, 119.3, 117.6, 103.8, 103.7, 98.4, 98.1, 72.0, 56.4, 55.6, 55.4, 51.6, 38.5, 35.1, 30.8, 19.5. HRMS (ESI) m / z: [M+H] + calcd for C38 H 42 NO5 + 592.3058; found: 592.3055.

[0110] Example 11

[0111] Starting materials:

[0112] Product 11a: Chemical Formula: C 28 H 29 NO2

[0113] Structural Formula:

[0114] Yield: 70%

[0115] 1 H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 8.4 Hz, 1H), 7.26 - 7.17 (m, 4H), 7.14 - 7.09 (m, 1H), 6.98 - 6.89 (m, 2H), 6.80 (dd, J = 8.4, 2.7 Hz, 1H), 6.63 (d, J = 2.8 Hz, 1H), 6.56 (d, J = 1.2 Hz, 1H), 5.49 (d, J = 14.2 Hz, 1H), 5.34 (d, J = 1.1 Hz, 1H), 4.83 (d, J = 14.2 Hz, 1H), 3.77 (s, 3H), 3.62 (s, 3H), 1.36 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 158.5, 157.2, 141.6, 137.7, 137.1, 133.7, 132.9, 131.4, 129.5, 128.2, 126.6, 126.0, 122.2, 121.2, 119.8, 119.7, 118.7, 112.8, 112.5, 109.1, 71.8, 55.3, 48.8, 35.2, 32.7, 30.6. HRMS (ESI) m / z: [M+H] + calcd for C 28 H 30 NO2 + 412.2271; found: 412.2273.

[0116] The bacteriostatic test results: the compound of the present application respectively has the inhibition rate of 62% to botrytis cinerea

[0117]

[0118] The inhibition rate of most of the compounds in the present application to botrytis cinerea is above 62% at the concentration of 50 mg / L; the compounds in the present application have better effect of inhibiting the growth of botrytis cinerea, and therefore have good application prospect in bacteriostasis.

[0119] The above merely describes the preferred embodiments of the present application and is not used to limit the present application, and any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. Use of an indole-containing biologically active diaromatic heptoxa-cyclic skeleton for the preparation of an antibacterial agent, characterized in that, The structural formula is shown as formula 1: In Formula 1, R 1 is any one of a hydrogen atom, a benzyl group, and a methyl group; R 2 is any one of a hydrogen atom and a methyl group; R 3 is any one of a hydrogen atom, fluorine, chlorine, bromine, and a methyl group; R 4 is any one of a hydrogen atom and a tert-butyl group; R 5 is any one of a hydrogen atom and a methoxy group; wherein R 1 , R 2 , R 3 , R 4 , and R 5 are the same as or different from each other, and each independently represents a substituent.

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