A spiral-ring bicolor full skeleton and its application in the control of wheat stem base rot.

Abstract

This invention discloses a method for constructing spirocyclic bicolor full-skeleton compounds in one step based on a negative hydrogen migration strategy. It also clarifies the agricultural activity and application value of these compounds in the control of wheat stem rot, belonging to the field of organic pesticide technology. The spirocyclic bicolor full-skeleton compounds described in this invention are a class of heterocyclic compounds with unique three-dimensional rigid structures and broad-spectrum biological activity. In the agricultural field, they exhibit excellent inhibitory potential against *Fusarium graminearum* (the pathogen causing wheat stem rot), serving as important lead skeletons for the creation of novel fungicides with broad application prospects.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceutical intermediates and organic pesticides, specifically to the synthesis of a spirocyclic bicolor full-skeletal compound with fungicidal activity, and the application of such a skeleton compound in the control of wheat stem base rot, particularly suitable for the green control of wheat stem base rot caused by drug-resistant Fusarium graminearum. Background Technology

[0002] Wheat stem rot is a key biological factor threatening the scale and efficiency of wheat cultivation. Statistics show that wheat yield reduction due to stem rot can reach 10%-30% annually, jeopardizing agricultural production and food security. Chemical fungicides are the main control method, but their overuse and long-term single-use have led to problems such as pathogen resistance and pesticide residues. Spirocyclic compounds, due to their unique three-dimensional rigid structure, possess the outstanding advantages of multiple targets and low resistance development, making them an important research direction for developing green pesticides. Spirocyclic bicolor full-framework compounds, as an important branch, have even more significant structural advantages, enabling multi-target action and effectively inhibiting the evolution of pathogen resistance. Existing commonly used fungicides generally have limitations such as prominent pathogen resistance and easy phytotoxicity, making it difficult to meet the needs of efficient field control. Therefore, developing novel fungicides based on spirocyclic bicolor full-framework compounds that combine high-efficiency antibacterial activity, resistance resistance, and environmental friendliness, and expanding their application in the control of wheat stem rot, has significant theoretical research value and practical application significance.

[0003] 4-Hydroxycoumarin is a derivative of coumarin with a hydroxyl group on its backbone. It is an important precursor in pesticide development, and its derivatives often exhibit good biological activity. Therefore, new compounds derived from 4-hydroxycoumarin are of great significance for the development of novel active molecules. Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of existing technologies by providing a bioactive spirocyclic bicolor full-skeletal framework, its synthesis method, and its applications. The spirocyclic bicolor full-skeletal framework provided by this invention will offer novel model molecules for drug development. The synthesis method of the spirocyclic bicolor full-skeletal framework provided by this invention is green, efficient, and simple to operate.

[0005] The technical solution of this invention is implemented as follows: A helical ring bicolor full skeleton, characterized in that its structural formula is as shown in Formula 1:

[0006] In Equation 1, R 1 It is any one of hydrogen, fluorine, chlorine, bromine, methyl, and methoxy; R 2 R is either methyl or tert-butyl. 3It is any one of phenyl, p-methylphenyl, p-bromophenyl, 3-methoxyphenyl, naphthyl, oxapzin derivatives, and diclofenac derivatives; R 4 R is any one of hydrogen atom and methyl group. 1 R 2 R 3 R 4 Whether they are the same or different, each represents a substituent independently.

[0007] The compounds involved in this invention can exist in one or more stereoisomers. These isomers include tautomers, geometric isomers, enantiomers, diastereomers, etc. All such isomers and mixtures thereof are within the scope of this invention.

[0008] Based on the same inventive concept, this invention also provides a method for synthesizing a spirocyclic bicolor full skeleton, and the synthesis process route diagram of this invention is as follows: Figure 1 As shown, it includes the following steps: 4-hydroxycoumarin and salicylaldehyde derivative were mixed evenly in a solvent and reacted under alkaline conditions at 100 ℃~120 ℃ to prepare spirocyclic bicolor spherical compounds. The structural formula of the above-mentioned 4-hydroxycoumarin is shown in Formula 2:

[0009] In Equation 2, R 1 It can be any one of hydrogen atom, fluorine, chlorine, methyl, or methoxy. The structural formula of the above-mentioned salicylaldehyde derivative is shown in Formula 3:

[0010] In Equation 3, R 2 It is either methyl or tert-butyl; R 3 It is any one of phenyl, p-methylphenyl, p-bromophenyl, 3-methoxyphenyl, naphthyl, oxapzin derivatives, and diclofenac derivatives; R 4 It can be any one of hydrogen atom or methyl group.

[0011] The above reaction can be detected by thin-layer chromatography. After the reaction is complete, purification is performed to obtain the purified product of the spirocyclic bicolor full-skeletal compound.

[0012] Preferably, the synthesis method described above involves reacting at 120 °C.

[0013] In the synthesis method described above, the molar ratio of 4-hydroxycoumarin to salicylaldehyde derivative is (1-2):1, preferably, the molar ratio of 4-hydroxycoumarin to salicylaldehyde derivative is 1.3:1.

[0014] In the synthesis method described above, the solvent is 1,2-dichloroethane, dichloromethane, toluene, or tetrahydrofuran.

[0015] In the synthesis method described above, the amount of solvent used is 10-25 L per mole of 4-hydroxycoumarin and salicylaldehyde derivative. Preferably, the amount of solvent used is 10 L per mole of 4-hydroxycoumarin and salicylaldehyde derivative.

[0016] In the synthesis method described above, the basic catalyst is added before the reaction. Preferably, the catalyst is any one of morpholine, piperidine, and triethylamine.

[0017] In the synthesis method described above, the amount of the alkaline catalyst used is 50–200 mol%. Preferably, the amount of the catalyst used is 100 mol%.

[0018] Based on the same inventive concept, this invention also provides a pharmaceutical composition comprising the spirocyclic bicolor full skeleton as described above, and its pharmaceutically acceptable salts, solvates, hydrates, polycrystalline forms, cocrystals, tautomers, geometric isomers, enantiomers, diastereomers, or mixtures thereof, or prodrugs, and pharmaceutically acceptable carriers, diluents, excipients, or combinations thereof. This invention does not specifically limit the carriers, diluents, or excipients, and may use carriers, diluents, or excipients well known to those skilled in the art suitable for pharmaceutical compositions.

[0019] Based on the same inventive concept, this invention also provides the application of spirocyclic bicolor full skeleton in the preparation of bactericides.

[0020] The beneficial effects of this invention are: 1. This invention efficiently synthesizes a spirocyclic bicolor full skeleton under green and mild conditions.

[0021] 2. This invention provides experimental evidence for the efficient construction of a spirocyclic bicolor full skeleton with good biological activity, and has great practical significance and application value. Attached Figure Description

[0022] Figure 1 This is a flowchart of the synthesis process of the present invention. Detailed Implementation

[0023] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the invention. The term "and / or" as used in this specification includes any and all combinations of one or more of the associated listed items.

[0025] Unless otherwise specified, 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; the reaction vessels used in the following examples are 25 mL thick-walled pressure-resistant tubes.

[0026] Example 1 1. This embodiment provides a method for synthesizing a spirotoroidal bicolor full skeleton, which includes the following steps: 0.1 mmol of salicylaldehyde derivative was added to a reaction flask, followed by 1 mL of solvent, 0.1 mmol of catalyst, and finally 0.13 mmol of 4-hydroxycoumarin. The reaction temperature was controlled, and the mixture was continuously stirred. The reaction was monitored by spotting the sample onto a thin-layer chromatography plate until the reactants were completely reacted. After the reaction was complete, the product was purified using a silica gel column chromatography method, and the purified product was obtained by rotary evaporation.

[0027] The reaction formula is as follows:

[0028] 3. Following the above method, 10 parallel experimental groups were established, each using different alkaline catalysts, solvents, reaction temperatures, and catalyst dosages. The catalysts were piperidine, morpholine, and triethylamine; the solvents were 1,2-dichloroethane, dichloromethane, toluene, or tetrahydrofuran. The specific alkaline catalysts, solvents, reaction temperatures, catalyst dosages, and corresponding yields used in each experimental group are shown in Table 1. Table 1. Yields under different alkaline catalysts, solvents, and temperatures.

[0029] Note: 4-hydroxycoumarin (0.13 mmol), solvent (1 mL), salicylaldehyde derivative (0.1 mmol), amount of alkaline catalyst (0.1 mmol); the above yields are separation yields.

[0030] Based on the analysis of the parallel experimental results above, it can be seen that the synthesis reaction of the present invention yields the highest product yield when using 1,2-dichloroethane (1 mL) as solvent, 4-hydroxycoumarin (0.13 mmol), salicylaldehyde derivative (0.1 mmol), morpholine catalyst (0.1 mmol), and reacting at 120 °C.

[0031] In Examples 2-22 below, the reaction was carried out according to the operating procedure of Example 1. 0.1 mmol of salicylaldehyde derivative was placed in a reaction flask, followed by the sequential addition of 1 mL of 1,2-dichloroethane, 0.1 mmol of morpholine catalyst, and finally 0.13 mmol of 4-hydroxycoumarin. The reaction temperature was controlled at 120 °C, and the mixture was continuously stirred. The reaction was monitored by spotting the sample onto a thin-layer chromatography plate until the reactants were completely reacted. After the reaction was complete, the product was purified using a silica gel column chromatography method, and the purified product was obtained by rotary evaporation.

[0032] Example 2 raw material:

[0033] Product 2: Chemical formula: C 23 H 24 O4 Structural formula:

[0034] Yield: 88% 1 H NMR (500 MHz, CDCl3) δ 7.94 (dd, J = 7.8, 1.7 Hz, 1H), 7.71-7.65 (m,1H), 7.30 (td, J = 7.5, 1.0 Hz, 1H), 7.23 (dd, J = 8.3, 1.0 Hz, 1H), 7.15 (dd, J = 7.9, 1.6 Hz, 1H), 7.11-7.03 (m, 1H), 6.91 (t, J = 7.6 Hz, 1H), 3.72 (dd, J =17.4, 1.0 Hz, 1H), 3.19 (d, J = 17.4 Hz, 1H), 1.43 (s, 3H), 1.36 (s, 9H), 1.29 (s, 3H). 13 C NMR(125 MHz, CDCl3) δ 191.0, 167.2, 154.9, 150.3, 137.8, 137.3,127.1, 126.5, 125.1, 124.2, 121.1, 120.7, 120.1, 117.5, 61.6, 34.6, 29.8,28.5, 25.1, 22.9.HRMS (ESI) m / z:[M+H] +calcd for C 23 H 25 O4 + 365.4485; found: 365.4488. Example 3 raw material:

[0035] Product 3: Chemical formula: C 24 H 26 O4 Structural formula:

[0036] Yield: 78% 1 H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 2.3 Hz, 1H), 7.48 (dd, J = 8.4, 2.3 Hz, 1H), 7.15 (dd, J = 7.8, 1.6 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 7.06(dd, J = 7.5, 1.6 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H), 3.71 (d, J = 17.3 Hz, 1H), 3.17 (d, J = 17.4 Hz, 1H), 2.40 (s, 3H), 1.43 (s, 3H), 1.36 (s, 9H), 1.28 (s, 3H). 13 C NMR(125 MHz, CDCl3) δ 191.2, 167.4, 153.0, 150.3, 138.1, 137.8, 135.0,126.8, 126.4, 124.2, 121.2, 120.7, 119.7, 117.2, 61.4, 34.6, 29.8, 28.5,25.1, 22.9, 20.6.HRMS (ESI) m / z:[M+H] + calcd for C 24 H 27 O4 + 379.4755; found: 379.4756. Example 4 raw material:

[0037] Product 4: Chemical formula: C 24 H 26 O5 Structural formula:

[0038] Yield: 89% 1 H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 3.1 Hz, 1H), 7.24 (dd, J = 9.0,3.1 Hz, 1H), 7.16 (s, 1H), 7.14 (s, 1H), 7.06 (dd, J = 7.6, 1.5 Hz, 1H), 6.91(t, J = 7.6 Hz, 1H), 3.86 (s, 3H), 3.69 (d, J = 17.4 Hz, 1H), 3.19 (d, J = 17.4Hz, 1H), 1.43 (s, 3H), 1.36 (s, 9H), 1.29 (s, 3H). 13 C NMR(125 MHz, CDCl3) δ191.1, 167.4, 156.6, 150.3, 149.3, 137.8, 126.4, 125.4, 124.2, 121.1, 120.7,120.2, 118.8, 108.0, 61.1, 56.0, 34.6, 29.8, 28.6, 25.0, 23.0.HRMS (ESI) m / z:[M+H] + calcd for C 24 H 27 O5 + 395.4745; found: 395.4748. Example 5 raw material:

[0039] Product 5: Chemical formula: C 23 H 23 FO4 Structural formula:

[0040] Yield: 54% 1H NMR (500 MHz, CDCl3) δ 7.59 (dd, J = 7.6, 3.2 Hz, 1H), 7.42-7.35 (m,1H), 7.23 (dd, J = 9.0, 4.1 Hz, 1H), 7.16 (dd, J = 7.8, 1.7 Hz, 1H), 7.06 (dd, J = 7.5, 1.5 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 3.68 (d, J = 17.4 Hz, 1H), 3.21(d, J = 17.4 Hz, 1H), 1.43 (s, 3H), 1.36 (s, 9H), 1.29 (s, 3H). 13 C NMR (125 MHz, CDCl3) δ 190.3, 166.8, 160.1 (d, J = 245.0 Hz), 151.0, 150.2, 137.9, 126.4,124.5 (d, J = 25.0 Hz), 124.3, 120.9, 120.8, 119.4 (d, J = 7.5 Hz), 112.6 (d, J = 25.0 Hz), 61.3, 34.6, 29.8, 28.6, 25.0, 23.0.HRMS (ESI) m / z:[M+H] + calcd forC 23 H 24 FO4 + 383.4389; found: 383.4386. Example 6 raw material:

[0041] Product 6: Chemical formula: C 23 H 23 ClO4 Structural formula:

[0042] Yield: 76% 1 H NMR (500 MHz, CDCl3) δ 7.89 (d, J= 2.6 Hz, 1H), 7.62 (dd, J = 8.8, 2.6 Hz, 1H), 7.20 (d, J = 8.7 Hz, 1H), 7.16 (dd, J = 7.8, 1.6 Hz, 1H), 7.06(dd, J = 7.6, 1.5 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 3.68 (d, J = 17.4 Hz, 1H), 3.20 (d, J = 17.4 Hz, 1H), 1.43 (s, 3H), 1.36 (s, 9H), 1.29 (s, 3H). 13 C NMR(125MHz, CDCl3) δ 190.0, 166.6, 153.3, 150.2, 137.9, 137.0, 130.8, 126.5, 126.4,124.3, 120.9, 120.8, 120.8, 119.2, 61.6, 34.6, 29.8, 28.6, 25.0, 22.9.HRMS(ESI) m / z:[M+H] + calcd for C 23 H 24 ClO4 + 399.8905; found: 399.8903. Example 7 raw material:

[0043] Product 7: Chemical formula: C 24 H 26 O5 Structural formula:

[0044] Yield: 71% 1 H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 8.7 Hz, 1H), 7.15 (dd, J = 7.8, 1.6 Hz, 1H), 7.06 (dd, J = 7.6, 1.5 Hz, 1H), 6.90 (t, J = 7.6 Hz, 1H), 6.81(dd,J = 8.8, 2.4 Hz, 1H), 6.65 (d, J = 2.4 Hz, 1H), 3.91 (s, 3H), 3.76 (d, J =17.4 Hz, 1H), 3.11 (d, J = 17.4 Hz, 1H), 1.44 (s, 3H), 1.37 (s, 9H), 1.28 (s, 3H). 13 C NMR(125 MHz, CDCl3) δ 189.2, 167.4, 166.9, 156.9, 150.3, 137.7, 129.0,126.5 124.1, 121.2, 120.6, 113.6, 112.6, 101.1, 61.0, 56.1, 34.6, 29.8, 28.5,25.1, 22.7.HRMS (ESI) m / z:[M+H] + calcd for C 24 H 27 O5 + 395.4745; found: 395.4748. Example 8 raw material:

[0045] Product 8: Chemical formula: C 23 H 23 BrO4 Structural formula:

[0046] Yield: 70% 1 H NMR (500 MHz, CDCl3) δ 7.80 (d, J = 8.3 Hz, 1H), 7.51 – 7.39 (m, 2H), 7.16 (dd, J = 7.8, 1.7 Hz, 1H), 7.06 (dd, J = 7.5, 1.5 Hz, 1H), 6.91 (t, J = 7.6Hz, 1H), 3.69 (d, J = 17.4 Hz, 1H), 3.18 (d, J = 17.4 Hz, 1H), 1.43 (s, 3H), 1.36 (s, 9H), 1.28 (s, 3H).13 C NMR (125 MHz, CDCl3) δ 190.1, 166.5, 155.0,150.2, 137.9, 131.7, 128.6, 128.3, 126.4, 124.3, 120.8, 120.7, 118.8, 61.7,34.6, 29.8, 28.56, 25.0, 22.9. HRMS (ESI) m / z:[M+H] + calcd for C 23 H 24 BrO4 + 444.3445; found: 444.3448. Example 9 raw material

[0047] Product 9: Chemical formula: C 20 H 26 O4 Structural formula:

[0048] Yield: 81% 1 H NMR (500 MHz, CDCl3) δ 7.86 (dd, J = 7.8, 1.8 Hz, 1H), 7.64 – 7.59(m, 1H), 7.25 – 7.20 (m, 1H), 7.14 (d, J = 8.3 Hz, 1H), 7.10 (dd, J = 7.8, 1.6Hz, 1H), 6.98 (dd, J = 7.5, 1.6 Hz, 1H), 6.84 (dd, J = 7.6, 3.7 Hz, 1H), 3.80(d, J = 17.4 Hz, 1H), 2.98 (d, J = 17.4 Hz, 1H), 1.96 (dq, J = 14.4, 7.2 Hz, 1H), 1.39 (dd, J = 14.0, 7.2 Hz, 1H), 1.31 (d, J = 1.8 Hz, 9H), 1.17 (s, 3H), 1.00 (t, J = 7.3 Hz, 3H).13 C NMR(125 MHz, CDCl3) δ 191.5, 166.9, 154.9, 150.4,137.7, 137.3, 137.1, 127.1, 127.0, 126.6, 125.1, 125.0, 124.4, 120.9, 120.6,120.0, 117.6, 80.1, 61.7, 34.7, 30.1, 29.9, 29.7, 29.4, 19.9, 17.7, 8.4,8.3.HRMS (ESI) m / z:[M+H] + calcd for C 24 H 27 O4 + 379.4755; found: 379.4758. Example 10 raw material:

[0049] Product 10: Chemical formula: C 27 H 24 O4 Structural formula:

[0050] Yield: 50% 1 H NMR (500 MHz, CDCl3) δ 7.74 (dd, J = 7.8, 1.7 Hz, 1H), 7.40 – 7.34(m, 1H), 7.26 – 7.22 (m, 2H), 7.21 (dd, J = 7.7, 1.7 Hz, 1H), 7.15 (dd, J =7.6, 1.5 Hz, 1H), 7.13 – 7.03 (m, 4H), 6.99 (t, J = 7.6 Hz, 1H), 6.74 (dd, J =8.3, 1.0 Hz, 1H), 5.02 (s, 1H), 4.15 (dt, J = 17.1, 1.0 Hz, 1H), 3.15 (d, J =17.1 Hz, 1H), 1.37 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.5, 165.7, 154.6,152.9, 137.9, 137.0, 134.3, 129.1, 128.1, 127.0, 126.8, 126.7, 124.4, 124.3,121.5, 120.8, 119.0, 117.2, 82.5, 60.5, 34.7, 31.2, 29.8.HRMS (ESI) m / z:[M+H] + calcd for C 27 H 25 O4 + 413.4925; found: 413.4928. Example 11 raw material:

[0051] Product 11: Chemical formula: C 24 H 18 O4 Structural formula:

[0052] Yield: 41% 1 H NMR (500 MHz, CDCl3) δ 7.76 (dd, J = 7.9, 1.7 Hz, 1H), 7.41 – 7.35(m, 1H), 7.23 (dd, J = 6.7, 2.9 Hz, 2H), 7.15 – 7.00 (m, 6H), 6.93 (t, J = 7.5Hz, 1H), 6.74 (dd, J = 8.3, 1.0 Hz, 1H), 5.06 (s, 1H), 4.10 (d, J = 17.0 Hz, 1H), 3.13 (d, J = 17.0 Hz, 1H), 2.25 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 189.7,154.6, 152.1, 137.0, 129.1, 128.4, 128.0, 126.8, 126.7, 126.3, 125.9, 124.5,121.3, 119.7, 118.9, 117.2, 82.2, 60.2, 31.3, 15.8.HRMS (ESI) m / z:[M+H] + calcdfor C 24 H 19 O4 + 371.4115; found: 371.4118. Example 12 raw material:

[0053] Product 12: Chemical formula: C 23 H 20 O4 Structural formula:

[0054] Yield: 61% 1 H NMR (500 MHz, CDCl3) δ 7.53 (d, J = 2.2 Hz, 1H), 7.26 – 7.23 (m, 2H), 7.22 – 7.12 (m, 3H), 7.09 (dd, J = 5.0, 1.9 Hz, 3H), 6.98 (t, J = 7.6 Hz, 1H), 6.64 (d, J = 8.4 Hz, 1H), 5.02 (s, 1H), 4.12 (d, J = 17.0 Hz, 1H), 3.14 (d, J =17.1 Hz, 1H), 2.28 (s, 3H), 1.37 (s, 9H). 13C NMR (125 MHz, CDCl3) δ 191.7,165.9, 153.0, 152.8, 137.9, 134.4, 134.3, 129.0, 128.0, 127.0, 126.7, 126.4,124.3, 121.4, 120.8, 118.6, 116.9, 82.5, 60.3, 34.7, 31.4, 29.8, 20.5.HRMS(ESI) m / z:[M+H] + calcd for C 28 H 27 O4 + 427.5195; found: 427.5199. Example 13 raw material:

[0055] Product 13: Chemical formula: C 27 H 23 ClO4 Structural formula:

[0056] Yield: 46% 1 H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 2.6 Hz, 1H), 7.31 (dd, J = 8.7,2.6 Hz, 1H), 7.25 – 7.19 (m, 3H), 7.17 – 7.10 (m, 4H), 6.99 (t, J = 7.7 Hz, 1H), 6.70 (d, J = 8.7 Hz, 1H), 5.00 (s, 1H), 4.14 (d, J = 17.1 Hz, 1H), 3.14(d, J = 17.1 Hz, 1H), 1.36 (s, 9H). 13C NMR(125 MHz, CDCl3) δ 190.6, 165.1,153.0, 152.9, 138.0, 136.6, 134.1, 130.1, 129.3, 128.2, 127.0, 126.7, 126.1,124.4, 121.6, 120.5, 119.9, 118.8, 82.6, 60.6, 34.7, 31.2, 29.8.HRMS (ESI) m / z:[M+H] + calcd for C 27 H 24 ClO4 + 447.9345; found: 447.9348. Example 14 raw material:

[0057] Product 14: Chemical formula: C 27 H 23 BrO4 Structural formula:

[0058] Yield: 52% 1 H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 2.4 Hz, 1H), 7.44 (dd, J = 8.7,2.5 Hz, 1H), 7.25 – 7.16 (m, 3H), 7.17 – 7.06 (m, 4H), 6.98 (t, J = 7.7 Hz, 1H), 6.63 (d, J = 8.7 Hz, 1H), 5.00 (s, 1H), 4.13 (d, J = 17.0 Hz, 1H), 3.14(d, J = 17.1 Hz, 1H), 1.35 (s, 9H). 13C NMR(125 MHz, CDCl3) δ 190.5, 165.0,153.5, 152.8, 139.5, 138.0, 134.1, 129.4, 129.2, 128.2, 127.0, 126.7, 124.4,121.6, 120.5, 120.3, 119.1, 117.3, 82.6, 60.6, 34.7, 31.2, 29.8.HRMS (ESI) m / z:[M+H] + calcd for C 27 H 24 BrO4 + 492.3885; found: 492.3888. Example 15 raw material:

[0059] Product 15: Chemical formula: C 28 H 26 O5 Structural formula:

[0060] Yield: 49% 1 H NMR (500 MHz, CDCl3) δ 7.69 (d, J = 8.8 Hz, 1H), 7.25 (dd, J = 3.3, 2.0 Hz, 2H), 7.20 (dd, J = 7.8, 1.6 Hz, 1H), 7.15 – 7.09 (m, 4H), 6.97 (t, J =7.7 Hz, 1H), 6.60 (dd, J = 8.8, 2.4 Hz, 1H), 6.16 (d, J = 2.3 Hz, 1H), 5.04 (s,1H), 4.13 (d, J = 17.0 Hz, 1H), 3.76 (s, 3H), 3.12 (d, J = 17.1 Hz, 1H), 1.36 (s, 9H). 13C NMR(125 MHz, CDCl3) δ 189.6, 166.6, 166.0, 156.6, 153.0, 137.9,134.6, 128.9, 128.7, 128.0, 127.0, 126.8, 124.2, 121.4, 120.9, 112.9, 112.3,100.6, 82.3, 59.7, 55.9, 34.7, 31.4, 29.9.HRMS (ESI) m / z:[M+H] + calcd forC 28 H 27 O5 + 443.5185; found: 443.5188. Example 16 raw material:

[0061] Product 16: Chemical formula: C 27 H 23 BrO4 Structural formula:

[0062] Yield: 49% 1 H NMR (500 MHz, CDCl3) δ 7.59 (d, J = 8.4 Hz, 1H), 7.21 (td, J = 8.4, 1.7 Hz, 4H), 7.13 (td, J = 7.3, 2.1 Hz, 4H), 6.99 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 1.8 Hz, 1H), 5.00 (s, 1H), 4.14 (d, J = 17.1 Hz, 1H), 3.14 (d, J = 17.1 Hz, 1H), 1.36 (s, 9H). 13C NMR(125 MHz, CDCl3) δ 190.6, 165.0, 154.6, 152.9, 138.0,134.1, 131.3, 129.3, 128.2, 128.0, 127.9, 127.0, 126.7, 124.4, 121.6, 120.6,120.4, 117.9, 82.6, 60.7, 34.7, 31.2, 29.8.HRMS (ESI) m / z:[M+H] + calcd forC 27 H 24 BrO4 + 492.3885; found: 492.3888. Example 17 raw material:

[0063] Product 17: Chemical formula: C 28 H 27 O4 Structural formula:

[0064] Yield: 52% 1 H NMR (500 MHz, CDCl3) δ 7.73 (dd, J = 7.8, 1.7 Hz, 1H), 7.41 – 7.35(m, 1H), 7.20 (dd, J = 7.9, 1.7 Hz, 1H), 7.16 – 7.09 (m, 3H), 7.07 (td, J =7.6, 1.0 Hz, 1H), 6.98 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 7.8 Hz, 2H), 6.74 (dd, J = 8.3, 1.0 Hz, 1H), 4.99 (s, 1H), 4.19 – 4.08 (m, 1H), 3.14 (d, J = 17.1 Hz,1H), 2.14 (s, 3H), 1.36 (s, 9H). 13C NMR(100 MHz, CDCl3) δ 191.6, 165.8, 154.6,153.0, 138.9, 137.9, 136.7, 131.3, 128.6, 127.0, 126.8, 126.7, 126.6, 124.4,124.3, 121.4, 120.8, 119.0, 117.2, 82.5, 60.6, 34.7, 31.2, 29.8, 21.0.HRMS(ESI) m / z:[M+H] + calcd for C 28 H 27 O4 + 427.5195; found: 427.5199. Example 18 raw material:

[0065] Product 18: Chemical formula: C 27 H 23 BrO4 Structural formula:

[0066] Yield: 41% 1 H NMR (500 MHz, CDCl3) δ 7.75 (dd, J = 7.8, 1.7 Hz, 1H), 7.49 – 7.44(m, 1H), 7.21 (td, J = 7.7, 7.1, 1.7 Hz, 3H), 7.18 – 7.04 (m, 4H), 6.98 (t, J =7.6 Hz, 1H), 6.79 (dd, J = 8.3, 0.9 Hz, 1H), 4.99 (s, 1H), 4.11 (d, J = 17.0Hz, 1H), 3.15 (d, J = 17.1 Hz, 1H), 1.35 (s, 9H). 13C NMR(100 MHz, CDCl3) δ168.1, 144.6, 143.5, 139.9, 136.4, 134.3, 131.1, 130.4, 128.7, 127.5, 127.3,126.7, 123.5, 121.9, 108.0, 107.3, 99.4, 61.0, 49.7, 48.6, 43.8, 27.8,24.7.HRMS (ESI) m / z:[M+H] + calcd for C 27 H 24 BrO4 + 492.3885; found: 492.3886. Example 19 raw material:

[0067] Product 19: Chemical formula: C 28 H 26 O5 Structural formula:

[0068] Yield: 46% 1 H NMR (500 MHz, CDCl3) δ 7.75 (dd, J = 7.9, 1.8 Hz, 1H), 7.42 – 7.38(m, 1H), 7.20 (dd, J = 7.8, 1.6 Hz, 1H), 7.17 – 7.12 (m, 1H), 7.11 – 7.06 (m,1H), 6.97 (td, J = 8.0, 6.4 Hz, 2H), 6.82 – 6.76 (m, 3H), 6.57 – 6.61 (m, 1H), 4.99 (s, 1H), 4.14 (dt, J = 16.9, 1.0 Hz, 1H), 3.77 (s, 1H), 3.67 (s, 3H), 3.14 (d, J = 17.0 Hz, 1H), 1.47 (s, 2H), 1.37 (s, 9H). 13C NMR(100 MHz, CDCl3) δ189.8, 168.5, 159.0, 153.6, 152.9, 137.7, 137.0, 136.3, 135.6, 129.2, 129.0,127.0, 126.8, 126.1, 124.8, 124.4, 124.3, 121.5, 120.9, 120.7, 119.2, 119.1,117.2, 116.8, 115.4, 111.6, 111.5, 82.6, 82.4, 60.4, 60.3, 55.2, 55.1, 34.7,34.7, 32.1, 31.3, 29.8, 29.7.HRMS (ESI) m / z:[M+H] + calcd forC 28 H 27 O5 + 443.5185; found: 443.5188. Example 20 raw material:

[0069] Product 20: Chemical formula: C 31 H 26 O4 Structural formula:

[0070] Yield: 41% 1 H NMR (500 MHz, CDCl3) δ 7.73 – 7.61 (m, 4H), 7.58 (d, J = 8.6 Hz, 1H),7.45 – 7.35 (m, 3H), 7.24 – 7.15 (m, 2H), 7.04 – 6.98 (m, 1H), 7.01 (t, J =7.7 Hz, 1H), 6.85 (td, J = 7.6, 1.0 Hz, 1H), 6.52 (dd, J = 8.4, 1.0 Hz, 1H),5.19 (s, 1H), 4.21 (dt, J = 17.1, 1.1 Hz, 1H), 3.19 (d, J = 17.1 Hz, 1H), 1.38 (s, 9H). 13C NMR(100 MHz, CDCl3) δ 191.5, 165.8, 154.4, 153.0, 138.0, 136.6,133.3, 132.3, 131.8, 128.1, 128.0, 127.4, 127.1, 126.6, 126.6, 126.5, 126.2,124.4, 124.3, 123.8, 121.6, 120.8, 118.9, 116.9, 82.7, 60.5, 34.7, 31.3,29.9.HRMS (ESI) m / z:[M+H] + calcd for C 31 H 27 O4 + 463.5525; found: 463.5528. Example 21 raw material:

[0071] Product 21: Chemical formula: C 46 H 39 NO7 Structural formula:

[0072] Yield: 53% 1 H NMR (500 MHz, CDCl3) δ 7.71 (dd, J = 7.8, 1.7 Hz, 1H), 7.68 – 7.63(m, 2H), 7.62 – 7.57 (m, 2H), 7.44 – 7.29 (m, 7H), 7.23 – 7.18 (m, 3H), 7.15(dd, J = 7.5, 1.5 Hz, 1H), 7.08 – 7.02 (m, 3H), 6.99 (t, J = 7.6 Hz, 1H), 6.71(dd, J = 8.4, 1.0 Hz, 1H), 4.99 (d, J = 18.5 Hz, 3H), 4.14 (d, J = 17.0 Hz, 1H), 3.26 – 3.11 (m, 3H), 2.95 (dd, J = 8.0, 6.8 Hz, 2H), 1.37 (s, 9H). 13C NMR(125MHz, CDCl3) δ 191.3, 171.6, 165.6 161.6, 154.5, 152.9, 145.6, 137.9, 137.0,136.8, 135.2, 134.3, 132.4, 129.0, 128.7, 128.7, 128.6, 128.2, 127.9, 127.5,127.1, 127.0, 126.8, 126.5, 124.5, 124.3, 121.6, 120.8, 119.0, 117.1, 82.2,65.7, 60.5, 34.7, 31.2, 31.1, 29.9, 29.7, 23.5.HRMS (ESI) m / z:[M+H] + calcd forC 46 H 40 NO7 + 718.8255; found: 718.8254. Example 22 raw material:

[0073] Product 22: Chemical formula: C 42 H 35 Cl2NO6 Structural formula:

[0074] Yield: 65% 1 H NMR (500 MHz, CDCl3) δ 7.70 (dd, J = 7.9, 1.7 Hz, 1H), 7.35 (s, 1H), 7.33 (s, 1H), 7.31 – 7.25 (m, 1H), 7.21 (qd, J = 7.1, 1.6 Hz, 4H), 7.15 (td, J = 7.8, 1.7 Hz, 2H), 7.03 (d, J = 8.1 Hz, 2H), 6.99 (td, J = 7.8, 4.7 Hz, 4H), 6.87 (s, 1H), 6.63 (dd, J = 8.3, 1.0 Hz, 1H), 6.57 (d, J = 8.0 Hz, 1H), 5.07 –4.88 (m, 3H), 4.13 (d,J = 17.1 Hz, 1H), 3.82 (s, 2H), 3.14 (d, J = 17.1 Hz, 1H), 1.36 (s, 9H). 13 C NMR(125 MHz, CDCl3) δ 191.30, 171.9, 165.6, 154.5,152.8, 142.7, 137.9, 137.7, 137.1, 136.6, 134.4, 130.9, 129.5, 128.9, 128.2,127.6, 127.1, 127.0, 126.8, 124.5, 124.3, 124.1, 122.2, 121.6, 120.8, 119.0,118.4, 117.1, 82.2, 66.1, 60.5, 38.6, 34.7, 31.1, 29.9.HRMS (ESI) m / z:[M+H] + calcd for C 42 H 36 Cl2NO6 + 721.6505; found: 721.6508. Most of the compounds in this invention exhibit an inhibition rate of over 90% against Fusarium graminearum at a concentration of 50 mg / L. These compounds demonstrate good inhibitory effects against Fusarium graminearum, thus showing promising application prospects in the prevention and control of wheat stem rot.

[0075] Herbicide test results: The compounds of this invention showed inhibition rates against Fusarium graminearum, respectively.

[0076] Note: "++++" indicates an inhibition rate of 90%-100% at a concentration of 50 mg / L; "++++" indicates an inhibition rate of 70%-90% at a concentration of 50 mg / L; "+++" indicates an inhibition rate of 50%-70% at a concentration of 50 mg / L; "++" indicates an inhibition rate of 30%-50% at a concentration of 50 mg / L; and "+" indicates an inhibition rate of 10%-30% at a concentration of 50 mg / L.

[0077] 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 principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A two-color full-frame spiral ring, characterized in that, Its structural formula is shown in Equation 1: In Equation 1, R 1 It is any one of hydrogen, fluorine, chlorine, bromine, methyl, and methoxy; R 2 R is either methyl or tert-butyl. 3 It is any one of phenyl, p-methylphenyl, p-bromophenyl, 3-methoxyphenyl, naphthyl, oxapzin derivatives, and diclofenac derivatives; R 4 R is any one of hydrogen atom and methyl group. 1 R 2 R 3 R 4 Whether they are the same or different, each represents a substituent independently.

2. The method for synthesizing a spirotoroidal bicolor full skeleton according to claim 1, characterized in that, Includes the following steps: 4-hydroxycoumarin and salicylaldehyde derivatives were mixed evenly in a solvent and reacted under alkaline conditions at 100–120 °C to prepare a spirocyclic bicolor full-skeletal compound. The structural formula of the above-mentioned 4-hydroxycoumarin is shown in Formula 2: In Equation 2, R 1 It can be any one of hydrogen atom, fluorine, chlorine, methyl, or methoxy. The structural formula of the above-mentioned salicylaldehyde derivative is shown in Formula 3: In Equation 3, R 2 It is either methyl or tert-butyl; R 3 It is any one of phenyl, p-methylphenyl, p-bromophenyl, 3-methoxyphenyl, naphthyl, oxapzin derivatives, and diclofenac derivatives; R 4 It can be any one of hydrogen atom or methyl group.

3. The synthesis method according to claim 2, characterized in that, The solvent is 1,2-dichloroethane, dichloromethane, toluene, or tetrahydrofuran.

4. The synthesis method according to claim 2, characterized in that, The amount of solvent used is 10-25 L per mole of 4-hydroxycoumarin and salicylaldehyde derivative.

5. The synthesis method according to claim 2, characterized in that, The amount of catalyst used is 50–200 mol.

6. The application of the spirocyclic bicolor bioactive framework of claim 1 in Fusarium species, characterized in that, Application in the prevention and control of wheat stem base rot.

7. A bactericide, characterized in that, Its active ingredient is one or more of the spirocyclic bicolor full-skeletal compounds described in claim 1.

8. The bactericide according to claim 6, characterized in that, The fungicide also includes pesticide-acceptable adjuvants, additives, stabilizers, fragrances, emulsifiers, or synergists.

Images