A pleuromutilin derivative containing long chain quaternary ammonium salt side chain and its preparation method and application

Abstract

This invention discloses a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, its preparation method, and its applications, belonging to the field of medicinal chemistry. The invention provides a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain. Using truncated pleurotin as the parent nucleus, its structure was modified, and extensive bioactivity screening was conducted to synthesize a novel truncated pleurotin quaternary ammonium salt antibiotic with antimicrobial activity. In vitro antibacterial activity experiments demonstrated that the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain synthesized in this invention has excellent antimicrobial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA).

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry technology, and in particular relates to a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, its preparation method and application. Background Technology

[0002] With the long-term and extensive use of antibiotics in clinical practice and animal husbandry, the problem of bacterial resistance has become increasingly serious. The efficacy of many commonly used antimicrobial drugs continues to decline, and multidrug-resistant and even pan-drug-resistant strains are constantly emerging, becoming a significant factor threatening public health and the sustainable development of the livestock industry. Most existing antimicrobial drugs exert their effects by inhibiting traditional targets such as bacterial cell wall synthesis, protein synthesis, or nucleic acid metabolism, resulting in relatively simple mechanisms of action and a tendency to induce antibiotic resistance in bacteria with long-term use. Therefore, the development of novel, safe, and effective antimicrobial drugs that target new targets and are less likely to induce bacterial resistance is urgently needed. Summary of the Invention

[0003] To address the aforementioned problems, this invention provides a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, its preparation method, and its applications. The truncated pleurotin derivative provided by this invention exhibits a novel cell membrane-targeting antibacterial mechanism, good antibacterial activity, and low toxicity, making it suitable as a novel antibacterial drug for systemic infections in animals or humans.

[0004] To achieve the above-mentioned objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, the general chemical formula of which is: , Where n = 0, 1, 2, 3 or 4; m = 1, 3, 5 or 7.

[0005] Furthermore, its chemical structural formula includes: .

[0006] Pleuroromutilin is a tricyclic diterpenoid compound isolated in 1951 from the fermentation broth of the fungus *Pleurotus Mutilus (Fr.) Sacc. Drosophila Subatrata* and *P. passeckeriamus Pilat* by Kavanagh L.'s team at Columbia University. It exhibits good antibacterial activity against Gram-positive bacteria. Pleuroromutilin binds to the 23S rRNA of the bacterial 50S ribosomal subunit. Its tricyclic nucleus positions it at the peptidyl transferase center (PTC) of the 50S ribosomal subunit, forming a tight pocket at site A. Simultaneously, its C-14 side chain covers the P site where tRNA binds to the ribosome, thereby directly inhibiting peptide bond formation and preventing bacterial protein synthesis. Due to its highly specific binding site, this class of drugs is less prone to cross-resistance with other protein synthesis inhibitors and maintains high activity against multidrug-resistant bacteria. However, with increased clinical application, bacterial resistance to these drugs has gradually emerged. Studies have found that bacteria can develop resistance through high expression of efflux pumps or target mutations. Therefore, structurally modifying the truncated pleurotin nucleus to give it a new mechanism of action is key to solving the resistance problem.

[0007] Secondly, the present invention provides a method for preparing the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, comprising the following steps: S1. Intermediate I was obtained by acylation reaction using truncated pleurotin and p-toluenesulfonyl chloride as raw materials; S2. Using the intermediate I and p-hydroxythiophenol as raw materials, intermediate II is obtained through a nucleophilic substitution reaction under alkaline conditions; S3. Intermediate II reacts with dibromoalkane via a nucleophilic substitution reaction to yield intermediate III; S4. The intermediate III undergoes a quaternization reaction with a tertiary amine to obtain a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain.

[0008] Furthermore, the chemical structural formula of intermediate I is as follows: ; The chemical structural formula of intermediate II is: ; The chemical structural formula of intermediate III is as follows: , where n = 0, 1, 2, 3 or 4.

[0009] Further, in step S1, the acylation reaction is carried out at room temperature, and the molar ratio of truncated pleurotin to p-toluenesulfonyl chloride is 1:1.2; in step S2, the nucleophilic substitution reaction is carried out at 70°C, and the molar ratio of intermediate I to p-hydroxythiophenol is 1:1.5; in step S3, the nucleophilic substitution reaction is carried out at 75°C, and the molar ratio of intermediate II to dibromoalkane is 1:1.5; in step S4, the quaternization reaction is carried out at 90°C, and the molar ratio of intermediate III to tertiary amine is 1:1. In step S1, the solvent used in the reaction is dichloromethane; in step S2, the solvent used in the reaction is ethyl acetate; in step S3, the solvent used in the reaction is acetonitrile or acetone; and in step S4, the solvent used in the reaction is acetonitrile or ethanol.

[0010] This invention provides a simple and efficient four-step reaction process to prepare truncated pleurotin derivatives containing long-chain quaternary ammonium salt side chains. The reactants are inexpensive and readily available, the reaction conditions are mild, and the product yield is high, making it suitable for industrial production.

[0011] Quaternary ammonium salts are a class of compounds formed when the four hydrogen atoms in an ammonium ion are replaced by hydrocarbon groups. In aqueous systems, they can dissociate to form stable quaternary ammonium cations. Since bacterial cell surfaces typically carry a negative charge, quaternary ammonium cations can adsorb onto the cell wall and cell membrane surface through electrostatic interactions, further disrupting the structural integrity of the cell membrane and ultimately causing damage to bacterial protein structure and function, thus achieving bacterial killing. Quaternary ammonium salt compounds exhibit good water solubility and chemical stability, are easy to use, and possess both high bactericidal efficiency and relatively low toxicity, demonstrating broad-spectrum antibacterial properties.

[0012] Thirdly, the present invention provides a pharmaceutically acceptable salt of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, a solvent compound of the acceptable salt, an enantiomer, a diastereomer, and a tautomer, and a mixture of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain in any proportion of a pharmaceutically acceptable salt, a solvent compound of the acceptable salt, an enantiomer, a diastereomer, and a tautomer.

[0013] Fourthly, the present invention provides the use of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, and its pharmaceutically acceptable salt, solvent compound of the acceptable salt, enantiomer, diastereomer and tautomer in the preparation of pharmaceutical formulations for treating bacterial infectious diseases.

[0014] The bacterial infectious diseases mentioned above are diseases caused by infection with pathogenic microorganisms in humans or animals.

[0015] Preliminary bioactivity tests of this invention show that the truncated pleurotin derivatives containing long-chain quaternary ammonium salt side chains provided by this invention have good antibacterial activity, especially against methicillin-resistant Staphylococcus aureus. In vitro erythrocyte hemolytic activity data show that these compounds have low hemolytic toxicity. In summary, these results demonstrate their important value in the development of drugs against drug-resistant bacteria and their potential as novel antibiotics for the treatment of infectious diseases.

[0016] Furthermore, the pharmaceutical preparation for treating bacterial infectious diseases is an oral administration preparation or a non-oral administration preparation; the oral administration preparation includes tablets, capsules, granules, syrups, premixes, or microcapsules; the non-oral administration preparation includes liniments and injections.

[0017] Fifthly, the present invention provides a pharmaceutical composition in which the active ingredient comprises the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain; or comprises a pharmaceutically acceptable salt, a solvent compound of the acceptable salt, an enantiomer, a diastereomer, or a tautomer of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain.

[0018] Compared with the prior art, the present invention has the following advantages and technical effects: This invention provides a truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain. Using truncated pleurotin as the parent nucleus, its structure was modified, and extensive bioactivity screening was conducted to synthesize a novel truncated pleurotin quaternary ammonium salt antibiotic with antimicrobial activity. In vitro antibacterial activity experiments demonstrated that the synthesized truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain exhibits excellent antimicrobial activity, particularly against methicillin-resistant Staphylococcus aureus (MRSA). Specifically, compounds 11, 12, 13, and 14 showed MIC values ​​(minimum inhibitory concentrations) between 0.5 and 4 μg / mL against Staphylococcus aureus (ATCC 29213) and eight clinically isolated MRSA strains, demonstrating significantly superior antimicrobial activity compared to the control drug tiamulin. HC50 (half-maximal hemolytic concentration) results showed that compound 13 exhibited lower hemolytic toxicity and higher selectivity. Cytotoxicity and in vivo toxicity studies further revealed that compound 13 also possessed low toxicity. This indicates that the truncated pleurotin derivative synthesized in this invention can be used to treat infectious diseases in humans or animals, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), demonstrating significant pharmaceutical development value. Furthermore, taking compound 13 as an example, the antibacterial mechanism of this class of compounds was investigated. It was clearly found that these compounds have a bactericidal characteristic targeting the cell membrane and can stimulate bacteria to produce reactive oxygen species, exacerbating membrane damage, leading to leakage of intracellular substances and ultimately bacterial death.

[0019] This invention provides a method for preparing the above-mentioned truncated pleurotin derivative containing long-chain quaternary ammonium salt side chains. The method involves modifying the C-14 side chain of truncated pleurotin with p-hydroxythiophenol and further substituting it with bromoalkane and quaternizing it with tertiary amine to obtain the truncated pleurotin derivative containing long-chain quaternary ammonium salt side chains. This method is safe to operate, low in cost, has a high yield, and mild reaction conditions, making it suitable for industrial production. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0021] Figure 1 The results of in vitro time-based bactericidal kinetics experiments of compound 13 prepared in Example 1 and vancomycin; Figure 2 The results of the cytotoxicity test for compound 13 prepared in Example 1; Figure 3 The results of routine blood tests and blood biochemistry tests were obtained for compound 13 prepared in Example 1 and the control group. Figure 4 Results of in vivo anti-MRSA infection activity assays for the control group, vancomycin (5 mg / kg), and compound 13 (5, 10, and 20 mg / kg); Figure 5 In the image, A and C are MRSA scanning electron microscope images of the blank control group, and B and D are MRSA scanning electron microscope images of the compound 13 treated with it. C is a magnified scanning electron microscope image of A, and D is a magnified scanning electron microscope image of B. Figure 6 The experimental results are for membrane depolarization; Figure 7 In the diagram, A represents the experimental results of DNA leakage, and B represents the experimental results of protein leakage. Figure 8 This is a truncated nucleophilic substitution reaction formula between pleurotin and p-toluenesulfonyl chloride; Figure 9 The reaction formula is the thioetherification reaction between intermediate I and p-hydroxythiophenol; Figure 10 The reaction formula is for the alkylation of intermediate II with dibromoalkane; Figure 11 The reaction formula for preparing truncated pleurotin derivatives containing long-chain quaternary ammonium salt side chains by reacting intermediate III with tertiary amine. Detailed Implementation

[0022] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0023] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0024] The room temperature in this invention refers to 25±2℃.

[0025] Unless otherwise specified, all raw materials and reagents used in this invention are commercially available products.

[0026] Example 1 (1) Preparation of intermediate I: Pleurotus truncated (757 mg, 2 mmol) and p-toluenesulfonyl chloride (TsCl, 456 mg, 2.4 mmol) were dissolved in dichloromethane (DCM, 30 mL), and TEA (triethylamine, 0.8 mL, 6 mmol) and 4-dimethylaminopyridine (DMAP, 24.4 mg, 0.2 mmol) were added. The mixture was stirred at room temperature for 8 h. The reaction was monitored by TLC until complete. The mixture was washed three times with saturated ammonium chloride aqueous solution (50 mL). The organic phase was concentrated and recrystallized from methyl tert-butyl ether to obtain intermediate I (1012.1 mg, 1.9 mmol), with a yield of 95.0%. Figure 8 This is a truncated nucleophilic substitution reaction formula between pleurotin and p-toluenesulfonyl chloride; (2) Preparation of intermediate II: Intermediate I (1 g, 1.9 mmol) was dissolved in 35 mL of ethyl acetate (EA), followed by the addition of sodium iodide (NaI, 0.3 g, 2.0 mmol). The reaction system was stirred at 70 °C for half an hour. Then, p-hydroxythiophenol (0.4 g, 2.8 mmol) dissolved in 20% NaOH aqueous solution was added dropwise. The mixture was stirred at 70 °C until the reaction was complete. The reaction solution was then washed three times with saturated ammonium chloride solution (20 mL), dried, filtered, and concentrated. The crude product was purified by silica gel column chromatography with petroleum ether:ethyl acetate (volume ratio 1:1) as the eluent, and the yield was 80%. Figure 9 The reaction formula is the thioetherification reaction between intermediate I and p-hydroxythiophenol.

[0027] Intermediate II: 1 H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.6 Hz, 2H), 6.73 (d, J =8.6 Hz, 2H), 6.43 (dd, J = 17.4, 11.0 Hz, 1H), 6.17 (s, 1H), 5.70 (d, J = 8.4 Hz, 1H), 5.32 (dd, J= 11.1, 1.5 Hz, 1H), 5.18 (dd, J = 17.4, 1.6 Hz, 1H), 3.43 (d, J =3.5 Hz, 2H), 3.33 (t, J = 8.1 Hz, 1H), 2.31 (p, J = 7.0 Hz, 1H), 2.27 – 2.14 (m,2H), 2.06 (s, 1H), 1.98 (dd, J = 16.1, 8.5 Hz, 1H), 1.88 – 1.69 (m, 2H), 1.68 –1.50 (m, 3H), 1.46 (ddd, J = 13.3, 9.3, 3.4 Hz, 1H), 1.39 (s, 3H), 1.36 – 1.30 (m, 1H), 1.19 – 0.98 (m, 4H), 0.86 (d, J = 7.0 Hz, 3H), 0.65 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.54, 168.81, 156.12, 138.92, 134.26,124.50, 117.28, 116.18, 74.68, 69.36, 58.24, 45.47, 44.65, 43.86, 41.75,39.07, 36.80, 35.96, 34.50, 30.43, 26.81, 26.27, 24.83, 16.72, 14.89, 11.53. Preparation of intermediate III: Intermediate II (0.4 g, 0.8 mmol) was dissolved in 10 mL of acetone, followed by the addition of potassium carbonate (0.3 g, 2.0 mmol) and dibromoalkane (1.2 mmol). The mixture was heated at 75 °C until the reaction was complete. The solvent was evaporated to dryness, and saturated ammonium chloride solution (20 mL) was added. The mixture was then extracted three times with ethyl acetate (25 mL), dried, filtered, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether:ethyl acetate (v / v ratio 2:1) as the eluent. Figure 10 This is the alkylation reaction formula between intermediate II and dibromoalkane.

[0028] The reaction results showed that the yield was 88% when n = 0.

[0029] 1 H NMR (600 MHz, CDCl3) δ 7.36 (d, J = 8.8 Hz, 1H), 6.81 (d, J = 8.8 Hz,1H), 6.42 (dd, J = 17.4, 11.0 Hz, 1H), 5.70 (d, J = 8.5 Hz, 1H), 5.32 (dd, J =11.0, 1.6 Hz, 1H), 5.17 (dd, J = 17.4, 1.7 Hz, 1H), 4.25 (t, J = 6.2 Hz, 1H),3.62 (t, J = 6.2 Hz, 1H), 3.51 – 3.37 (m, 1H), 3.32 (dd, J = 10.1, 6.4 Hz, 1H),2.29 (dq, J = 12.7, 6.4 Hz, 1H), 2.25 – 2.20 (m, 1H), 2.17 (dd, J = 10.7, 8.8 Hz,1H), 2.08 – 2.03 (m, 1H), 1.97 (dd, J = 16.1, 8.6 Hz, 1H), 1.74 (dq, J = 14.6,3.2 Hz, 1H), 1.69 – 1.57 (m, 2H), 1.57 – 1.48 (m, 1H), 1.49 – 1.39 (m, 1H),1.38 (s, 2H), 1.33 (dp, J = 14.4, 3.3 Hz, 1H), 1.20 – 1.03 (m, 3H), 0.85 (d, J =7.0 Hz, 2H), 0.64 (d, J = 7.1 Hz, 2H). 1313C NMR (151 MHz, CDCl3) δ 217.14, 168.45, 157.96, 139.02, 133.78, 125.97, 117.21, 115.41, 74.60, 69.30, 67.91, 58.18, 45.45, 44.69, 43.86, 41.73, 38.80, 36.76, 35.99, 34.48, 30.42, 28.92, 26.83, 26.31, 24.85, 16.74, 14.88, 11.53. When n = 1, the yield is 90%.

[0030] 1 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J J = 8.8 Hz, 2H), 6.79 (d, J J = 8.8 Hz, 2H), 6.40 (dd, J J = 17.4, 11.0 Hz, 1H), 5.68 (d, J J = 8.4 Hz, 1H), 5.30 (dd, J J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J J = 17.5, 1.7 Hz, 1H), 4.05 (t, J J = 5.8 Hz, 2H), 3.57 (t, J J = 6.4 Hz, 2H), 3.47 – 3.35 (m, 2H), 3.30 (dd, J J = 9.9, 6.4 Hz, 1H), 2.28 (p, J J = 6.1 Hz, 3H), 2.23 – 2.09 (m, 2H), 2.04 (s, 1H), 1.95 (dd, J J = 16.1, 8.5 Hz, 1H), 1.72 (dd, J J = 14.4, 3.0 Hz, 1H), 1.68 – 1.54 (m, 2H), 1.49 (dd, J= 13.2, 4.0 Hz, 1H), 1.46 – 1.39 (m, 1H), 1.37 (s, 3H), 1.33 – 1.26 (m, 1H), 1.27 – 1.17 (m, 1H), 1.09 – 1.08 (m, 4H), 0.83 (d, J = 7.0 Hz, 3H), 0.63 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 217.12, 168.52, 158.61, 139.03, 133.83, 125.24, 117.18, 115.20, 74.60, 69.26, 65.35, 58.18, 45.44, 44.67, 43.86, 41.73, 38.92, 36.77, 35.99, 34.48, 32.23, 30.43, 29.92, 26.83, 26.29, 24.85, 16.73, 14.88, 11.53. When n = 2, the yield is 83%.

[0031] 1 H NMR (400 MHz, Chloroform- d ) δ 7.34 (dd, J = 8.6, 3.1 Hz, 2H), 6.80 (dd, J = 8.9, 3.1 Hz, 2H), 6.41 (dd, J = 17.3, 11.0 Hz, 1H), 5.68 (d, J = 8.4 Hz, 1H), 5.29 (dd, J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J = 17.4, 1.6 Hz, 1H), 4.05 (t, J = 5.7 Hz, 2H), 3.57 (t, J = 6.4 Hz, 2H), 3.43 (d, J = 3.6 Hz, 2H), 3.31 (dd, J = 10.5, 6.5 Hz, 1H), 2.28 (p, J= 6.0 Hz, 3H), 2.24 – 2.12 (m, 2H), 2.05 (d, J =2.6 Hz, 1H), 1.95 (dd, J = 16.1, 8.5 Hz, 1H), 1.79 – 1.69 (m, 1H), 1.61 (td, J =11.9, 10.4, 6.5 Hz, 2H), 1.49 (ddt, J = 18.1, 12.4, 6.5 Hz, 3H), 1.37 (s, 3H),1.34 – 1.22 (m, 2H), 1.09 (d, J = 10.9 Hz, 5H), 0.84 (d, J = 7.0 Hz, 3H), 0.63(d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.10, 168.46, 158.58,139.03, 133.87, 125.21, 117.13, 115.18,74.58, 69.25, 65.33, 58.16, 45.43,44.65, 43.85, 41.72, 38.93, 38.89, 36.76, 35.98, 34.47, 32.21, 30.41, 29.95,26.83, 26.32, 24.84, 16.72, 14.88, 11.53. When n = 3, the yield is 70%.

[0032] 1 H NMR (400 MHz, Chloroform- d ) δ 7.35 (d, J = 8.8 Hz, 2H), 6.78 (d, J =8.8 Hz, 2H), 6.42 (dd, J = 17.4, 11.0 Hz, 1H), 5.70 (d, J = 8.4 Hz, 1H), 5.32(dd, J = 11.0, 1.6 Hz, 1H), 5.17 (dd, J = 17.4, 1.6 Hz, 1H), 3.93 (t,J = 6.3 Hz,2H), 3.59 – 3.35 (m, 4H), 3.32 (s, 1H), 2.35 – 2.26 (m, 1H), 2.25 – 2.12 (m,2H), 2.08 – 2.01 (m, 1H), 2.01 – 1.87 (m, 3H), 1.84 – 1.70 (m, 3H), 1.61(dddd, J = 16.0, 10.6, 8.9, 5.2 Hz, 4H), 1.55 – 1.48 (m, 1H), 1.49 – 1.41 (m,1H), 1.38 (s, 3H), 1.35 – 1.29 (m, 1H), 1.22 – 0.99 (m, 5H), 0.85 (d, J = 7.0Hz, 3H), 0.65 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.04,168.49, 158.91, 139.05, 133.89, 124.86, 117.11, 115.16, 74.60, 69.26, 67.66,58.18, 45.44, 44.68, 43.87, 41.73, 38.99, 36.77, 36.00, 34.46, 33.55, 32.43,30.43, 28.35, 26.83, 26.30, 24.84, 24.80, 16.71, 14.87, 11.49. When n = 4, the yield is 80%.

[0033] 1 H NMR (400 MHz, Chloroform- d ) δ 7.34 (d, J = 8.8 Hz, 2H), 6.77 (d, J =8.8 Hz, 2H), 6.41 (dd, J = 17.4, 11.0 Hz, 1H), 5.69 (d, J = 8.4 Hz, 1H), 5.30(dd, J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J= 17.4, 1.7 Hz, 1H), 3.91 (t, J = 6.4 Hz,2H), 3.49 – 3.35 (m, 4H), 3.32 (d, J = 6.9 Hz, 1H), 2.28 (q, J = 5.8, 4.7 Hz,1H), 2.23 – 2.11 (m, 2H), 2.10 – 2.01 (m, 1H), 1.95 (dd, J = 16.1, 8.6 Hz, 1H),1.91 – 1.84 (m, 2H), 1.82 – 1.68 (m, 3H), 1.60 (dtd, J = 13.6, 10.9, 6.4 Hz,2H), 1.54 – 1.42 (m, 6H), 1.37 (s, 3H), 1.34 – 1.27 (m, 1H), 1.17 – 0.99 (m,5H), 0.84 (d, J = 7.0 Hz, 3H), 0.63 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.05, 168.49, 158.99, 139.05, 133.90, 124.74, 117.08,115.16, 74.59, 69.25, 67.80, 58.18, 45.43, 44.67, 43.86, 41.72, 39.00, 36.77,35.99, 34.46, 33.78, 32.64, 30.42, 28.99, 27.87, 26.82, 26.31, 25.26, 24.84,16.69, 14.86, 11.49. (3) Preparation of products 1-20: Intermediate III (1.0 mmol) was dissolved in 3 mL of acetonitrile, tertiary amine (1.0 mmol) was added, the tube was sealed and heated to 90 °C until the reaction was complete, the solvent was evaporated to dryness, and the crude product was purified by silica gel column chromatography with dichloromethane:methanol (volume ratio 10:1) as the eluent to prepare compounds 1-20. Figure 11 A reaction flow diagram for the preparation of truncated pleurotin derivatives containing long-chain quaternary ammonium salt side chains by reacting intermediate III with a tertiary amine.

[0034] Compound 1, yield 85%. 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.8 Hz, 2H),6.83 (d, J = 8.8 Hz, 2H), 6.39 (dd, J = 17.4, 11.0 Hz, 1H), 5.67 (d, J = 8.4 Hz,1H), 5.29 (dd, J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J = 17.4, 1.7 Hz, 1H), 4.59 –4.36 (m, 2H), 4.24 (m, 2H), 3.73 – 3.55 (m, 2H), 3.49 – 3.43 (m, 8H), 3.35(t, J = 8.1 Hz, 1H), 2.32 – 2.12 (m, 3H), 2.07 (s, 1H), 1.98 (dd, J = 16.0, 8.5Hz, 1H), 1.82 (td, J = 10.0, 5.8 Hz, 2H), 1.73 (dd, J = 14.5, 3.0 Hz, 1H), 1.68 –1.56 (m, 3H), 1.54 – 1.37 (m, 4H), 1.35 (s, 3H), 1.31 – 1.27 (m, 1H), 1.14 –1.06 (m, 4H), 1.00 (t, J = 7.4 Hz, 3H), 0.85 (d, J = 7.0 Hz, 3H), 0.64 (d, J = 6.9Hz, 3H). 13 C NMR (101 MHz, Chloroform- d) δ 217.10, 168.24, 156.64, 139.20, 133.61, 127.40, 117.00, 115.09, 74.48, 69.55, 66.07, 62.53, 62.41, 58.15, 52.01, 45.44, 44.75, 43.93, 41.74, 38.50, 36.74, 36.01, 34.48, 30.41, 26.84, 26.58, 24.83, 24.78, 19.67, 16.73, 14.86, 13.72, 11.50. Compound 2, yield 83%. 1 H NMR (400 MHz, CDCl3) δ 7.37 (d, J J = 8.6 Hz, 2H), 6.82(d, J J = 8.6 Hz, 2H), 6.39 (dd, J J = 17.4, 11.0 Hz, 1H), 5.67 (d, J J = 8.4 Hz, 1H), 5.28 (dd, J J = 11.0, 1.6 Hz, 1H), 5.14 (dd, J J = 17.4, 1.7 Hz, 1H), 4.47 - 4.45 (m, 2H), 4.25 (t, J J = 4.5 Hz, 2H), 3.68 – 3.55 (m, 2H), 3.52 – 3.31 (m, 8H), 3.34(t, J J = 8.1 Hz, 1H), 2.29 – 2.09 (m, 3H), 2.06 (s, 1H), 1.96 (dd, J J = 16.0, 8.5Hz, 1H), 1.85 – 1.66 (m, 4H), 1.65 – 1.53 (m, 2H), 1.48 (dd, J J = 13.5, 3.4 Hz, 1H), 1.43 – 1.25 (m, 11H), 1.12 – 0.99 (m, 4H), 0.93 – 0.77 (m, 6H), 0.62 (d, J J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform - d) δ 217.14, 168.22, 156.67,139.25, 133.57, 127.29, 116.93, 115.12, 74.42, 69.56, 66.15, 62.47, 62.41,58.14, 52.04, 45.44, 44.72, 43.93, 41.73, 38.49, 36.73, 36.01, 34.48, 31.27,30.40, 26.83, 26.64, 25.91, 24.82, 22.87, 22.39, 16.71, 14.84, 13.91, 11.51. Compound 3, yield 79%. 1 H NMR (400 MHz, CDCl3) δ 7.37 (d, J J = 8.7 Hz, 2H), 6.82(d, J J = 8.8 Hz, 2H), 6.39 (dd, J J = 17.4, 11.0 Hz, 1H), 5.67 (d, J J = 8.4 Hz, 1H),5.28 (dd, J J = 11.0, 1.6 Hz, 1H), 5.20 – 5.02 (m, 1H), 4.46 (d, J J = 4.2 Hz, 2H),4.25 (d, J J = 4.4 Hz, 2H), 3.69 – 3.55 (m, 2H), 3.57 – 3.28 (m, 8H), 3.34 (s,1H), 2.33 – 2.13 (m, 3H), 2.07 (d, J J = 2.7 Hz, 1H), 1.98 (dd, J J = 16.1, 8.5 Hz,1H), 1.85 – 1.70 (m, 3H), 1.69 – 1.53 (m, 3H), 1.49 (dd, J J = 13.6, 3.4 Hz, 1H),1.46 – 1.39 (m, 1H), 1.39 – 1.32 (m, 7H), 1.32 – 1.24 (m, 7H), 1.13 – 1.04(m, 4H), 0.88 – 0.83 (m, 6H), 0.63 (d, J J = 6.9 Hz, 3H). 1313C NMR (101 MHz, Chloroform- d ) δ 217.09, 168.23, 156.64, 139.21, 133.60, 127.40, 116.99, 115.09, 74.46, 69.55, 66.25, 62.48, 62.41, 58.15, 52.01, 45.44, 44.74, 43.93, 41.73, 38.51, 36.74, 36.01, 34.48, 31.62, 30.40, 29.16, 29.03, 26.84, 26.58, 26.28, 24.83, 22.94, 22.55, 16.73, 14.85, 14.05, 11.49. Compound 4, yield 78%. 1 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J J = 8.8 Hz, 2H), 6.83 (d, J J = 8.8 Hz, 2H), 6.37 (dd, J J = 17.4, 11.0 Hz, 1H), 5.65 (d, J J = 8.4 Hz, 1H), 5.27 (dd, J J = 11.0, 1.6 Hz, 1H), 5.13 (dd, J J = 17.4, 1.6 Hz, 1H), 4.71 (s, 1H), 4.52 – 4.35 (m, 2H), 4.26 – 4.06 (m, 2H), 3.61 – 3.50 (m, 2H), 3.43 – 3.41 (m, 8H), 3.35 (t, J J = 8.1 Hz, 1H), 2.31 – 2.10 (m, 3H), 2.08 (d, J J = 2.8 Hz, 1H), 1.97 (dd, J J = 16.0, 8.5 Hz, 1H), 1.85 – 1.66 (m, 4H), 1.65 – 1.52 (m, 2H), 1.52 – 1.45 (m, 1H), 1.44 – 1.39 (m, 1H), 1.38 – 1.30 (m, 8H), 1.30 – 1.21 (m, 10H), 1.15 – 1.02 (m, 4H), 0.8(td, J= 6.9, 2.5 Hz, 6H), 0.63 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.23, 168.24, 156.71, 139.23, 133.62, 127.21, 116.96, 115.14, 74.43, 69.58, 66.15, 62.55, 62.42, 58.14, 52.12, 45.44, 44.71, 43.94, 43.23, 41.73, 38.48, 36.75, 36.00, 34.49, 31.82, 30.40, 29.42, 29.40, 29.22, 26.84, 26.62, 26.29, 24.82, 22.93, 22.64, 16.71, 14.85, 14.10, 11.49. Compound 5, yield 81%. 1 H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 6.39 (dd, J = 17.4, 11.0 Hz, 1H), 5.66 (d, J = 8.4 Hz, 1H), 5.29 (dd, J = 11.0, 1.6 Hz, 1H), 5.14 (dd, J = 17.4, 1.6 Hz, 1H), 4.07 (t, J = 5.� Hz, 2H), 3.83 – 3.68 (m, 2H), 3.60 – 3.50 (m, 2H), 3.45 – 3.37 (m, 8H), 3.36 – 3.31 (m, 1H), 2.33 – 2.09 (m, 5H), 2.06 (s, 1H), 1.95 (dd, J = 16.0, 8.5 Hz, 1H), 1.77 – 1.63 (m, 4H), 1.63 – 1.53 (m, 2H), 1.50 – 1.36 (m, 4H), 1.34 (s, 3H), 1.23 (s, 1H), 1.11 (s, 3H), 1.07 (d,J = 4.1 Hz, 1H), 0.98 (t, J = 7.3 Hz, 3H), 0.84 (d, J = 7.0 Hz, 3H), 0.62 (d, J = 6.9 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ217.38, 168.35, 157.89, 139.26, 133.67, 125.93, 116.91, 115.16, 74.35, 69.49,64.25, 64.22, 61.28, 58.15, 51.51, 45.44, 44.63, 43.90, 41.70, 38.69, 36.72,35.99, 34.51, 30.39, 26.67, 26.18, 24.81, 24.58, 23.15, 19.93, 16.69, 14.84, 13.75, 11.55. Compound 6, yield 87%. 1 H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.7 Hz, 2H), 6.79(d, J = 8.8 Hz, 2H), 6.39 (dd, J = 17.4, 11.0 Hz, 1H), 5.65 (d, J = 8.4 Hz, 1H), 5.29 (dd, J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J = 17.4, 1.7 Hz, 1H), 4.09 (t, J = 5.4Hz, 2H), 3.83 – 3.67 (m, 2H), 3.57 – 3.47 (m, 2H), 3.40 (q, J = 8.1 Hz, 9H), 2.34 – 2.01 (m, 6H), 1.96 (dd, J = 16.0, 8.5 Hz, 1H), 1.84 (s, 1H), 1.78 – 1.67(m, 3H), 1.66 – 1.55 (m, 3H), 1.48 (dd, J= 13.5, 3.3 Hz, 1H), 1.44 – 1.24 (m,11H), 1.11 (s, 3H), 0.86 (dd, J = 18.2, 6.9 Hz, 6H), 0.62 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.28, 168.37, 157.87, 139.19, 133.73, 126.03,117.06, 115.22, 74.41, 69.47, 64.67, 64.13, 61.45, 58.16, 51.81, 45.45,44.64, 43.93, 41.72, 38.72, 36.75, 35.99, 34.52, 31.26, 30.43, 26.84, 26.58,25.80, 24.82, 23.30, 22.70, 22.40, 16.74, 14.86, 13.95, 11.55. Compound 7, yield 80%. 1 H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.7 Hz, 2H), 6.79(d, J = 8.8 Hz, 2H), 6.39 (dd, J = 17.4, 11.0 Hz, 1H), 5.65 (d, J = 8.4 Hz, 1H),5.29 (dd, J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J = 17.4, 1.6 Hz, 1H), 4.09 (t, J = 5.5Hz, 2H), 3.88 – 3.72 (m, 2H), 3.61 – 3.47 (m, 2H), 3.48 – 3.27 (m, 9H), 2.32– 2.07 (m, 6H), 1.96 (dd, J = 16.1, 8.5 Hz, 1H), 1.78 – 1.69 (m, 3H), 1.68 –1.51 (m, 3H), 1.48 (dd, J= 13.5, 3.4 Hz, 1H), 1.45 – 1.29 (m, 10H), 1.29 –1.23 (m, 6H), 1.12 (s, 3H), 0.91 – 0.78 (m, 6H), 0.63 (d, J = 6.8 Hz, 3H). 13 CNMR (101 MHz, Chloroform- d ) δ 217.27, 168.37, 157.86, 139.18, 133.73, 126.05,117.07, 115.22, 74.41, 69.47, 64.68, 64.12, 61.46, 58.16, 51.81, 45.45,44.64, 43.93, 41.72, 38.72, 36.76, 35.99, 34.52, 31.64, 30.43, 29.18, 29.04,26.84, 26.57, 26.17, 24.82, 23.31, 22.77, 22.59, 16.75, 14.86, 14.10, 11.54. Compound 8, yield 78%. 1 H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.2 Hz, 2H), 6.75 (d, J = 8.3 Hz, 2H), 6.34 (dd, J = 17.3, 11.0 Hz, 1H), 5.62 (d, J = 8.4 Hz, 1H), 5.24 (d, J = 10.9 Hz, 1H), 5.11 (d, J = 17.4 Hz, 1H), 4.04 (t, J = 5.4 Hz, 2H),3.74 – 3.68 (m, 2H), 3.50 – 3.44 (m, 2H), 3.43 – 2.95 (m, 9H), 2.28 – 2.09(m, 5H), 2.04 (s, 1H), 1.92 (dd, J= 16.1, 8.4 Hz, 1H), 1.75 – 1.63 (m, 3H), 1.63 – 1.42 (m, 3H), 1.40 – 1.27 (m, 9H), 1.27 – 1.19 (m, 10H), 1.11 – 1.02(m, 5H), 0.85 – 0.76 (m, 6H), 0.59 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.16, 168.27, 157.86, 139.27, 133.63, 126.03, 116.87,115.17, 74.35, 69.49, 64.29, 61.14, 58.14, 51.49, 45.42, 44.67, 43.92, 41.70,38.68, 36.72, 36.00, 34.47, 31.79, 30.39, 29.64, 29.39, 29.35, 29.20, 26.82,26.67, 26.22, 24.81, 23.16, 22.71, 22.61, 16.67, 14.83, 14.08, 11.50. Compound 9, yield 75%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.32 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 6.36 (dd, J = 17.4, 11.0 Hz, 1H), 5.64 (d, J = 8.4Hz, 1H), 5.26 (dd, J = 11.0, 1.6 Hz, 1H), 5.12 (dd, J = 17.4, 1.7 Hz, 1H), 3.98(t, J = 5.3 Hz, 2H), 3.65 (dd, J = 10.8, 5.4 Hz,2H), 3.54 – 3.44 (m, 2H), 3.40(d, J= 6.2 Hz, 2H), 3.38 – 3.29 (m, 7H), 2.33 – 2.20 (m, 2H), 2.21 – 2.09 (m,1H), 2.09 – 2.02 (m, 1H), 1.91 (tt, J = 12.4, 7.5 Hz, 4H), 1.79 – 1.64 (m, 4H),1.62 – 1.43 (m, 3H), 1.46 – 1.34 (m, 3H), 1.33 – 1.26 (m, 4H), 1.17 – 1.03(m, 5H), 0.95 (t, J = 7.3 Hz, 3H), 0.83 (d, J = 7.0 Hz, 3H), 0.61 (d, J = 6.8 Hz,3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.31, 168.39, 158.38, 139.25, 133.82,125.42, 116.93, 115.12, 74.38, 69.42, 66.72, 63.90, 63.46, 58.17, 51.23,45.45, 44.65, 43.91, 41.71, 38.82, 36.75, 36.01, 34.51, 30.41, 26.82, 26.61,25.83, 24.83, 24.62, 19.79, 19.62, 16.70, 14.84, 13.73, 11.56. Compound 10, yield 81%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.31 (d, J = 8.7 Hz,2H), 6.76 (d, J = 8.8 Hz, 2H), 6.35 (dd, J = 17.4, 11.0 Hz, 1H), 5.63 (d, J = 8.4Hz, 1H), 5.25 (dd, J = 11.0, 1.6 Hz, 1H), 5.11 (dd, J = 17.5, 1.7 Hz, 1H), 3.97(t, J= 5.4 Hz, 2H), 3.77 – 3.57 (m, 2H), 3.49 – 3.42 (m, 2H), 3.39 (d, J = 6.2Hz, 2H), 3.36 – 3.27 (m, 7H), 2.24 (p, J = 4.9 Hz, 2H), 2.18 – 2.08 (m, 1H), 2.04 (d, J = 2.6 Hz, 1H), 1.89 (tt, J = 12.0, 7.4 Hz, 4H), 1.76 (d, J = 9.9 Hz, 1H), 1.66 (dddd, J = 19.7, 15.1, 11.1, 2.6 Hz, 4H), 1.56 – 1.38 (m, 2H), 1.38 –1.21 (m, 11H), 1.16 – 0.98 (m, 5H), 0.91 – 0.74 (m, 6H), 0.60 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.31, 168.37, 158.37, 139.26, 133.81,125.40, 116.90, 115.11, 74.36, 69.42, 66.72, 64.06, 63.41, 58.16, 51.23,45.44, 44.65, 43.91, 41.70, 38.82, 36.74, 36.00, 34.51, 31.23, 30.40, 26.81,26.63, 25.89, 25.82, 24.82, 22.69, 22.39, 19.79, 16.69, 14.84, 13.92, 11.55. Compound 11, yield 86%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.34 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 6.39 (dd, J = 17.4, 11.0 Hz, 1H), 5.66 (d, J= 8.4 Hz, 1H), 5.29 (dd, J = 11.0, 1.6 Hz, 1H), 5.15 (dd, J = 17.4, 1.7 Hz, 1H), 4.00 (t, J = 5.2 Hz, 2H), 3.69 (t, J = 8.0 Hz, 2H), 3.54 – 3.25 (m, 11H), 2.34 – 2.11 (m, 3H), 2.12 – 2.01 (m, 1H), 2.04 – 1.87 (m, 6H), 1.79 – 1.54 (m, 6H), 1.55 – 1.45 (m, 1H), 1.48 – 1.39 (m, 1H), 1.37 – 1.19 (m, 12H), 1.19 – 0.99 (m, 5H), 0.92 – 0.78 (m, 6H), 0.63 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform - d ) δ 217.26, 168.40, 158.37, 139.21, 133.84, 125.51, 117.00, 115.12, 74.44, 69.41, 66.71, 64.10, 63.45, 58.18, 51.25, 45.46, 44.68, 43.92, 41.72, 38.84, 36.77, 36.01, 34.51, 31.62, 30.41, 29.15, 29.03, 26.83, 26.54, 26.27, 25.84, 24.84, 22.79, 22.57, 19.83, 16.72, 14.85, 14.08, 11.53. Compound 12, yield 82%. 1 H NMR (400 MHz, Chloroform - d ) δ 7.33 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 8.7 Hz, 2H), 6.37 (dd, J = 17.4, 11.0 Hz, 1H), 5.65 (d, J = 8.4 Hz, 1H), 5.27 (dd, J= 11.0, 1.6 Hz, 1H), 5.13 (dd, J = 17.4, 1.6 Hz, 1H), 3.98(t, J = 5.2 Hz, 2H), 3.66 (dd, J = 10.7, 5.3 Hz, 2H), 3.52 – 3.23 (m, 11H), 2.24(dt, J = 10.7, 6.2 Hz, 2H), 2.18 – 2.09 (m, 1H), 2.05 (d, J = 2.6 Hz, 1H), 1.98 –1.85 (m, 4H), 1.76 – 1.63 (m, 4H), 1.62 – 1.51 (m, 2H), 1.50 – 1.37 (m, 2H), 1.39 – 1.14 (m, 18H), 1.15 – 0.99 (m, 5H), 0.94 – 0.75 (m, 6H), 0.61 (d, J =6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.27, 168.38, 158.38, 139.24,133.82, 125.46, 116.95, 115.12, 74.40, 69.42, 66.73, 64.07, 63.44, 58.17,51.24, 45.45, 44.66, 43.92, 41.71, 38.82, 36.76, 36.00, 34.51, 31.82, 30.41,29.41, 29.38, 29.23, 29.20, 26.83, 26.58, 26.27, 25.84, 24.83, 22.79, 22.65, 19.81, 16.71, 14.84, 14.12, 11.54. Compound 13, yield 77%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.32 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 6.34 (dd, J = 17.4, 11.0 Hz, 1H), 5.63 (d,J = 8.4Hz, 1H), 5.25 (dd, J = 11.0, 1.6 Hz, 1H), 5.11 (dd, J = 17.4, 1.6 Hz, 1H), 3.91(t, J = 6.0 Hz, 2H), 3.59 – 3.45 (m, 4H), 3.40 (d, J = 7.1 Hz, 2H), 3.37 – 3.28(m, 7H), 2.30 – 2.19 (m, 1H), 2.20 – 2.08 (m, 2H), 2.04 (s, 1H), 1.91 (dd, J =16.0, 8.5 Hz, 1H), 1.88 – 1.74 (m, 5H), 1.75 – 1.61 (m, 4H), 1.61 – 1.50 (m,3H), 1.46 – 1.36 (m, 3H), 1.34 – 1.25 (m, 4H), 1.16 – 1.00 (m, 5H), 0.96 (t, J = 7.3 Hz, 3H), 0.83 (d, J = 7.0 Hz, 3H), 0.61 (d, J = 6.8 Hz, 3H). 13 C NMR (101MHz, Chloroform- d ) δ 217.30, 168.40, 158.69, 139.29, 133.84, 124.98, 116.88,115.14, 74.36, 69.41, 67.36, 63.90, 63.82, 58.18, 51.21, 45.45, 44.63, 43.92,41.70, 38.83, 36.75, 36.01, 34.51, 30.41, 28.67, 26.83, 26.67, 24.84, 24.66,23.11, 22.59, 19.63, 16.68, 14.84, 13.74, 11.56. Compound 14, yield 89%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.30 (d, J = 8.8 Hz,2H), 6.74 (d, J= 8.8 Hz, 2H), 6.33 (dd, J = 17.4, 11.0 Hz, 1H), 5.62 (d, J = 8.4Hz, 1H), 5.24 (dd, J = 10.9, 1.6 Hz, 1H), 5.09 (dd, J = 17.5, 1.7 Hz, 1H), 3.90(t, J = 6.0 Hz, 2H), 3.65 – 3.50 (m, 2H), 3.49 – 3.42 (m, 2H), 3.39 (d, J = 7.2Hz, 2H), 3.37 – 3.27 (m, 7H), 2.32 – 2.08 (m, 3H), 2.05 (s, 1H), 1.90 (dd, J =16.1, 8.5 Hz, 1H), 1.80 (dq, J = 16.2, 8.9, 7.5 Hz, 5H), 1.66 (tdd, J = 17.4,8.5, 6.1 Hz, 4H), 1.55 (qd, J = 8.2, 3.9 Hz, 3H), 1.48 – 1.39 (m, 1H), 1.40 –1.22 (m, 10H), 1.04 (d, J = 22.3 Hz, 5H), 0.95 – 0.73 (m, 6H), 0.60 (d, J = 6.8Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.31, 168.38, 158.69, 139.30,133.82, 124.95, 116.83, 115.13, 74.33, 69.42, 67.36, 64.07, 63.79, 58.17,51.21, 45.44, 44.62, 43.91, 41.69, 38.82, 36.73, 36.01, 34.51, 31.25, 30.40,28.65, 26.81, 26.69, 25.90, 24.82, 23.09, 22.73, 22.57, 22.39, 16.66, 14.83,13.91, 11.56. Compound 15, yield 87%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.33 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 6.36 (dd, J = 17.4, 11.0 Hz, 1H), 5.65 (d, J = 8.4Hz, 1H), 5.27 (dd, J = 11.0, 1.6 Hz, 1H), 5.12 (dd, J = 17.4, 1.7 Hz, 1H), 3.92(t, J = 6.0 Hz, 2H), 3.67 – 3.53 (m, 2H), 3.51 – 3.23 (m, 11H), 2.32 – 2.10 (m,3H), 2.05 (d, J = 2.6 Hz, 1H), 1.92 (dd, J = 16.0, 8.5 Hz, 1H), 1.88 – 1.73 (m,5H), 1.67 (ddd, J = 13.3, 5.2, 2.5 Hz, 3H), 1.64 – 1.50 (m, 3H), 1.52 – 1.41(m, 1H), 1.38 – 1.17 (m, 15H), 1.14 – 0.98 (m, 5H), 0.95 – 0.76 (m, 6H), 0.62(d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d) δ 217.29, 168.40, 158.69,139.27, 133.85, 125.00, 116.90, 115.14, 74.38, 69.40, 67.34, 64.05, 63.76,58.18, 51.22, 45.45, 44.64, 43.92, 41.71, 38.83, 36.75, 36.01, 34.51, 31.62,30.41, 29.16, 29.03, 28.68, 26.83, 26.64, 26.27, 24.84, 23.11, 22.81, 22.59, 22.57, 16.69, 14.85, 14.07, 11.55. Compound 16, yield 78%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.33 (d, J = 8.7 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 6.35 (dd, J = 17.4, 11.0 Hz, 1H), 5.64 (d, J = 8.4Hz, 1H), 5.26 (dd, J = 11.0, 1.6 Hz, 1H), 5.12 (dd, J = 17.5, 1.7 Hz, 1H), 3.92(t, J = 6.0 Hz, 2H), 3.64 – 3.52 (m, 2H), 3.51 – 3.25 (m, 11H), 2.32 – 2.10 (m,3H), 2.05 (s, 1H), 1.92 (dd, J = 16.0, 8.5 Hz, 1H), 1.79 (dddd, J = 18.6, 15.2,9.7, 4.5 Hz, 6H), 1.67 (ddd, J = 13.3, 5.2, 2.5 Hz, 3H), 1.63 – 1.38 (m, 6H), 1.38 – 1.18 (m, 16H), 1.14 – 0.96 (m, 5H), 0.91 – 0.77 (m, 6H), 0.62 (d, J =6.8 Hz, 3H). 13C NMR (101 MHz, Chloroform- d ) δ 217.28, 168.41, 158.69, 139.26,133.86, 125.02, 116.92, 115.14, 74.40, 69.40, 67.34, 64.07, 63.77, 58.19,51.23, 45.46, 44.64, 43.92, 41.71, 38.83, 36.76, 36.01, 34.51, 31.82, 30.42,29.41, 29.38, 29.23, 28.68, 26.83, 26.62, 26.28, 24.84, 23.12, 22.82, 22.65, 22.60, 16.69, 14.85, 14.12, 11.55. Compound 17, yield 80%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.31 (d, J = 8.7 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H), 6.32 (dd, J = 17.4, 11.0 Hz, 1H), 5.62 (d, J = 8.4Hz, 1H), 5.23 (dd, J = 11.0, 1.6 Hz, 1H), 5.08 (dd, J = 17.5, 1.7 Hz, 1H), 3.88(t, J = 6.2 Hz, 2H), 3.48 (tt, J = 13.9, 5.6 Hz, 4H), 3.40 (d, J = 4.2 Hz, 2H),3.37 – 3.23 (m, 7H), 2.28 – 2.19 (m, 2H), 2.18 – 2.10 (m, 1H), 2.04 (d, J = 2.6Hz, 1H), 1.90 (dd, J= 16.0, 8.4 Hz, 1H), 1.78 – 1.61 (m, 8H), 1.60 – 1.48 (m,3H), 1.47 – 1.35 (m, 6H), 1.32 (s, 3H), 1.30 – 1.25 (m, 1H), 1.15 – 1.00 (m,5H), 0.95 (t, J = 7.3 Hz, 3H), 0.82 (d, J = 7.0 Hz, 3H), 0.60 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.27, 168.35, 158.82, 139.35, 133.79,124.78, 116.76, 115.15, 74.32, 69.42, 67.48, 63.85, 58.19, 51.19, 45.45,44.65, 43.91, 41.71, 38.82, 36.74, 36.04, 34.50, 30.42, 28.87, 26.82, 26.72,25.95, 25.71, 24.85, 24.65, 22.79, 19.62, 16.63, 14.83, 13.72, 11.56. Compound 18, yield 86%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.32 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 6.33 (dd, J = 17.4, 11.0 Hz, 1H), 5.63 (d, J = 8.4Hz, 1H), 5.24 (dd, J = 10.9, 1.6 Hz, 1H), 5.09 (dd, J = 17.4, 1.7 Hz, 1H), 3.89(t, J = 6.1 Hz, 2H), 3.56 – 3.42 (m, 4H), 3.41 (d, J = 3.8 Hz, 2H), 3.38 – 3.28(m, 7H), 2.24 (q,J = 5.4, 4.2 Hz, 1H), 2.23 – 2.15 (m, 1H), 2.14 – 2.08 (m,1H), 2.05 (d, J = 2.6 Hz, 1H), 1.90 (dt, J = 19.2, 9.5 Hz, 1H), 1.80 – 1.62 (m,8H), 1.60 – 1.47 (m, 4H), 1.43 (ddd, J = 16.8, 9.5, 2.9 Hz, 4H), 1.37 – 1.25(m, 9H), 1.14 – 0.98 (m, 5H), 0.85 (q, J = 6.9 Hz, 6H), 0.61 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.26, 168.36, 158.82, 139.33, 133.80,124.81, 116.79, 115.15, 74.35, 69.42, 67.47, 64.01, 63.83, 58.19, 51.23,45.45, 44.66, 43.92, 41.71, 38.82, 36.75, 36.04, 34.50, 31.25, 30.43, 28.87,26.83, 26.69, 25.95, 25.90, 25.72, 24.85, 22.80, 22.73, 22.38, 16.64, 14.84, 13.88, 11.55. Compound 19, yield 78%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.32 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 6.33 (dd, J = 17.4, 11.0 Hz, 1H), 5.63 (d, J = 8.4Hz, 1H), 5.24 (dd, J = 11.0, 1.6 Hz, 1H), 5.09 (dd, J= 17.5, 1.7 Hz, 1H), 3.89(t, J = 6.2 Hz, 2H), 3.59 – 3.47 (m, 2H), 3.47 – 3.39 (m, 4H), 3.38 – 3.26 (m,7H), 2.29 – 2.08 (m, 3H), 2.04 (d, J = 2.6 Hz, 1H), 1.91 (dd, J = 16.0, 8.5 Hz,1H), 1.79 – 1.61 (m, 8H), 1.60 – 1.47 (m, 3H), 1.41 (dtd, J = 20.1, 9.9, 9.3,4.6 Hz, 4H), 1.35 – 1.29 (m, 7H), 1.29 – 1.17 (m, 7H), 1.12 – 0.92 (m, 5H), 0.84 (td, J = 6.8, 2.0 Hz, 6H), 0.61 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 217.25, 168.36, 158.82, 139.33, 133.80, 124.80, 116.79,115.15, 74.34, 69.42, 67.47, 64.00, 63.81, 58.19, 51.23, 45.45, 44.65, 43.91,41.71, 38.82, 36.75, 36.04, 34.50, 31.60, 30.43, 29.66, 29.13, 29.00, 28.88,26.82, 26.69, 26.25, 25.95, 25.72, 24.85, 22.79, 22.54, 16.64, 14.84, 14.04, 11.55. Compound 20, yield 75%. 1 H NMR (400 MHz, Chloroform- d ) δ 7.33 (d, J = 8.7 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 6.34 (dd, J= 17.5, 11.0 Hz, 1H), 5.65 (d, J = 8.4Hz, 1H), 5.26 (dd, J = 11.0, 1.6 Hz, 1H), 5.10 (dd, J = 17.5, 1.7 Hz, 1H), 3.90(t, J = 6.1 Hz, 2H), 3.62 – 3.51 (m, 2H), 3.50 – 3.40 (m, 4H), 3.40 – 3.29 (m,7H), 2.30 – 2.10 (m, 3H), 2.06 (d, J = 2.6 Hz, 1H), 1.92 (dd, J = 16.0, 8.5 Hz,1H), 1.80 – 1.63 (m, 8H), 1.62 – 1.50 (m, 3H), 1.44 (ddd, J = 17.1, 9.4, 3.0Hz, 4H), 1.38 – 1.31 (m, 7H), 1.29 – 1.21 (m, 11H), 1.13 – 0.96 (m, 5H), 0.92– 0.75 (m, 6H), 0.63 (d, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ217.22, 168.37, 158.83, 139.32, 133.81, 124.84, 116.82, 115.15, 74.38, 69.41,67.46, 64.01, 63.82, 58.20, 51.23, 45.46, 44.67, 43.92, 41.72, 38.83, 36.76,36.04, 34.50, 31.80, 30.44, 29.67, 29.39, 29.36, 29.21, 28.89, 26.84, 26.66,26.27, 25.96, 25.74, 24.86, 22.82, 22.63, 16.65, 14.85, 14.09, 11.55. Application Example 1: The in vitro antibacterial activity of compounds 1-20, tiamulin, and vancomycin prepared in Example 1 was determined.

[0035] Test bacteria: Staphylococcus aureus standard strain (Staphylococcus aureus ATCC 29213); methicillin-resistant Staphylococcus aureus. Staphylococcus aureus MRSA). Samples and reagents: Tiamulin, vancomycin, and compounds 1-20 prepared in the examples. Test methods are as follows: According to the Clinical and Laboratory Standards Institute (CLSI) standards, the in vitro antibacterial activity of compounds 1-20 of this invention and the clinical antibacterial drugs tiamulin and vancomycin was tested using 96-well plates and serial dilution methods. The minimum inhibitory concentration (MIC) was defined as the drug concentration observed in the smallest completely clear well. Table 1 shows the in vitro antibacterial activity (μg / mL) of compounds 1-20, tiamulin, and vancomycin, which contain long-chain quaternary ammonium salt side chains prepared in this invention.

[0036] Table 1 Note: Sa a Staphylococcus aureus ATCC 29213, Ec b Escherichia coli ATCC 25922, Van: vancomycin, Tia: tiamulin, Com: compound, HC 50 : Half-maximal hemolytic concentration.

[0037] As shown in Table 1, the truncated pleurotin derivatives containing long-chain quaternary ammonium salt side chains prepared in this invention exhibit good antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). Compared with the clinical drug tiamulin, the antibacterial activity against MRSA was improved in all compounds. Compounds 11, 12, 13, and 14 showed good antibacterial activity, with MIC values ​​against MRSA ranging from 1 to 4 μg / mL, which is approximately 32-128 times lower than that of tiamulin. Regarding hemolytic toxicity, the gradual increase in tail chain length led to increased hemolytic toxicity, while compound 13 maintained good hemolytic toxicity. Therefore, compound 13 has the advantages of high anti-MRSA activity and low biotoxicity.

[0038] Application Example 2: In vitro time-killing kinetics experiment: 1. Test bacteria: MRSA-GH23 (clinical isolate) 2. Samples and reagents: The samples were: vancomycin, tiamulin, and compound 13 prepared in Example 1.

[0039] Test Method: A single colony of MRSA was picked from a clean bench and added to 3 ml of BHI broth. The mixture was incubated at 37°C and 200 rpm for 12 h, then diluted 1:1000 into 3 ml of sterilized BHI broth. The test drugs were added. Compound 13 was prepared at concentrations of 4×MIC and 8×MIC, and vancomycin was prepared at concentrations of 4×MIC and 8×MIC. A blank control group without any drugs was also included. Then, the expected concentrations of the compound and the positive control vancomycin were added, while the negative control was added to PBS. 30 μL of bacterial culture was added to each tube containing a different concentration, mixed, and incubated on a shaker at 37°C. At 0, 0.5, 1, 2, 4, 6, and 8 h, 100 μL of the sample was added to 900 μL of PBS, mixed, and then 100 μL of this 1 mL was added to 900 μL of PBS; this was repeated in a 10-fold serial dilution series. Take 100 μL of bacterial suspension at different dilutions and spread it evenly on BHI medium, with three replicates for each dilution. Incubate the medium at 37°C for 24 h. Perform the same procedure for other groups. Incubate overnight at 37°C and count the colonies (unit: log). 10 CFU / mL and plotted a curve based on the statistical results, as shown below. Figure 1 As shown. Figure 1 This indicates that compound 13 has a rapid antibacterial effect against MRSA. Compared with vancomycin, compound 13 can control bacterial growth in a short time and kill them rapidly, while vancomycin only effectively inhibits bacterial growth and reproduction without killing them. Therefore, compound 13 shows promise for development into a rapid antibacterial agent for clinical use.

[0040] Application Example 3: In vivo and in vitro safety evaluation experiments of compound 13 1. Cytotoxicity of compound 13: Reagents: Compound 13; Test cells: Vero cells; Test method: When the cells have been passaged to 3-6 generations, the Vero cells are digested from the flask wall with trypsin to prepare a cell suspension, and the cell number is adjusted to approximately 1×10⁻⁶. 5 Cells / mL. Seed 100 μL / well into a 96-well plate, then add 100 μL of the test solution. Set up a blank group (culture medium only), a control group (cell suspension only), and an experimental group; incubate at 37℃, 5% CO2 for 24 h. After cell attachment, add different concentrations of the test solution and continue incubation for another 24 h. After incubation, add 10 μL of CCK-8 reagent to each well in the dark, gently tap the edge of the plate to promote mixing while avoiding air bubbles, and incubate in the dark for 1–4 h; measure OD using a microplate reader. 450 Record data from each well and calculate cell viability. The calculation method is: Cell viability (%) = (OD of drug-treated group) / ... 450-Culture group OD 450 ) / (Cellular OD 450 -Culture group OD 450 () × 100%. The IC50 can be obtained by simulating the relationship between the concentration of the test solution and cell viability using GraphPad Prism software. 50 value. Figure 2 The results showed that at a compound 13 concentration of 64 μg / mL, the survival rate of Vero cells induced by compound 13 was approximately 59%, while at a concentration of 32 μg / mL, Vero cell viability remained at a high level of 80%. The IC50 was calculated using linear regression. 50 The value was 131.8 μg / mL. Therefore, compound 13 has relatively low toxicity to normal mammalian kidney cells.

[0041] 2. In vivo toxicity of compound 13: Reagent: Compound 13. Test animals: SPF-grade BALB / c mice; Test method: SPF-grade female BALB / c mice, 6–8 weeks old and weighing approximately 18–20 g, were selected. Mice were randomly divided into 5 groups of 6 mice each, with 4 compound administration groups (10 mg / kg, 20 mg / kg, 30 mg / kg, and 50 mg / kg), and a blank control group (0.9% NaCl). Compounds of appropriate concentrations were prepared using physiological saline as a solvent according to the mice's body weight. Each group of mice received a single intraperitoneal injection of 100 μL, while the control group received an equal volume of physiological saline concurrently. Mice were observed for 72 h after administration, during which time they had free access to food and water. The mice's condition and survival were recorded throughout the observation period, and the 72-h survival rate was calculated. No mouse deaths were observed after 72 h. Twelve mice were then randomly divided into two groups: a blank control group (0.9% NaCl) and a compound 13 group (50 mg / kg). Blood was collected from the eyeball 24 hours after a single administration for routine blood tests and blood biochemistry tests to evaluate the blood toxicity of the test substance. Figure 3 The results showed that the white blood cell count (WBC), hematocrit (HCT), red blood cell count (RBC), hemoglobin (HGB), mean corpuscular volume (MCV), and platelet count (PLT) were not significantly different from those of the control saline group. Furthermore, the levels of albumin (ALB), urea (UREA), and creatinine (CREA) in blood biochemistry did not show significant differences compared to the control group. These data indicate that compound 13 did not cause hemolysis, tissue damage, or acute inflammatory response in mice, and that the normal function of the liver and kidneys was not affected, suggesting that it is relatively safe in vivo.

[0042] Application Example 4: In vivo anti-MRSA infection activity experiment of compound 13 Test bacteria: MRSA-GH23; Samples and reagents: Vancomycin and Compound 13 prepared in Example 1; Test animals: SPF-grade BALB / c mice. Test method: Thirty healthy female BALB / c mice (weighing 18–20 g, 6–8 weeks old) were selected. The mice were divided into 5 groups: control group (saline treatment group), Compound 13 treatment group (20 mg / kg, 10 mg / kg, and 5 mg / kg), and vancomycin treatment group (5 mg / kg). The revived MRSA strain GH23 was inoculated into BHI broth and cultured to the logarithmic growth phase. It was then inoculated into 50 mL of BHI medium at a 1:100 ratio and cultured at 180 rpm and 37°C for 4 h. After anesthesia, the mice were subcutaneously injected into the back with MRSA bacterial solution (50 μL, 5 × 10⁻⁶ g / kg). 8 After 30 minutes, 50 μL of different concentrations of compound 13, vancomycin, and physiological saline were subcutaneously injected into the injection site, and the injection sites were marked. The mice were closely monitored after injection, and the injection sites were monitored for 48 hours, noting any observable adverse skin reactions. Then, all 30 mice were euthanized, and 3 mice were selected from each group. 100 mg of the skin was extracted and placed in a centrifuge tube containing 1 ml PBS. The tissue was then homogenized and centrifuged. 100 μL of the homogenate supernatant was serially diluted, and 100 μL was evenly spread onto BHI plates. The bacterial load on the mouse skin was recorded after 24 hours. The results are as follows: Figure 4 As shown. Figure 4 The results showed that, compared with the control group, treatment with vancomycin (5 mg / kg) and compound 13 (5, 10, and 20 mg / kg) significantly reduced MRSA bacterial load. When the concentration of compound 13 was 10 mg / kg, the bacterial load decreased by approximately 3.2 log. 10 CFU / g. Furthermore, bacterial load decreased by approximately 1.16 Log in treatments with 5 mg / kg compound 13 and vancomycin. 10 CFU / g and 1.51 Log 10 CFU / g. The therapeutic effect of compound 13 at twice the dose was comparable to that of vancomycin. Based on the in vivo antibacterial activity of compound 13, it exhibits good stability in vivo while maintaining the same good bactericidal activity as in vitro, making it a promising candidate for clinical application as an antibacterial drug.

[0043] Application Example 5: Antibacterial Mechanism Test of Compound 13 1. Scanning electron microscopy: Reagents: Compound 13, 2.5% glutaraldehyde; Test bacteria: MRSA-GH23 (clinical isolate). Test method: Pick a single colony of GH23 and place it in 3 ml of BHI broth. Incubate at 37°C and 200 rpm for 5 h in a constant temperature shaker. Dilute to 1×10⁻⁶. 5 CFU / mL. Compound 13 (16×MIC) was added to the bacterial suspension, with an untreated bacterial suspension serving as a positive control. After incubation at 37°C and 200 rpm for 4 h, the suspension was centrifuged (5000 rpm, 4°C, 5 min), and the supernatant was discarded. The bacteria were washed three times with 1×PBS, fixed with 1 mL of 2.5% glutaraldehyde fixative, stored overnight at 4°C, dehydrated with gradient concentrations of ethanol, and then subjected to critical point drying and gold sputtering. Morphological changes were observed using a high-resolution field emission scanning microscope. Figure 5 In samples A and C, untreated MRSA cells were observed to be arranged in a typical spherical or grape-like pattern, with a uniform distribution. The cell surface was smooth, round, and plump, with an intact cell wall structure and clear boundaries. Figure 5 As shown in Figures B and D, the morphology of MRSA underwent significant changes after drug treatment. The cells no longer maintained a regular spherical shape, exhibiting obvious shrinkage, collapse, and irregular deformation. The cell surface became rough, and intracellular material leakage and abnormal fusion between cells were observed. Broken cell debris was visible in some areas, indicating that compound 13 can cause severe damage to the MRSA cell membrane.

[0044] 2. Membrane depolarization test: Reagents: Compound 13, DiSC3(5); Test bacteria: MRSA-GH23 (clinical isolate); Test method: The effect of compound 13 on the depolarization of the GH23 cell membrane was evaluated using 3,3'-dipropylthiodicyanine iodide [DiSC3(5)]. GH23 cells were cultured to the logarithmic growth phase (1×10⁻⁶). 8 CFU / mL), the bacterial suspension was centrifuged (4℃, 3500 rpm, 5 min), the supernatant was collected, washed 3 times with PBS, and then the bacterial pellet was resuspended in PBS. 150 μL of bacterial suspension and DiSC3(5) (10 μM, 40 μL) were mixed in a black 96-well plate and incubated at 37℃ in the dark for 30 min. Then, the fluorescence intensity was recorded every 2 min at an excitation / emission wavelength of 622 / 670 nm using a microplate reader. After 10 min of continuous testing, 10 μL of compound 13 with final concentrations of 2, 4, 8, 16, and 32 μg / mL and melitoxin 32 μg / mL were added to the wells as positive controls, and the fluorescence intensity was monitored every 2 min for another 20 min. PBS was used as a blank control. Figure 6As shown, different concentrations of compound 13 (8, 16, and 32 μg / mL) and melittin (32 μg / mL) were added at 10 min. The results showed that the fluorescence intensity in the blank control group remained essentially unchanged; however, after the addition of the drugs, the fluorescence intensity increased rapidly and significantly, exhibiting a clear concentration dependence. At a concentration of 8 μg / mL, compound 13 induced significant membrane depolarization; when the concentration was increased to 16 μg / mL, the degree of membrane depolarization it caused was comparable to that of melittin at 32 μg / mL; and at 32 μg / mL, its disruptive effect on membrane potential was significantly superior to that of melittin at the same concentration.

[0045] 3. DNA and protein leakage test: Reagents: Compound 13; Test bacteria: MRSA-GH23 (clinical isolate). Test method: Take a single GH23 colony and incubate it in 3 mL of BHI liquid medium (200 rpm, 37℃) for 6 h. Centrifuge the bacterial culture and discard the supernatant (3500 rpm, 4℃, 5 min). Wash three times with PBS buffer, then resuspend in PBS buffer to adjust the bacterial concentration to 1×10⁻⁶. 6 CFU / mL. Then, compound 13 was added to final concentrations of 2×, 4×, 8×, and 16× MIC, and the mixture was incubated at 37℃ and 200 rpm for 4 h. After incubation, the bacterial cultures of each group were centrifuged at 3500 rpm for 5 min at 4℃, and the supernatant was retained. Finally, the DNA concentration in the supernatant was measured using a microspectrophotometer, and the protein concentration was quantitatively determined using a BCA protein concentration kit. Figure 7 In the diagram, A represents the experimental results of DNA leakage, and B represents the experimental results of protein leakage. Figure 7 As shown, compound 13 can induce DNA and protein leakage in MRSA in a dose-dependent manner, indicating that compound 13 can cause cell membrane disruption in MRSA, leading to leakage of intracellular proteins and DNA.

[0046] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain, characterized in that, Its general chemical structural formula is: ； Where n = 0, 1, 2, 3 or 4; m = 1, 3, 5 or 7.

2. A method for preparing the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain as described in claim 1, characterized in that, Includes the following steps: S1. Intermediate I was obtained by acylation reaction using truncated pleurotin and p-toluenesulfonyl chloride as raw materials; S2. Using the intermediate I and p-hydroxythiophenol as raw materials, intermediate II is obtained through a nucleophilic substitution reaction under alkaline conditions; S3. Intermediate II reacts with dibromoalkane via a nucleophilic substitution reaction to yield intermediate III; S4. The intermediate III undergoes a quaternization reaction with a tertiary amine to obtain the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain.

3. The preparation method according to claim 2, characterized in that, The chemical structural formula of intermediate I is: ； The chemical structural formula of intermediate II is: ; The chemical structural formula of intermediate III is as follows: , where n = 0, 1, 2, 3 or 4.

4. The preparation method according to claim 2, characterized in that, In step S1, the acylation reaction is carried out at room temperature, and the molar ratio of truncated pleurotin to p-toluenesulfonyl chloride is 1:1.

2. In step S2, the nucleophilic substitution reaction is carried out at a temperature of 70°C, and the molar ratio of intermediate I to p-hydroxythiophenol is 1:1.

5. In step S3, the nucleophilic substitution reaction is carried out at a temperature of 75°C, and the molar ratio of intermediate II to dibromoalkane is 1:1.

5. In step S4, the temperature of the quaternization reaction is 90°C, and the molar ratio of intermediate III to tertiary amine is 1:

1.

5. A pharmaceutically acceptable salt, a solvent compound of the acceptable salt, an enantiomer, a diastereomer, and a tautomer of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain as claimed in claim 1, and a mixture of the pharmaceutically acceptable salt, the solvent compound of the acceptable salt, the enantiomer, the diastereomer, and the tautomer in any proportion of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain.

6. The use of the truncated pleurotin derivative containing a long-chain quaternary ammonium salt side chain as claimed in claim 1, and its pharmaceutically acceptable salt, solvent compound of the acceptable salt, enantiomer, diastereomer and tautomer in the preparation of a pharmaceutical formulation for treating bacterial infectious diseases.

7. The application according to claim 6, characterized in that, The pharmaceutical preparation for treating bacterial infectious diseases is an oral administration preparation or a non-oral administration preparation; the oral administration preparation includes tablets, capsules, granules, syrups, premixes, or microcapsules; the non-oral administration preparation includes liniments and injections.

8. A pharmaceutical composition, characterized in that, Its active ingredient includes the truncated pleurotin derivative with a long-chain quaternary ammonium salt side chain as described in claim 1; Or it may include pharmaceutically acceptable salts, solvent compounds of acceptable salts, enantiomers, diastereomers and tautomers of the truncated pleurotin derivatives containing long-chain quaternary ammonium salt side chains as described in claim 5.

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