Aryl dihydronaphthalene lignan analogue with antibacterial activity as well as preparation method and application of aryl dihydronaphthalene lignan analogue

Abstract

The invention relates to the technical field of pharmacy, in particular to an aryl dihydronaphthalene type lignan analogue with antibacterial activity as well as a preparation method and application thereof, and the aryl dihydronaphthalene type lignan analogue is a compound with a structure as shown in a formula (I) or a pharmaceutically acceptable prodrug thereof. The specific preparation method comprises the following steps: (1) carrying out ring opening on sesamin ether bonds to prepare acetate 2; (2) performing deacetylation protection on the compound 2 to prepare alcohol 3; and (3) carrying out Des-Martin oxidation on the alcohol 3 to prepare aldehyde 4 and aldehyde 5. The aryl dihydronaphthalene lignan analogue synthesized by the invention has certain activity on Candida albicans (C.albicans), Cryptococcus neoformans (C.neoformans) and T.mentagrophytes (T.mentagrophytes), the compound 5 has good activity on the three types of bacteria, the IC50 values of the three types of bacteria are respectively 28.96 mu M, 17.13 mu M and 41.35 mu M, and the aryl dihydronaphthalene lignan analogue has certain application prospects in the development of corresponding medicines.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and in particular to an aryldihydronaphthalene-type lignan analogue with antibacterial activity, a preparation method and an application thereof. Background Art

[0002] Fungal infections pose an increasingly serious threat to human health worldwide, especially invasive fungal infections (IFDs), whose incidence is increasing year by year, with an annual growth rate of approximately 0.9% and an annual incidence of 2.72 cases per 10,000 patients. IFDs primarily affect immunocompromised patients (malignant tumor patients, transplant recipients, and patients in intensive care units), with a mortality rate as high as 27.6%, and even up to 39%-100% in certain high-risk populations. Currently, the main drugs used in the clinical treatment of invasive fungal infections include triazoles, polyenes, and echinocandins. These drugs are subject to increasing drug resistance, significant toxic side effects, and high treatment costs, posing significant challenges to clinical treatment. Therefore, the development of novel, highly effective, and low-toxic antifungal drugs is urgent.

[0003] Aryldihydronaphthalene lignans (ANLs) are a class of naturally occurring compounds widely distributed in plants with diverse biological activities, including antitumor, anti-inflammatory, antioxidant, and antifungal properties. In recent years, the antifungal activity of aryldihydronaphthalene lignans has attracted considerable attention. For example, aryldihydronaphthalene lignans from Vitex negundo not only exhibit broad-spectrum antitumor activity but also inhibit a variety of pathogenic fungi, including Candida albicans and Trichophyton mentagrophytes. However, natural aryldihydronaphthalene lignan analogs are underutilized, exhibit minimal activity, are structurally complex, and lack systematic research. Given the molecular diversity of lignan compounds, novel aryldihydronaphthalene lignan analogs have been designed and synthesized through structural modification and optimization of aryldihydronaphthalene lignans. These analogs retain the active skeletal structure of natural lignans while incorporating specific functional groups to enhance their antimicrobial activity. The present invention uses sesamin as a raw material and synthesizes aryl dihydronaphthalene lignan analogues through reactions such as ring opening, deprotection and oxidation. The aryl dihydronaphthalene lignan analogues have good antifungal activity. Through the implementation of the present invention, it is expected to provide a solution for the treatment of fungi. Summary of the Invention

[0004] The purpose of the present invention is to address the above-mentioned problems and provide an aryl dihydronaphthalene type lignan analogue with antibacterial activity, a preparation method and an application thereof. The present invention designs and synthesizes an aryl dihydronaphthalene type lignan analogue, which has good antibacterial activity.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention provides an aryl dihydronaphthalene lignan analogue with antibacterial activity. The aryl dihydronaphthalene lignan analogue is a compound having a structure of formula (I), or a pharmaceutically acceptable prodrug thereof.

[0007]

[0008] Wherein, R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen, hydroxyl, aldehyde, amino, acetyl, carboxyl, cyano, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, substituted or unsubstituted 5-10 membered aryl or 5-10 membered heteroaryl.

[0009] Furthermore, the aryldihydronaphthalene-type lignan analog is compound 2-5 or a pharmaceutically acceptable prodrug thereof.

[0010] The present invention also provides a method for preparing the aryldihydronaphthalene-type lignan analogs, and the synthetic route is as follows:

[0011]

[0012] The specific preparation method comprises the following steps:

[0013] (1) Sesamin ether bond is opened to prepare compound 2:

[0014] Sesamin was dissolved in a mixture of dichloromethane (DCM) and acetic anhydride (Ac2O), cooled to 0°C, and an appropriate amount of AlCl3 was added. The reaction was continued for 2-3 hours, and then a saturated sodium bicarbonate solution was added to quench the reaction. The mixture was extracted with dichloromethane and purified by silica gel column chromatography to obtain compound 2.

[0015] (2) Deacetylation to prepare compound 3:

[0016] Compound 2 was dissolved in methanol, potassium carbonate and water were added, and the mixture was reacted at room temperature for 2-3 hours. Methanol and water were removed under reduced pressure, and 10-100 mL of dichloromethane was added to dissolve the mixture. Potassium carbonate was removed by filtration, and the filtrate was concentrated to obtain a crude product. The crude product was purified by silica gel column to obtain compound 3;

[0017] (3) Dess-Martin oxidation to prepare compound 4

[0018] Compound 3 was dissolved in dichloromethane, sodium bicarbonate was added at 0°C, and the mixture was stirred for 5-10 minutes. Dess-Martin oxidant was then slowly added in batches. The reaction was continued at 0°C for 2-3 hours and monitored by TLC. After the reaction was completed, water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic phase was purified by silica gel column chromatography to obtain compound 4.

[0019] (4) Preparation of Compound 5

[0020] Compound 3 was dissolved in acetonitrile, sodium bicarbonate was added at 0°C, and the mixture was stirred for 5-10 minutes. Dess-Martin oxidant was then slowly added in batches, and the mixture was heated to room temperature for 2-3 hours. After the reaction, water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic phase was purified by silica gel column chromatography to obtain compound 5.

[0021] Preferably, in the above preparation method, the molar ratio of sesamin and AlCl3 in step (1) is 1:1.2, and the volume ratio of dichloromethane to acetic anhydride is 2:1.

[0022] Preferably, in the above preparation method, the molar ratio of compound 2 to potassium carbonate in step (2) is 1:2, and the volume ratio of methanol to water is 10:1.

[0023] Preferably, in the above preparation method, the molar ratio of compound 3, sodium bicarbonate and Dess-Martin oxidant in step (3) is 1:3:1.5; in this step, the solvent used is dichloromethane, and when the reaction temperature is maintained at 0°C, the main product is compound 4;

[0024] Preferably, in the above preparation method, the molar ratio of compound 3, sodium bicarbonate and Dess-Martin oxidant in step (4) is 1:4:2.4; in this step, the solvent used is acetonitrile, and when the reaction temperature is raised from 0°C to room temperature, the main product is compound 5.

[0025] In addition, the present invention also provides the use of the aryl dihydronaphthalene type lignan analogue in the preparation of antibacterial drugs.

[0026] Preferably, the application includes the use of the aryldihydronaphthalene lignan analogs or pharmaceutically acceptable salts, isomers, solvates thereof in the preparation of antifungal drugs.

[0027] Preferably, the fungi are Candida albicans, Cryptococcus neoformans and Trichophyton mentagrophytes.

[0028] Furthermore, a pharmaceutical composition is provided, which comprises the aryldihydronaphthalene lignan analogue or a pharmaceutically acceptable salt, isomer, solvate thereof and a pharmaceutically acceptable carrier or excipient.

[0029] In summary, due to the adoption of the above technical solution, the present invention has the following beneficial effects:

[0030] 1. This invention is the first to design and synthesize novel structural aryldihydronaphthalene-type lignan analogs using cheap and readily available sesamin as a raw material. The synthesized compounds 2-5 were screened for antibacterial activity, demonstrating that they possess good antibacterial activity and are expected to achieve high-value utilization of sesamin.

[0031] 2. The aryl dihydronaphthalene lignan analogs designed and synthesized by the present invention have good antibacterial activity. Experimental data show that the IC of compound 2 against Cryptococcus neoformans (C.neoformans) and Trichophyton mentagrophytes (T.mentagrophytes) is 2. 50 The IC values of compound 3 against Candida albicans and Cryptococcus neoformans were 32.54 μM and 40.25 μM, respectively. 50 The IC values of compound 4 against Candida albicans were 33.16 μM and 41.25 μM respectively; 50 Compound 5 has good antibacterial activity against Cryptococcus neoformans, Candida albicans and Trichophyton mentagrophytes, and its IC 50 The above data show that the synthetic aryldihydronaphthalene lignan analogs of the present invention have good antibacterial activity and have certain application prospects in the development of corresponding drugs. DETAILED DESCRIPTION

[0032] In order to help those skilled in the art better understand the present invention, the following clearly and completely describes the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work should fall within the scope of protection of the present invention.

[0033] The present invention provides an aryl dihydronaphthalene lignan analogue with antibacterial activity. The aryl dihydronaphthalene lignan analogue is a compound having a structure of formula (I), or a pharmaceutically acceptable prodrug thereof.

[0034]

[0035] Wherein, R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen, hydroxyl, aldehyde, amino, acetyl, carboxyl, cyano, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, substituted or unsubstituted 5-10 membered aryl or 5-10 membered heteroaryl.

[0036] Furthermore, the aryldihydronaphthalene-type lignan analog is compound 2-5 or a pharmaceutically acceptable prodrug thereof.

[0037]

[0038] The present invention also provides a method for preparing the aryldihydronaphthalene-type lignan analogs, and the synthetic route is as follows:

[0039]

[0040] In order to express the present invention more clearly, the present invention is further described below through specific examples.

[0041] 1. Preparation Example

[0042] Example 1: Preparation of Compound 2

[0043] Sesamin (1.0 g, 2.8 mmol) was dissolved in 40.00 mL of a mixed reagent of dichloromethane and acetic anhydride (the volume ratio of dichloromethane to acetic anhydride was 2:1). After cooling to 0°C, AlCl3 (0.5 g, 3.4 mmol) was added and the reaction was continued for 2-3 h. After the reaction was completed, a saturated sodium bicarbonate solution was added to quench the reaction. The mixture was extracted with dichloromethane, and the organic layer was washed once with water and saturated brine (200.00 mL each of water and saturated brine), then dried over anhydrous Na2SO4, concentrated, and purified by silica gel column chromatography with an eluent of PE:EtOAc = 6:1 to obtain compound 2 as a colorless, transparent oil with a mass of 0.4200 g and a yield of 32.30%.

[0044] The structure of the obtained compound 2 was characterized by nuclear magnetic resonance, and the results are as follows.

[0045] 1H NMR(400MHz,CDCl3,J in Hz)δ(ppm):6.69-6.61(m,2H),6.58(s,1H),6.51-6.44(m,3H),5.91(dd,J =5.33,1.18Hz,2H),5.86(dd,J=5.61,1.23Hz,2H),4.61(d,J=13.03Hz,1H) ,4.52(d,J=12.88Hz,1H),4.18(dd,J=10.94,5.05Hz,1H),4.00(s,1H),3. 84(dd,J=10.88,9.02Hz,1H),2.77-2.69(m,1H),2.06(s,3H),1.93(s,3H). 13 C NMR (100MHz, CDCl3) δ (ppm): 170.97, 170.65, 147.61, 147.54, 146.84, 146.09, 137.33, 129.56, 128.98, 127.98 ,126.43,120.58,110.22,108.13,108.09,107.41,101.16,100.92,66.52,64.36,45.15,43.23,21.02,20.84.

[0046] Example 2: Preparation of Compound 3

[0047] Compound 2 (1.0120 g, 2.28 mmol) was taken and 60.00 mL of methanol was added to completely dissolve it. Potassium carbonate (630.0 mg, 4.56 mmol) and 6.00 mL of water were added and reacted at room temperature for 2-3 h. Methanol and water were removed under reduced pressure. After adding dichloromethane, the potassium carbonate solid was filtered out. Finally, silica gel powder was added and concentrated to obtain a crude product. The crude product was then purified by silica gel column with an eluent of PE:EtOAc = 1:1 to obtain compound 3 with a mass of 725.0 mg and a yield of 89.70%.

[0048] The structure of the obtained compound 3 was characterized by nuclear magnetic resonance, and the results are as follows.

[0049] 1 H NMR(400MHz,CDCl3,J in Hz)δ(ppm):6.68-6.62(m,2H),6.55-6.47(m,3H),6.42(s,1H),5.93-5.89(m,2H),5.89- 5.85(m,2H),4.15-4.05(m,2H),4.05-3.97(m,1H),3.66-3.56(m,2H),2.67-2.61(m,1H). 13C NMR (100MHz, CDCl3) δ (ppm): 147.65, 147.27, 146.74, 146.10, 137.87, 136.12, 129.69, 127.02, 125.58,120.77,110.03,108.25,108.21,107.28,101.13,100.98,66.34,64.73,47.31,45.66.

[0050] Example 3: Preparation of Compound 4

[0051] Compound 3 (1.0 g, 2.82 mmol) was dissolved in 20.00 mL of dichloromethane, and solid sodium bicarbonate (712.0 mg, 8.46 mmol) was added at 0°C and stirred for 5-10 min. Dess-Martin oxidant (1.7900 g, 4.23 mmol) was then slowly added in portions. The reaction was continued at 0°C for 2-3 h and monitored by TLC. After completion of the reaction, water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic phase was purified by silica gel column chromatography with an eluent of DCM:EtOAc = 20:1 to obtain compound 4 with a mass of 715.0 mg and a yield of 72.2%.

[0052] The structure of the obtained compound 4 was characterized by nuclear magnetic resonance, and the results are as follows.

[0053] 1 H NMR(400MHz,CDCl3,J in Hz)δ(ppm):9.55(s,1H),7.27(s,1H),6.86(s,1H),6.68(s,1H),6.64(d,J=7.96Hz,1H),6.48-6.39(m,2H),6.04-5.96(m,2H ),5.90-5.83(m,2H),4.31-4.25(m,1H),3.64(dd,J=10.61,5.65Hz,1H),3.40(dd,J=10.57,8.40Hz,1H),3.25-3.16(m,1H). 13 C NMR (100MHz, CDCl3) δ (ppm): 193.04, 150.61, 147.81, 147.35, 146.76, 146.30, 137.72, 135.36, 134.39,125.15,120.51,110.93,108.97,108.35,108.00,101.86,101.06,63.64,44.51,42.82.

[0054] Example 4: Preparation of Compound 5

[0055] Compound 3 (1.0 g, 2.82 mmol) was dissolved in 20.00 mL of acetonitrile, and solid sodium bicarbonate (1.6 g, 11.3 mmol) was added at 0°C and stirred for 5-10 min. Dess-Martin periodinane (1.3 g, 6.8 mmol) was then slowly added in batches, and the temperature was gradually raised from 0°C to room temperature for 2-3 h. After the reaction was completed, water was added to quench the reaction, and then extracted with dichloromethane. The organic phase was purified by silica gel column chromatography with an eluent of PE:EtOAc = 6:1 to obtain compound 5 with a mass of 535.0 mg and a yield of 53.4%.

[0056] The structure of the obtained compound 5 was characterized by nuclear magnetic resonance, and the results are as follows:

[0057] 1 H NMR(400MHz,CDCl3,J in Hz)δ(ppm):9.69(s,1H),9.49(s,1H),7.45(s,1H),6.85(s,1H),6.71(s,1H),6.65(d,J=8.01Hz,1H) ,6.50-6.38(m,2H),6.00(s,2H),5.91-5.84(m,2H),4.69(d,J=1.75Hz,1H),3.95(d,J=1.79Hz,1H). 13 C NMR (100MHz, CDCl3) δ (ppm): 197.08, 191.57, 151.08, 148.00, 147.61, 147.58, 146.68, 136.36, 1 34.59,130.20,124.62,120.54,110.41,109.23,108.51,107.89,102.00,101.18,52.31,41.84.

[0058] 2. Antibacterial activity test

[0059] 1. Experimental Materials

[0060] (1) Experimental strains: Candida albicans (C.albicans, ATCC10231), Cryptococcus neoformans (C.neoformans, ATCC66031) and Trichophyton mentagrophytes (T.mentagrophytes, ATCC MYA-4439). YM liquid medium (YM); Sabouraud dextrose agar (SDA); potato dextrose agar (PDA); positive control drug fluconazole (FLC) (purchased from Dalian Meilun Biotechnology Co., Ltd., purity 98.5%), dissolved in dimethyl sulfoxide (DMSO), sonicated for 15 minutes, centrifuged to obtain the supernatant, stored at a concentration of 50 mg / mL, and stored in a refrigerator (4°C) in a sealed container. All samples were dissolved in DMSO at a concentration of 50 mg / mL and stored in a refrigerator at 4°C in a sealed container.

[0061] (2) The four target compounds 2-5 synthesized in Examples 1-4.

[0062] 2. Experimental Methods

[0063] The present invention adopts the broth microdilution method to determine the antifungal activity of compounds 2-5 synthesized in Examples 1-4.

[0064] 1. Strain activation

[0065] (1) Activation of Candida albicans: Candida albicans was activated on YM agar solid medium (agar 20.00 g / L; glucose 10.00 g / L; malt extract 3.00 g / L; animal tissue pepsin digest 5.00 g / L; yeast extract 3.00 g / L) and cultured in a 30°C incubator for 24 h.

[0066] (2) Activation of Cryptococcus neoformans: Cryptococcus neoformans was activated on SDA agar solid medium (agar 15.00 g / L; glucose 40.00 g / L; casein trypsin digest, animal tissue gastric digest 10.00 g / L) and cultured in a 30°C incubator for 24 h.

[0067] (3) Activation of Trichophyton mentagrophytes: Trichophyton mentagrophytes were inoculated on potato dextrose agar (PDA) medium and placed in an incubator at 30°C for activation for 7-14 days.

[0068] 2. Preparation of bacterial solution

[0069] (1) Preparation of Candida albicans suspension

[0070] According to the broth microdilution method issued by the US CLSI, several monoclonal Candida albicans were picked from the agar culture plate with a loop and inoculated into sterile broth medium. The culture was shaken at 30°C and 200 rpm overnight. The OD value was adjusted to 0. 600 =0.03-0.06, and then diluted 10 times with YM broth culture medium to obtain the Candida albicans standby bacterial suspension.

[0071] (2) Preparation of Cryptococcus neoformans suspension

[0072] Several single colonies were picked from the agar culture plate with a loop and inoculated into SDB broth (glucose, 20.00 g / L; a mixture of equal amounts of animal tissue pepsin hydrolysate and trypticase), and the OD600 was adjusted to 0.03-0.06 with SDB medium to obtain a Cryptococcus neoformans suspension.

[0073] (3) Preparation of Trichophyton mentagrophytes suspension

[0074] Select a strain with good growth, add 10mL of 0.85% sterile sodium chloride injection, and gently blow several times with a Pasteur pipette. Take the conidia suspension and let it stand for a while. Take the upper layer and count it with a hemocytometer. Use potato dextrose liquid medium (PDB) to adjust the suspension concentration to (2-6)×10 5 CFU / mL, and the ready-to-use suspension of Trichophyton mentagrophytes is obtained.

[0075] 3. Antifungal activity assay

[0076] (1) The antifungal activities of the aryldihydronaphthalene-type lignan analogs 2-5 synthesized in Examples 1-4 against Candida albicans (C. albicans) and Cryptococcus neoformans (C. neoformans) were determined in liquid culture medium.

[0077] The prepared Candida albicans and Cryptococcus neoformans suspensions were added to a 96-well culture plate at a volume of 195 μL / well, and then 5 μL of DMSO solutions of aryldihydronaphthalene-type lignan analogs 2-5 at different concentrations were added to each well; the total volume of each well was 200 μL, fluconazole was set as the positive control group at a concentration of 20 μg / mL, and DMSO was set as the negative control group. Three replicates were set for each treatment, and a blank control group containing only culture medium without bacteria was set at the same time. The plates were placed in an incubator at 30°C and 200 rpm for 24 h, and then the OD600 value was determined using an enzyme analyzer. Three parallel experiments were performed for each compound, and the data were processed using GraphPadPrism 5. The experimental data are shown in Table 1.

[0078] (2) The antifungal activity of the aryldihydronaphthalene-type lignan analogs 2-5 synthesized in Examples 1-4 against Trichophyton mentagrophytes (T. mentagrophytes) was determined in liquid culture medium.

[0079] A stock suspension of Trichophyton mentagrophytes was diluted 100-fold with PDB liquid medium and then added to a 96-well plate. 5 μL of a DMSO solution of aryldihydronaphthalene-type lignan analogs 2-5 was then added. Ketoconazole served as a positive control, and DMSO served as a blank control. Three replicate wells were plated for each compound, incubated at 30°C for 3 days, and absorbance was measured at 600 nm. Three replicates were performed for each compound, and data were processed using GraphPad Prism 5. The experimental data are shown in Table 1.

[0080] Table 1 Antifungal test results of compounds 2-5

[0081] Compound C.albicans / μΜ C.neoformans / μΜ T.mentagrophytes / μΜ DMSO 0 0 0 Fluconazole 42.52 45.22 - Ketoconazole - - 48.40 Compound 1 34.28 - 39.63 Compound2 - 32.54 40.25 Compound3 33.16 41.25 - Compound4 40.89 - - Compound5 28.96 17.13 41.35

[0082] As shown in Table 1, aryldihydronaphthalene lignan analogues 1, 3, 4, and 5 all have certain antibacterial activity against Candida albicans (C.albicans), compound 2 has certain antibacterial activity against Cryptococcus neoformans (C.neoformans) and Trichophyton mentagrophytes (T.mentagrophytes), and compound 5 has good antibacterial activity against these three fungi. Its IC 50 The results show that the synthetic aryl dihydronaphthalene lignan analogues of the present invention have good antibacterial activity and have certain application prospects in the development of corresponding drugs.

[0083] The above description is a detailed description of the preferred embodiments of the present invention, but the embodiments are not intended to limit the scope of the patent application of the present invention. Any equivalent changes or modifications completed under the technical spirit suggested by the present invention should fall within the patent scope covered by the present invention.

Claims

1. An aryldihydronaphthalene-type lignan analogue with antibacterial activity, characterized in that: The aryldihydronaphthalene-type lignan analog is a compound having a structure of formula (I), or a pharmaceutically acceptable prodrug thereof; Wherein, R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen, hydroxyl, aldehyde, amino, acetyl, carboxyl, cyano, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, substituted or unsubstituted 5-10 membered aryl or 5-10 membered heteroaryl.

2. The aryldihydronaphthalene-type lignan analogue with antibacterial activity according to claim 1 is characterized in that The aryldihydronaphthalene-type lignan analog is compound 2-5 or a pharmaceutically acceptable prodrug thereof; 3. The method for preparing an aryldihydronaphthalene-type lignan analogue according to any one of claims 1 or 2, characterized in that: The following steps are involved: (1) Sesamin ether bond is opened to prepare compound 2: Sesamin was dissolved in a mixture of dichloromethane and acetic anhydride, cooled to 0°C, and AlCl3 was added. The reaction was continued for 2-3 hours, and then a saturated sodium bicarbonate solution was added to quench the reaction. The mixture was extracted with dichloromethane and purified by silica gel column chromatography to obtain compound 2. (2) Deacetylation to prepare compound 3: Compound 2 was dissolved in methanol, potassium carbonate and water were added, and the mixture was reacted at room temperature for 2-3 hours. Methanol and water were removed under reduced pressure, and dichloromethane was added to dissolve the mixture. Potassium carbonate was removed by filtration, and the filtrate was concentrated to obtain a crude product. The crude product was purified by silica gel column to obtain compound 3; (3) Dess-Martin oxidation to prepare compound 4: Compound 3 was dissolved in dichloromethane, sodium bicarbonate was added at 0°C, and the mixture was stirred for 5-10 minutes. Dess-Martin oxidant was then slowly added in batches and the reaction was continued at 0°C for 2-3 hours. After the reaction was completed, water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic phase was purified by silica gel column chromatography to obtain compound 4; (4) Preparation of Compound 5 Compound 3 was dissolved in acetonitrile, sodium bicarbonate was added at 0°C, and the mixture was stirred for 5-10 minutes. Dess-Martin oxidant was then slowly added in batches, and the mixture was heated to room temperature for 2-3 hours. After the reaction, water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic phase was purified by silica gel column chromatography to obtain compound 5.

4. The preparation method according to claim 3, wherein: The molar ratio of sesamin to AlCl3 in step (1) is 1:1.2, and the volume ratio of dichloromethane to acetic anhydride is 2:

1.

5. The preparation method according to claim 3, wherein: In step (2), the molar ratio of compound 2 to potassium carbonate is 1:2, and the volume ratio of methanol to water is 10:

1.

6. The preparation method according to claim 3, wherein: The molar ratio of compound 3, sodium bicarbonate and Dess-Martin oxidant in step (3) is 1:3:1.

5.

7. The preparation method according to claim 3, wherein: The molar ratio of compound 3, sodium bicarbonate and Dess-Martin oxidant in step (4) is 1:4:2.

4.

8. Use of the aryldihydronaphthalene-type lignan analogue according to any one of claims 1 or 2 in the preparation of antibacterial drugs.

9. The use according to claim 8, characterized in that The fungi are Candida albicans, Cryptococcus neoformans and Trichophyton mentagrophytes.

10. A pharmaceutical composition comprising the aryldihydronaphthalene lignan analogue according to any one of claims 1 or 2 or a pharmaceutically acceptable isomer, solvate thereof and a pharmaceutically acceptable carrier or excipient.

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