Tetrahydrooxazoloisoindolinone compounds, electrochemical synthesis method and application thereof

Abstract

This invention provides a tetrahydrooxazolonesoindolone compound and its para-electrocatalytic preparation method. Using N-vinyl o-phenylimine and alcohols as raw materials, this invention successfully achieved the efficient construction of a series of tetrahydrooxazolonesoindolone compounds through a para-electrocatalytic strategy. In vitro antibacterial and antifungal activity studies showed that tetrahydrooxazolonesoindolones possessed certain inhibitory activity against the tested bacteria and fungi. Compound I-12 exhibited good broad-spectrum antibacterial bioactivity, with a MIC value of 8-32 µg·mL. ‑1 Its activity against methicillin-resistant Staphylococcus aureus (MRSA) is comparable to that of chloramphenicol and norfloxacin. Structure-activity relationship studies show that the introduction of the F atom can improve the molecule's antibacterial activity.

Description

Technical Field

[0001] This invention relates to the field of chemical technology, specifically to a tetrahydrooxazolone isoindolone compound, its para-electrocatalytic preparation method, and its application in antimicrobial activity. Background Technology

[0002] Isoindolinone ring systems, as an important class of bioactive skeletons, are widely found in various natural products and drug molecules, and have significant application value in the development of sedatives, hypnotics, and muscle relaxants. Currently, the construction of this structural fragment is mainly achieved through amide alkylation processes catalyzed by transition metal complexes, superacids, Lewis acids / Brønsted acids, or thiourea derivatives (J. Chem. Soc., Perkin Trans. 2000, 1, 1715; Adv. Synth. Catal. 2014, 356, 2627). On the other hand, tetrahydrooxazole structural fragments are also widely found in various natural products, drugs, and pesticide molecules, and have important application value. Studies have shown that compounds containing both isoindolinone and tetrahydrooxazole fragments exhibit important activity in inhibiting HIV-1 reverse transcriptase. However, current research on the synthesis of such heterocyclic systems is still relatively limited, restricting further exploration of their activity and drug development. For example, Chinese patent CN118005650A discloses a photocatalytic method for synthesizing tetrahydrooxazozonoisoindololinones; Professor Guo Chang's research group at the University of Science and Technology of China reported a nickel-catalyzed anodic oxidation strategy, which generates heterocyclic radical cationic intermediates such as indole, pyrrole, and furan through electrochemical single-electron oxidation and combines them with α-carbonyl radical species bound to a chiral catalyst, realizing the asymmetric cross-dehydrogenation heteroarylation reaction of carbonyl α-position CH / CH (Angew. Chem. Int. Ed., 2024, e202415723). Therefore, developing new and efficient methods for constructing tetrahydrooxazozonoisoindololinone compounds is of significant research importance.

[0003] Organic electrochemistry, as an important branch of synthetic chemistry, has attracted much attention in recent years. Based on the different roles of the electrodes in the reaction, organic electrocatalysis can be divided into two types: single-electrode catalysis and para-electrocatalysis. In single-electrode catalysis, only one electrode participates in the target reaction. However, the reaction is often accompanied by side reactions such as hydrogen evolution or sacrificial anodes, leading to the consumption or generation of additional substances. From the perspective of green chemistry, its atom economy is poor. Furthermore, the theoretical upper limit of the Faraday efficiency of this method is 100%. In contrast, para-electrocatalysis utilizes both the cathode and anode as working electrodes for the target reaction, avoiding the net consumption or generation of additional substances, thus offering advantages in energy and atom economy. However, para-electrocatalysis also faces challenges: oxidized and reduced intermediates existing simultaneously in the electrolytic cell are prone to decomposition or side reactions; simultaneously, the mass transfer efficiency of reactants between the anode and cathode is often low. These factors collectively restrict the rapid development of para-electrocatalysis technology. Therefore, developing efficient, green, and concise novel electrochemical methods to achieve the precise construction of important molecules has significant research value. Summary of the Invention

[0004] The purpose of this invention is to provide a tetrahydrooxazoloindolineone compound, its para-electrocatalytic preparation method, and its application.

[0005] The technical solution adopted in this invention is as follows:

[0006] In a first aspect, the present invention provides a tetrahydrooxazolonesoindolone compound, characterized in that the structure of the tetrahydrooxazolonesoindolone I is as follows:

[0007]

[0008] Among them, R1 is selected from C1-C 20 Alkyl, C6-C 14 Aryl, C6-C 14 Oxyheterocycles, C6-C 14 Nitrogen heterocycles, C6-C 14 Sulfur heterocycles, C3-C 20 oxygen heterochain, C3-C 20 Nitrogen heterochains and C3-C 20 Any of the sulfur heterochains; the C1-C 20 Alkyl groups include C1-C 20 Straight-chain or branched alkyl groups, C3-C 16 cycloalkyl; C1-C 20 The straight-chain or branched alkyl group may also contain substituents, preferably phenyl or F.

[0009] R2 is one or more substitutions at any position on the benzene ring, and R2 is selected from hydrogen, C1-C... 20 Chain alkyl, C3-C16 cycloalkyl, C4-C 16 Heterocyclic groups containing N, O, or S, C6-C 24 The aryl group, substituents containing C, N, O, S, P or halogens, are C6-C. 24 It is any one of the substituted aryl group and halogen. The halogen is selected from F, Cl, etc.

[0010] Secondly, the present invention provides a method for preparing the aforementioned tetrahydrooxazolonesisoindolone, comprising the following steps:

[0011] Using N-vinyl o-benzylimine II and alcohol compound R1OH as raw materials, an electrochemical reaction was carried out in the presence of electrolyte and organic solvent using a two-electrode system to obtain tetrahydrooxazolone isoindolineone compound I.

[0012] The structure of II is as follows:

[0013]

[0014] R2 is selected from hydrogen, C1-C 20 Alkyl, C3-C 16 cycloalkyl, C4-C 16 Heterocyclic groups containing N, O, or S, C6-C 24 The aryl group, substituents containing C, N, O, S, P or halogens, are C6-C. 24 Any of the substituted aryl groups; the C1-C 20 Alkyl groups include C1-C 20 Straight-chain or branched alkyl groups, C3-C 16 cycloalkyl; C1-C 20 The straight-chain or branched alkyl group may also contain substituents, preferably phenyl or F.

[0015] Wherein, the alcohol compound has the structural formula R1OH, and R1 is selected from C1-C1. 20 Alkyl, C6-C 14 Aryl, C6-C 14 Oxyheterocycles, C6-C 14 Nitrogen heterocycles, C6-C 14 Sulfur heterocycles, C3-C 20 oxygen heterochain, C3-C 20 Nitrogen heterochains and C3-C 20 Any of the sulfur heterochains; the C1-C 20 Alkyl groups include C1-C 20 Straight-chain or branched alkyl groups, C3-C 16 cycloalkyl; C1-C 20 The straight-chain or branched alkyl group may also contain substituents, preferably phenyl or F.

[0016] Optionally, the alcohol compound is selected from any one of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, cyclopentanol, cyclohexanol, glycol, ethylene glycol monomethyl ether, propylene glycol, glycerol, benzyl alcohol, allyl alcohol, 2,2-difluoroethanol, 2,2,2-trifluoroethanol, difluoropropanol, trifluoropropanol, hexafluoroisopropanol, and various substituent-containing variants thereof.

[0017] Optionally, the electrolyte is selected from any one of tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide iodide, hexadecyltrimethylammonium bromide, tetraethylammonium bromide, potassium bromide, sodium bromide, and lithium bromide; preferably, the electrolyte is tetra-n-butylammonium bromide.

[0018] Optionally, the organic solvent is selected from toluene, dichloromethane, 2-methyltetrahydrofuran, 1,4-dioxane, methyl tert-butyl ether, benzene, tetrahydrofuran, diethyl ether, acetonitrile, acetone, 1,2-dichloroethane, ethylene glycol dimethyl ether, dimethylformamide, dimethyl sulfoxide, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, cyclopentanol, cyclohexanol, glycol, ethylene glycol monomethyl ether, propylene glycol, glycerol, benzyl alcohol, allyl alcohol, 2,2-difluoroethanol, 2,2,2-trifluoroethanol, difluoropropanol, trifluoropropanol, hexafluoroisopropanol, and various variants thereof containing substituents.

[0019] Optionally, the volume percentage of alcohol compounds in the organic solvent is 15% to 100%; preferably, the alcohol compounds serve as both reactants and solvents, i.e., the organic solvent in the reaction system is an alcohol compound.

[0020] Optionally, the concentration of N-vinyl o-benzylimine II in the reaction system is 0.05 mol / L.

[0021] Optionally, the molar ratio of N-vinyl o-benzylimine II to the electrolyte is 1:1.

[0022] Optionally, in the two-electrode system, the anode electrode is selected from a platinum electrode or a carbon electrode, preferably a platinum electrode; the cathode electrode is selected from any one of a mesh glassy carbon (RVC) electrode, a metal foam electrode such as nickel foam, a metal electrode such as iron, zinc, aluminum, or copper, or a carbon electrode, preferably an RVC electrode or a nickel foam electrode, more preferably an RVC electrode.

[0023] Optionally, the reaction temperature during the reaction process is 10-70°C. o C; Preferably, the reaction temperature is 30 °C.

[0024] Optionally, the reaction time should be 1-24 hours; preferably, the reaction time is 2 hours.

[0025] Optionally, the reaction is constant current electrolysis with a current of 5-30 mA; preferably, the current is 10-20 mA.

[0026] This invention utilizes N-vinyl-o-phenylimine and alcohol compounds as raw materials, with a platinum electrode as the anode and an RVC electrode as the cathode, to construct a series of tetrahydrooxazolonesisoindolone compounds via para-electrocatalysis. In vitro antibacterial and antifungal activity studies showed that the tetrahydrooxazolonesisoindolone compounds exhibited certain inhibitory activity against the tested bacteria and fungi. Compound I-12 demonstrated good broad-spectrum antibacterial bioactivity, with a MIC value of 8-32 µg·ml. -1 Its activity against methicillin-resistant Staphylococcus aureus (MRSA) is comparable to that of chloramphenicol and norfloxacin. Structure-activity relationship studies show that the introduction of the F atom can improve the molecule's antibacterial activity.

[0027] The present invention further provides the application of the tetrahydrooxazoloindolineone I in the preparation of antibacterial drugs.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] This invention provides a tetrahydrooxazolobenzinoindolone compound and its para-electrocatalytic preparation method. The method uses readily available and inexpensive N-vinyl o-phenylimine and alcohols as raw materials, with a platinum electrode as the anode and an RVC electrode as the cathode, to construct a series of tetrahydrooxazolobenzinoindolone compounds via para-electrocatalysis. This method is highly efficient and environmentally friendly, possessing advantages such as high efficiency, simple operation, and mild reaction conditions, and has significant application prospects. The tetrahydrooxazolobenzinoindolone compounds provided by this invention also exhibit antibacterial activity, providing a research foundation for the development of antibacterial drugs. Attached Figure Description

[0030] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0031] Figure 1 This is the hydrogen NMR spectrum of I-1 in Example 1 of the present invention.

[0032] Figure 2 This is the carbon spectrum of I-1 in Example 1 of the present invention. Detailed Implementation

[0033] The present invention will now be described in detail with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present invention, but do not limit the invention in any way. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention. These all fall within the scope of protection of the present invention.

[0034] Taking compound I-1 as an example, screening studies were conducted on electrode, electrolyte, current and other conditions.

[0035]

[0036]

[0037] Example 1

[0038] This embodiment provides a tetrahydrooxazoloindolineone compound and its para-electrocatalytic preparation method:

[0039]

[0040] To a 10 mL electrolytic cell containing a magnetic induction electrode, a platinum electrode (anode, 15 mm x 15 mm x 0.1 mm), and an RVC electrode (cathode, 15 mm x 15 mm x 1 mm), compound II (0.3 mmol, 1.0 eq), tetrabutylammonium bromide (0.3 mmol, 1.0 eq), and an alcohol compound (6.0 mL) were added sequentially, followed by purging with nitrogen three times. The mixture was then heated at 30 °C. o C was electrolyzed at a constant current of 20 mA. After the reaction was completed as detected by TLC plate, the reaction solution was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1, V / V) to obtain product I.

[0041]

[0042] White solid; 44.9 mg (73%); Eluent: petroleum ether / EtOAc = 5:1; 1 H-NMR(400 MHz, CDCl3) δ 7.82 (d, J = 7.4 Hz, 1H), 7.66-7.60 (m, 2H), 7.59-7.55 (m,1H), 6.05 (s, 1H), 5.27 (dd, J = 5.9, 4.8 Hz, 1H), 4.59 (dd, J = 9.5, 6.0 Hz, 1H), 4.06 (dd, J = 9.5, 4.8 Hz, 1H), 3.56 (s, 3H);13 C NMR (100 MHz, CDCl3) δ172.7, 142.4, 133.5, 132.6, 130.9, 124.9, 124.3, 90.5, 85.9, 76.7, 56.6.

[0043]

[0044] White solid; 37.1 mg (53%); Eluent: petroleum ether / EtOAc = 10:1 to 5:1; 1 H-NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.5 Hz, 1H), 7.65-7.59 (m, 2H), 7.58-7.54 (m, 1H), 6.05 (s, 1H), 5.36 (dd, J = 5.9, 4.8 Hz, 1H), 4.58 (dd, J = 9.5, 5.9 Hz, 1H), 4.08 (dd, J = 9.4, 4.8 Hz, 1H), 3.80 (dt, J = 9.5, 6.8Hz, 1H), 3.66 (dt, J = 9.5, 6.7 Hz, 1H), 1.72-1.63 (m, 2H), 0.95 (t, J = 7.4Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 172.6, 142.5, 133.4, 132.7, 130.8, 124.9,124.2, 90.5, 84.5, 76.8, 71.0, 22.8, 10.7.

[0045]

[0046] White solid; 54.6 mg (73%); Eluent: petroleum ether / EtOAc = 5:1; 11H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.5 Hz, 1H), 7.63 - 7.58 (m, 2H), 7.56 - 7.52 (m, 1H), 6.05 (s, 1H), 5.37 (t, J = 5.5 Hz, 1H), 4.59 (dd, J = 9.6, 6.0 Hz, 1H), 4.14 (dd, J = 9.6, 5.0 Hz, 1H), 4.01 - 3.96 (m, 1H), 3.90 - 3.85 (m, 1H), 3.65 - 3.56 (m, 2H), 3.39 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 172.6, 142.4, 133.5, 132.4, 130.8, 124.8, 124.2, 90.4, 84.7, 76.6, 71.4, 68.4, 59.1.

[0047]

[0048] Colorless oil; 45.2 mg (61%); Eluent: petroleum ether / EtOAc = 5:1; 1 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.4 Hz, 1H), 7.64 - 7.59 (m, 2H), 7.57 - 7.53 (m, 1H), 6.06 (s, 1H), 5.48 (dd, J = 5.9, 4.8 Hz, 1H), 4.56 (dd, J = 9.4, 6.0 Hz, 1H), 4.15 (hept, J = 6.2 Hz, 1H), 4.04 (dd, J = 9.4, 4.8 Hz, 1H), 1.29 (d, J = 6.1 Hz, 3H), 1.24 (d, J = 6.2 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 172.6, 142.4, 133.4, 132.7, 130.8, 124.9, 124.2, 90.5, 84.6, 76.8, 75.9, 28.4, 19.5.

[0049]

[0050] Colorless oil; 37.5 mg (49%); Eluent: petroleum ether / EtOAc = 5:1; 1 H NMR(400 MHz, CDCl3) δ 7.82 (dt, J = 7.4, 1.1 Hz, 1H), 7.71-7.53 (m, 3H), 6.08(s, 1H), 5.41 (dd, J = 6.0, 4.9 Hz, 1H), 4.64 (dd, J = 9.7, 5.9 Hz, 1H), 4.14(dd, J = 9.7, 4.9 Hz, 1H), 4.11-3.91 (m, 2H); 13 C NMR (100 MHz, CDCl3) δ172.6, 142.4, 133.4, 132.7, 130.8, 124.9, 124.2, 90.5, 84.6, 76.8, 75.9,28.4, 19.5.

[0051]

[0052] Colorless oil; 30.3 mg (37%); Eluent: petroleum ether / EtOAc = 10:1; 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.5 Hz, 1H), 7.70-7.55 (m, 3H), 6.09 (s, 1H), 5.46 (dd, J = 5.9, 4.9 Hz, 1H), 4.66 (dd, J = 9.8, 6.0 Hz, 1H), 4.24-4.11 (m,3H). 19 F NMR (376 MHz, CDCl3) δ -74.09; 13 C NMR (101 MHz, CDCl3) δ 172.7,142.4, 133.9, 132.0, 131.1, 125.1, 124.5, 90.6, 85.3, 76.4, 66.0 (q, J = 34.8Hz).

[0053]

[0054] White solid; 25.1 mg (36%); Eluent: petroleum ether / EtOAc = 10:1; 11H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.4 Hz, 1H), 7.64 - 7.59 (m, 2H), 7.57 - 7.53 (m, 1H), 6.06 (s, 1H), 5.48 (dd, J = 5.9, 4.8 Hz, 1H), 4.56 (dd, J = 9.4, 6.0 Hz, 1H), 4.15 (hept, J = 6.2 Hz, 1H), 4.04 (dd, J = 9.4, 4.8 Hz, 1H), 1.29 (d, J = 6.1 Hz, 3H), 1.24 (d, J = 6.2 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 172.6, 142.5, 133.4, 132.7, 130.8, 124.8, 124.2, 90.5, 82.5, 77.1, 70.6, 23.3, 21.5.

[0055]

[0056] Colorless oil; 28.0 mg (36%); Eluent: petroleum ether / EtOAc = 5:1; 1 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.5 Hz, 1H), 7.66 - 7.58 (m, 2H), 7.56 (ddd, J = 7.4, 6.0, 2.5 Hz, 1H), 6.05 (s, 1H), 5.42 (dd, J = 6.0, 4.8 Hz, 1H), 4.56 (dd, J = 9.4, 5.9 Hz, 1H), 4.43 (tt, J = 6.2, 3.8 Hz, 1H), 4.03 (dd, J = 9.4, 4.8 Hz, 1H), 2.04 - 1.81 (m, 2H), 1.76 - 1.67 (m, 4H), 1.62 - 1.50 (m, 2H); 13 13C NMR (100 MHz, CDCl3) δ 172.5, 142.5, 133.4, 132.8, 130.8, 124.8, 124.2, 90.5, 83.2, 80.3, 77.0, 33.1, 32.0, 23.7, 23.6.

[0057]

[0058] White solid; 51.8 mg (63%); Eluent: petroleum ether / EtOAc = 10:1-5:1-3:1; 1 H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.71 (s, 1H), 5.98 (s, 1H), 5.25(t, J = 5.3 Hz, 1H), 4.58 (dd, J = 9.6, 5.9 Hz, 1H), 4.04 (dd, J = 9.5, 4.7Hz, 1H), 3.54 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 170.5, 141.4, 138.2, 135.8, 132.3, 126.7, 126.6, 89.5, 86.1, 76.8, 56.8.

[0059]

[0060] White solid; 54.7 mg (76%); Eluent: petroleum ether / EtOAc = 5:1; 1 H NMR(400 MHz, CDCl3) δ 7.70 (d, J = 7.3 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.51(t, J = 7.7 Hz, 1H), 6.10 (s, 1H), 5.27 (t, J = 5.3 Hz, 1H), 4.60 (dd, J =9.6, 5.8 Hz, 1H), 4.10 (dd, J = 9.6, 4.7 Hz, 1H), 3.55 (s, 3H); 13 C NMR (100MHz, CDCl3) δ 171.6, 140.2, 134.7, 133.7, 132.5, 131.0, 123.2, 89.3, 85.8,76.8, 56.6.

[0061]

[0062] White solid; 51.1 mg (71%); Eluent: petroleum ether / EtOAc = 5:1; mp 11H NMR (400 MHz, CDCl3) δ 7.64 - 7.46 (m, 3H), 5.98 (s, 1H), 5.35 – 5.24 (m, 1H), 4.58 (dd, J = 9.5, 5.9 Hz, 1H), 4.04 (dd, J = 9.5, 4.9 Hz, 1H), 3.57 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 169.2, 143.5, 133.2, 131.4, 127.5, 121.7, 88.0, 85.1, 75.3, 55.6.

[0063]

[0064] White solid; 45.6 mg (63 %); Eluent: petroleum ether / EtOAc = 5:1; m.p. 1 1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 8.5, 7.0 Hz, 1H), 7.43 (dd, J = 8.6, 6.6 Hz, 1H), 5.97 (s, 1H), 5.24 (dd, J = 5.9, 4.7 Hz, 1H), 4.58 (dd, J = 9.6, 5.9 Hz, 1H), 4.05 (dd, J = 9.6, 4.8 Hz, 1H), 3.54 (s, 3H). 19 19F NMR (376 MHz, CDCl3) δ -127.06 (d, J = 11.2 Hz, 1F), -131.8 (d, J = 11.2 Hz, 1F); 13 13C NMR (100 MHz, CDCl3) δ 170.8 (d, J = 2.9 Hz), 154.7 (dd, J = 154.1, 14.0 Hz), 152.1 (dd, J = 150.7, 14.1 Hz), 139.0 (dd, J = 7.8, 3.3 Hz), 129.2 (dd, J = 6.7, 3.1 Hz), 113.90 (dd, J = 19.0, 2.0 Hz), 113.8 (d, J = 20.0 Hz), 89.6 (d, J = 2.1 Hz), 86.0, 78.8, 56.7.

[0065]

[0066] White solid; 46.2 mg (45%); Eluent: petroleum ether / EtOAc = 5:1; 1 H NMR (400 MHz, CDCl3) δ 5.51 (dd, J = 7.3, 4.5 Hz, 1H), 4.43 (dd, J = 10.1, 7.2Hz, 1H), 4.27 (dd, J = 10.1, 4.5 Hz, 1H), 3.91 (s, 3H), 3.53 (s, 3H); 13 C NMR(100 MHz, CDCl3) δ 170.8 (d, J = 2.9 Hz), 154.7 (dd, J = 154.1, 14.0 Hz), 152.1 (dd, J = 150.7, 14.1 Hz), 139.0 (dd, J = 7.8, 3.3 Hz), 129.2 (dd, J =6.7, 3.1 Hz), 113.90 (dd, J = 19.0, 2.0 Hz), 113.8 (d, J = 20.0 Hz), 89.6 (d,J = 2.1 Hz), 86.0, 78.8, 56.7.

[0067]

[0068] White solid; 43.4 mg (66%); Eluent: petroleum ether / EtOAc = 5:1; 1 H NMR (400 MHz, CDCl3) δ 7.75 -7.57 (m, 1H), 7.53-7.31 (m, 2H), 6.00 (d, J = 3.9Hz, 1H), 5.25 (dd, J = 5.9, 4.8 Hz, 1H), 4.58 (ddd, J = 9.6, 5.9, 3.8 Hz, 1H), 4.05 (dd, J = 9.5, 4.8 Hz, 1H), 3.56 (s, 3H), 2.46 (d, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.9, 172.8, 144.6, 142.9, 141.3, 139.8, 134.4,132.8, 131.8, 129.9, 125.1, 124.8, 124.7, 124.0, 90.4, 85.9, 85.9, 77.4,76.7, 76.6, 56.6, 56.6, 22.1, 21.6.

[0069]

[0070] White solid; 54.6 mg (76%); Eluent: petroleum ether / EtOAc = 5:1; 1 H NMR(400 MHz, CDCl3) δ 7.83-7.70 (m, 1H), 7.62-7.59 (m, 1H), 7.55 (dt, J = 8.1,1.7 Hz, 1H), 6.01 (d, J = 4.3 Hz, 1H), 5.27 (dd, J = 5.9, 4.7 Hz, 1H), 4.59(ddd, J = 9.6, 5.9, 4.9 Hz, 1H), 4.06 (dd, J = 9.5, 4.8 Hz, 1H), 3.56 (s,3H). 13 C NMR (100 MHz, CDCl3) δ 171.6, 171.3, 144.0, 140.6, 140.0, 137.2,134.5, 133.6, 131.4, 131.0, 126.1, 125.6, 125.1, 124.9, 90.0, 89.8, 86.0,86.0, 76.8, 76.7, 56.7, 56.7.

[0071] Example 2

[0072] Antimicrobial activity study

[0073] The compound solution was diluted to a concentration range of 0.5–512 μg / mL, with three replicates for each concentration. The prepared bacterial cultures were inoculated into culture media containing different concentrations of the target compound. After gentle mixing, the culture plates were incubated at 37°C. Mueller-Hinton broth was used as the bacterial culture medium. The bacterial inoculum concentration was 1 × 10⁻⁶. 6 CFU / mL; the fungal culture medium was Sabouraud dextrose agar, and the fungal inoculum concentration was 1×10⁻⁶.5 Spores / mL. After culturing for another 18 hours using a microplate reader, the optical density (OD) of each well was measured at a wavelength of 600 nm. 600 Using uninoculated culture medium as a blank control, the inhibition rate of each well was calculated. The MIC value was defined as the lowest drug concentration with an inhibition rate ≥90%.

[0074] The results of the in vitro antibacterial activity tests of the compounds are summarized in Tables 1, 2, and 3. Fluconazole (a potent antifungal drug), norfloxacin (a broad-spectrum quinolone antibiotic), and chloramphenicol (a classic antibiotic for treating superficial bacterial infections) were used as positive control drugs. These three drugs cover fungal inhibition, Gram-negative / positive bacteria targeting, and multi-mechanism antibacterial activity, respectively. Their selection takes into account the differences in antibacterial spectrum and the diversity of mechanisms of action, enabling a comprehensive evaluation of the antibacterial potential of the target compounds.

[0075] In vitro antibacterial and antifungal activity results showed that the tetrahydrooxazolonesinoindolone compounds possessed certain in vitro antibacterial and antifungal activities, as detailed in the table. Among them, compound I-9 exhibited strong antibacterial activity, particularly showing good inhibitory effects against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, with a MIC value of 8 µg·ml. -1 This result indicates that introducing an F atom into the oxazoloisindole skeleton helps enhance the antibacterial activity of the compound, which warrants further investigation. Compound I-15 showed some inhibitory activity against the fungus Candida albicans, while other target compounds did not exhibit significant antifungal activity.

[0076] Table 1. In vitro antibacterial and antifungal activity studies of the compounds (MIC µg·ml⁻¹)

[0077]

[0078] Table 2. In vitro antibacterial and antifungal activity studies of the compounds (MIC µg·ml⁻¹)

[0079]

[0080] Table 3. In vitro antibacterial and antifungal activity studies of the compounds (MIC µg·ml⁻¹)

[0081]

[0082] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A tetrahydrooxazolonesoindolone compound, characterized in that, The structure of the tetrahydrooxazoloindolineone compound is shown in Formula I below: ， Among them, R1 is selected from C1-C 20 Alkyl, C6-C 14 Aryl, C6-C 14 Oxyheterocycles, C6-C 14 Nitrogen heterocycles, C6-C 14 Sulfur heterocycles, C3-C 20 oxygen heterochain, C3-C 20 Nitrogen heterochains and C3-C 20 Any of the sulfur heterochains; R2 is selected from hydrogen, C1-C 20 Chain alkyl, C3-C 16 cycloalkyl, C4-C 16 Heterocyclic groups containing N, O, or S, C6-C 24 The aryl group, substituents containing C, N, O, S, P or halogens, are C6-C. 24 It can be any one of the substituted aryl groups or halogens.

2. The method for preparing the tetrahydrooxazolone isoindolone compound according to claim 1, characterized in that, Includes the following steps: Using N-vinyl o-phenylimine and alcohol compounds as raw materials, an electrochemical reaction was carried out in the presence of electrolyte and organic solvent using a two-electrode system to obtain compound I; The structure of the N-vinyl o-phenylimine is shown in Formula II below: ， R2 is selected from hydrogen, C1-C 20 Chain alkyl, C3-C 16 cycloalkyl, C4-C 16 Heterocyclic groups containing N, O, or S, C6-C 24 The aryl group, substituents containing C, N, O, S, P or halogens, are C6-C. 24 It can be any one of the substituted aryl groups or halogens.

3. The preparation method according to claim 2, characterized in that, The alcohol compound has the structural formula R1OH, wherein R1 is selected from C1-C1. 20 Alkyl, C6-C 14 Aryl, C6-C 14 Oxyheterocycles, C6-C 14 Nitrogen heterocycles, C6-C 14 Sulfur heterocycles, C3-C 20 oxygen heterochain, C3-C 20 Nitrogen heterochains and C3-C 20 Any of the sulfur heterochains.

4. The preparation method according to claim 2, characterized in that, The electrolyte is selected from any one of tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide iodide, hexadecyltrimethylammonium bromide, tetraethylammonium bromide, potassium bromide, sodium bromide, and lithium bromide.

5. The preparation method according to claim 2, characterized in that, The organic solvent is selected from toluene, dichloromethane, 2-methyltetrahydrofuran, 1,4-dioxane, methyl tert-butyl ether, benzene, tetrahydrofuran, diethyl ether, acetonitrile, acetone, 1,2-dichloroethane, ethylene glycol dimethyl ether, dimethylformamide, dimethyl sulfoxide, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, cyclopentanol, cyclohexanol, glycol, ethylene glycol monomethyl ether, propylene glycol, glycerol, benzyl alcohol, allyl alcohol, 2,2-difluoroethanol, 2,2,2-trifluoroethanol, difluoropropanol, trifluoropropanol, hexafluoroisopropanol, and various variants thereof containing substituents.

6. The preparation method according to claim 2, characterized in that, In the two-electrode system, the anode electrode is selected from platinum electrode or carbon electrode; the cathode electrode is selected from any one of mesh glassy carbon, foamed nickel, iron, zinc, aluminum, copper, and carbon electrode.

7. The preparation method according to claim 2, characterized in that, The electrochemical reaction is performed by a constant current deposition method, and the current is 5-30 mA.

8. The preparation method according to claim 2, characterized in that, The reaction temperature is 10-70 ℃.

9. The preparation method according to claim 2, characterized in that, The reaction time is 1-24 hours.

10. The use of the tetrahydrooxazoloindoline ketone compound of claim 1 in the preparation of antibacterial drugs.

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