Isoxazoline-hybridized lignan compounds, methods of making and uses thereof

Abstract

The application discloses an isoxazoline hybrid lignan compound and a preparation method and application thereof. The lignan compound in the application is one of isoxazoline magnolol, isoxazoline and magnolol, isoxazoline nitrated magnolol, isoxazoline nitrated and magnolol derivatives, and has the following chemical general formula: The application takes one of magnolol, honokiol, nitrated magnolol or nitrated and magnolol as a raw material, takes triethylamine as a base, dichloromethane as a solvent, makes the raw material react with alpha-chloro oxime, and obtains the isoxazoline hybrid lignan compound. The compound has good insecticidal activity on Plutella xylostella Linnaeus and Mythimna separata Walker, can be used for preparing high-efficiency insecticides, and is applied to the prevention and treatment of Plutella xylostella and Mythimna separata.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of agricultural insecticide, in particular to a new isoxazoline hybrid lignan compound and a preparation method and application thereof. BACKGROUND

[0002] Honokiol and Magnolol are new lignans from Magnolia officinalis Rehd. et Wils. or Magnolia officinalis Rehd. et Wils var. biloba Rehd. et Wils. They have attracted much attention due to their insecticidal, antibacterial, antiviral and antitumor activities. Literature [Ye YH, Li C, Yang J, et al. Construction of an immobilised acetylcholinesterase column and its application in screening insecticidal constituents from Magnolia officinalis. Pest Management Science, 2016, 71(4): 607-615] and [Guo M Y, Chen Y G, Wang X F, et al. Application effect of biopesticides in the control of tobacco and cotton pests. Tobacco Science and Technology, 2020, 53(7): 19-25] reported the insecticidal activity of honokiol and magnolol against brown planthopper, cotton bollworm, armyworm, tobacco aphid and cabbage worm. Literature [Shirui R, Yingming Y, Mengying X, et al. A Chinese herb preparation, honokiol, inhibits Streptococcus mutans biofilm formation. Archives of Oral Biology, 2023, (147): 105610-105610], [Liu T, Pan Y L, Lai R F, et al. New mechanism of magnolol and honokiol from Magnolia officinalis against Staphylococcus aureus. Natural Product Communications, 2014, 9(9): 1307-1309] and [Sun L M, Kai L, et al. The effect of honokiol on ergostero biosynthesis and vacuole function in Candida albicans. Microbiol. Biotechnol, 2020, 30(12): 1835-1842] reported that honokiol and magnolol had good antibacterial activity.The document [Franck A, Baskaran G, Benjamin L, et al. Synthesis, cytotoxicity, and antiviral activities of new neolignans related to honokiol and magnolol. Bioorganic & Medicinal Chemistry Letters, 2007, 17(16): 4428-4431] reported that honokiol and magnolol have good anti-HIV-1 activity. The document [Zhang Mingfa, Shen Yaqin, et al. Research Progress of Pharmacological Effects and Mechanisms of Honokiol and Magnolol on Lung Cancer. Drug Evaluation Research, 2022, 45(6): 1213-1220] reported that honokiol and magnolol have obvious inhibitory effect on the proliferation of various cancer cells such as liver cancer cells (HepG2) and lung cancer cells (A549).

[0003] Although the previous literature research found that honokiol and magnolol have certain insecticidal and antibacterial agricultural activities, their biological activity is still relatively mild, and there is still a big gap from actual development and application. SUMMARY

[0004] The purpose of the present application is to solve the problem of weak insecticidal activity of honokiol and magnolol in the prior art, which cannot be applied to actual production, and to provide a new isoxazoline hybrid lignan compound and its preparation method and application.

[0005] To solve the above technical problems, the technical scheme adopted by the present application is as follows: a new isoxazoline hybrid lignan compound, the new isoxazoline hybrid lignan compound is one of isoxazoline honokiol, isoxazoline and magnolol, isoxazoline nitrated honokiol, isoxazoline nitrated and magnolol derivatives, the chemical general formula of the new isoxazoline hybrid lignan compound is as shown in formula (I):

[0006]

[0007] In formula (I), R1=OH or OMe; R2 and R3=H or OH or OMe; R4=H or NO2; Ar is any of the following:

[0008]

[0009] The application also provides a preparation method of the isoxazoline hybrid new lignan compound, which comprises the following steps: taking triethylamine as a base, dichloromethane as a solvent, allowing a raw material to react with alpha-chloro oxime through 1,3-dipolar cycloaddition to obtain the isoxazoline hybrid new lignan compound; the raw material is one of magnolol, honokiol, nitrated magnolol and nitrated honokiol.

[0010] Preferably, 1 mmol of the raw material is dissolved in 5 mL of dichloromethane, 5 mmol of triethylamine is added at 40 DEG C, 4 mmol of alpha-chloro oxime is added, the reaction progress is tracked and detected, after the reaction is completed, vacuum concentration is carried out, and the isoxazoline hybrid new lignan compound is obtained through silica gel thin layer chromatography separation.

[0011] Preferably, the alpha-chloro oxime is one of alpha-chloro benzaldoxime, alpha-chloro-4-methyl benzaldoxime, alpha-chloro-3,4-dimethyl benzaldoxime, alpha-chloro-4-isopropyl benzaldoxime, alpha-chloro-4-tert-butyl benzaldoxime, alpha-chloro-2-naphthaldehyde oxime, alpha-chloro-3-cyanobenzaldoxime, alpha-chloro-3,4-dichlorobenzaldoxime, alpha-chloro-3-fluorobenzaldoxime, alpha-chloro-4-chlorobenzaldoxime or alpha-chloro-4-bromobenzaldoxime.

[0012] The application also provides application of the isoxazoline hybrid new lignan compound in preparation of an insecticide, and the insecticide is applied to Plutella xylostella and Mythimna separata Walker.

[0013] The application has the following beneficial effects: the isoxazoline hybrid new lignan compound (isoxazoline magnolol, isoxazoline honokiol, isoxazoline nitrated magnolol and isoxazoline nitrated honokiol derivative) is prepared by taking magnolol, honokiol, nitrated magnolol or nitrated honokiol as a raw material; the isoxazoline hybrid new lignan compound has good insecticidal activity on Plutella xylostella Linnaeus and Mythimna separata Walker; some compounds (derivatives III-3, IV-4, IV-6 and VII-4) have even higher insecticidal activity on Plutella xylostella than the existing commercial plant source insecticide rotenone, have insecticidal activity equivalent to that of the chemical insecticide azocyclotin, and show strong insecticidal effect; derivative I-9 shows extremely strong stomach poison effect on Mythimna separata Walker; therefore, the isoxazoline hybrid new lignan compound (isoxazoline magnolol, isoxazoline honokiol, isoxazoline nitrated magnolol and isoxazoline nitrated honokiol derivative) can be applied to preparation of a new high-efficiency insecticide. BRIEF DESCRIPTION OF DRAWINGS

[0014] Figure 1NMR spectrum of hydrogen of compound IV-1;

[0015] Figure 2 NMR spectrum of carbon of compound IV-1. DETAILED DESCRIPTION

[0016] The present application is further illustrated in conjunction with the accompanying drawings and specific examples.

[0017] Examples 1-76

[0018] Examples 1-76 are used to prepare isoxazoline hybridized new lignan compounds I-1-11, II-1-11, III-1-11, IV-1-11, V-1-8, VI-1-8, VII-1-8 and VIII-1-8 in turn.

[0019] The preparation method is as follows: 1 mmol of raw material is dissolved in 5 mL of dichloromethane, 5 mmol of triethylamine is added at 40°C, and 4 mmol of the corresponding α-chloro oxime is added, and the reaction progress is tracked and detected. After the reaction is completed, it is concentrated under reduced pressure, and thin layer chromatography on silica gel is used for separation to obtain the desired target product. The raw materials in Examples 1-76 are one of magnolol, honokiol, nitrated magnolol or nitrated honokiol. The raw material table is shown in Table 1.

[0020] The reaction general formula is as follows:

[0021]

[0022] As shown in Table 1, R 1 , R 2 , R 3 , R 4 and Ar in compounds I-1-11, II-1-11, III-1-11, IV-1-11, V-1-8, VI-1-8, VII-1-8 and VIII-1-8 correspond to the serial numbers in the above reaction general formula.

[0023] Table 1 Isosxazoline hybridized new lignan compounds prepared in Examples 1-76

[0024]

[0025]

[0026]

[0027] The physical and chemical properties of compound I-1 are as follows:

[0028] 1) White solid, melting point 73.5-74.2°C;

[0029] 2) The NMR spectrum characteristics of the compound are as follows:

[0030] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ=7.63–7.67(m,4H,Ar-H),7.37–7.42(m,8H,Ar-H),7.20(s,1H,Ar-H),7.18(d, J=2.4Hz,1H,Ar-H),6.93(d,J=2.0Hz,1H,Ar-H),6.91(d,J=2.4Hz,1H,Ar-H),5.06–5.14(m,1H,-CH2-C H -CH2-),4.95–5.03(m,1H,-CH2-C H -CH2-),3.86(s,3H,-OCH3),3.79(s,3H,-OCH3),3.26–3.38(m,2H),3.14–3.24(m,2H),3.04–3.12(m,2H),2.85–2.95(m,2H). 13 C NMR (100MHz, CDCl3): δ=156.8,156.5,156.4,155.3,132.5,131.6,131.5,130.6,130.2,130.0,129.9,1 29.7,129.2,129.1,129.0,128.7,128.6,124.8,111.4,110.1,82.0,80.7,55.7,55.4,40.2,39.4,35.9.

[0031] 3) High-resolution mass spectrometric characteristics of the compound:

[0032] Using electrospray ionization: calcd for C 34 H 33 N2O4 + ,([M+H] + )533.2440,found 533.2446.

[0033] The physicochemical properties of compound I-2 are as follows:

[0034] 1) White solid, melting point 82.0–82.7°C;

[0035] 2) NMR spectrum characteristics of the compound:

[0036] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.56 (s, 1H, Ar-H), 7.54 (s, 2H, Ar-H), 7.52 (s, 1H, Ar-H), 7.39-7.42 (m, 1H, Ar-H), 7.38 (d, J = 2.0 Hz, 1H, Ar-H), 7.19 (s, 3H, Ar-H), 7.18 (s, 3H, Ar-H), 6.92 (d, J = 1.2 Hz, 1H, Ar-H), 6.90 (d, J = 2.0 Hz, 1H, Ar-H), 5.04-5.12 (m, 1H, -CH2-C H -CH2-), 4.93-5.00 (m, 1H, -CH2-C H -CH2-), 3.86 (s, 3H, -OCH3), 3.79 (s, 3H, -OCH3), 3.26-3.35 (m, 2H), 3.14-3.23 (m, 2H), 3.02-3.12 (m, 2H), 2.84-2.94 (m, 2H), 2.36 (s, 6H, 2x-CH3). 13 C NMR (100 MHz, CDC13): δ = 156.8, 156.5, 156.4, 155.3, 140.2, 140.1, 132.4, 121.6, 131.5, 130.6, 130.2, 129.4, 129.3, 129.2, 129.1, 128.9, 127.1, 126.9, 126.6, 124.9, 111.4, 110.0, 81.9, 80.5, 55.7, 55.4, 40.2, 39.6, 39.5, 35.9, 26.9, 21.4.

[0037] 3) The high resolution mass spectrum characteristics of the compound:

[0038] Using electrospray ionization: calcd for C 36 H 37 N2O4 + , ([M+H] + ) 561.2753, found 561.2756.

[0039] The physicochemical properties of compound I-3 are as follows:

[0040] 1) White solid, melting point 81.3-82.0°C;

[0041] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0042] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.47 (s, 1H, Ar-H), 7.44 (s, 1H, Ar-H), 7.33-7.41 (m, 4H, Ar-H), 7.19 (d, J = 7.2 Hz, 2H, Ar-H), 7.14 (s, 1H Ar-H), 7.12 (s, 1H Ar-H), 6.92 (s, 1H Ar-H), 6.90 (s, 1H Ar-H), 5.03-5.11 (m, 1H, -CH2-C H -CH2-), 4.92-5.00 (m, 1H, -CH2-C H -CH2-), 3.86 (s, 3H, -OC H 3), 3.79 (s, 3H, -OC H 3), 3.23-3.35 (m, 2H), 3.12-3.22 (m, 2H), 3.02-3.10 (m, 2H), 2.83-2.93 (m, 2H), 2.26 (s, 12H, 4 x -C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.8, 156.6, 156.5, 155.3, 138.9, 138.8, 137.0, 136.9, 132.5, 131.6, 130.6, 130.2, 129.9, 129.8, 129.3, 129.1, 129.0, 127.7, 127.5, 127.3, 124.2, 111.4, 110.1, 81.8, 80.5, 55.7, 55.4, 40.2, 39.6, 35.9, 19.8, 19.7.

[0043] 3) The high resolution mass spectrum of this compound is characterized as:

[0044] calcd for C 38 H 40 N2O4Na + , ([M+Na] + ) 611.2886, found 611.2883.

[0045] The physicochemical properties of compound I-4 are as follows:

[0046] 1) White solid, melting point 76.7-77.6 °C;

[0047] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0048] In deuterated chloroform as solvent, TMS as internal standard, the attribution of each peak is as follows: 1H NMR (400 MHz, CDC13): δ = 7.60 (s, 1H, Ar-H), 7.58 (s, 2H, Ar-H), 7.56 (s, 1H, Ar-H), 7.38-7.41 (m, 2H, Ar-H), 7.24 (s, 2H, Ar-H), 7.23 (s, 2H, Ar-H), 7.19 (d, J = 8.0 Hz, 2H, Ar-H), 6.92 (s, 1H Ar-H), 6.90 (s, 1H Ar-H), 5.04-5.12 (m, 1H, -CH2-C H -CH2-), 4.93-5.01 (m, 1H, -CH2-C H -CH2-), 3.86 (s, 3H, -OC H 3), 3.79 (s, 3H, -OC H 3), 3.24-3.36 (m, 2H), 3.03-3.21 (m, 4H), 2.83-2.93 (m, 4H), 1.25 (d, J = 7.2 Hz, 12H, 4x-CH-C H 3). 13 C NMR (100 MHz, CDC13): δ = 157.1, 156.8, 156.7, 155.6, 151.4, 151.3, 132.8, 131.9, 130.9, 130.6, 129.6, 129.4, 129.3, 127.9, 127.6, 127.0, 125.2, 111.7, 110.4, 82.2, 80.8, 56.0, 55.7, 40.5, 39.9, 36.2, 34.4, 24.1.

[0049] 3) The high resolution mass spectrum of this compound is characterized:

[0050] Using electrospray ionization: calcd for C 40 H 45 N2O4 + , ([M+H] + ) 617.3379, found 617.3384.

[0051] The physicochemical properties of compound I-5 are as follows:

[0052] 1) White solid, melting point 83.4-84.2°C;

[0053] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0054] In deuterated chloroform as solvent, TMS as internal standard, the peaks are assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.61 (s, 1H, Ar-H), 7.59 (s, 2H, Ar-H), 7.57 (s, 1H, Ar-H), 7.41 (s, 3H, Ar-H), 7.39 (s, 3H, Ar-H), 7.19 (d, J = 8.0 Hz, 2H, Ar-H), 6.93 (d, J = 2.0 Hz, 1H, Ar-H), 6.91 (d, J = 2.4 Hz, 1H, Ar-H), 5.04 - 5.12 (m, 1H, -CH2-C H -CH2-), 4.93 - 5.01 (m, 1H, -CH2-C H -CH2-), 3.86 (s, 3H, -OC H 3), 3.79 (s, 3H, -OC H 3), 3.25 - 3.37 (m, 2H), 3.03 - 3.23 (m, 4H), 2.84 - 2.93 (m, 2H), 1.32 (s, 18H, 6 x -C-C H 3). 13 C NMR (100 MHz, CDC13): δ = 157.1, 156.7, 156.6, 155.6, 153.7, 153.6, 132.8, 131.9, 130.9, 130.6, 129.6, 129.4, 129.3, 127.5, 127.2, 126.8, 125.9, 125.8, 125.2, 111.7, 110.4, 82.2, 80.9, 56.0, 55.7, 40.5, 39.8, 36.2, 35.2, 31.5.

[0055] 3) The high resolution mass spectrum of this compound is characterized as:

[0056] calcd for C 42 H 49 N2O4 + , ([M+H] + ) 645.3692, found 645.3689.

[0057] The physicochemical properties of compound I-6 are as follows:

[0058] 1) Light yellow solid, melting point 86.4 - 87.1 °C;

[0059] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0060] In deuterated chloroform as solvent, TMS as internal standard, the attribution of each peak is as follows: 1H NMR (400 MHz, CDC13): δ = 7.94-7.98 (m, 2H, Ar-H), 7.86 (d, J = 8.0 Hz, 2H, Ar-H), 7.81 (d, J = 7.6 Hz, 6H, Ar-H), 7.46-7.50 (m, 4H, Ar-H), 7.42 (s, 2H, Ar-H), 7.22 (d, J = 8.4 Hz, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 5.12-5.20 (m, 1H, -CH2-C H -CH2-), 5.00-5.08 (m, 1H, -CH2-C H -CH2-), 3.87 (s, 3H, -OC H 3), 3.79 (s, 3H, -OC H 3), 3.36-3.47 (m, 2H), 3.14-3.28 (m, 4H), 2.89-2.98 (m, 2H). 13 CNMR (100 MHz, CDC13): δ = 157.1, 157.0, 156.9, 155.7, 134.3, 134.2, 133.3, 133.2, 132.8, 131.9, 130.9, 130.6, 129.5, 129.4, 129.3, 128.8, 128.7, 128.6, 128.5, 128.1, 127.9, 127.7, 127.3, 127.2, 127.1, 127.0, 126.9, 125.1, 123.9, 123.8, 111.8, 110.4, 82.5, 81.2, 56.0, 55.7, 40.6, 39.7, 36.2.

[0061] 3) The high resolution mass spectrum of this compound is characterized as:

[0062] Using electrospray ionization: calcd for C 42 H 36 N2O4Na + , ([M + Na] + ) 655.2573, found 655.2562.

[0063] The physicochemical properties of compound I-7 are as follows:

[0064] 1) White solid, melting point 85.8-86.3°C;

[0065] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0066] Using deuterated chloroform as the solvent and TMS as the internal standard, the peaks are assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.89-7.93 (m, 2H, Ar-H), 7.87 (d, J = 5.2 Hz, 2H, Ar-H), 7.66 (d, J = 7.6 Hz, 2H, Ar-H), 7.48-7.52 (m, 2H, Ar-H), 7.42 (d, J = 8.4 Hz, 1H, Ar-H), 7.38 (s, 1H, Ar-H), 7.20 (d, J = 8.8 Hz, 2H, Ar-H), 6.94 (d, J = 2.4 Hz, 1H, Ar-H), 6.92 (d, J = 2.0 Hz, 1H, Ar-H), 5.12-5.20 (m, 1H, -CH2-C H -CH2-), 5.02-5.10 (m, 1H, -CH2-C H -CH2-), 3.88 (s, 3H, -OC H 3), 3.80 (s, 3H, -OC H 3), 3.26-3.37 (m, 2H), 3.04-3.23 (m, 4H), 2.90-2.98 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 157.1, 155.7, 155.2, 155.1, 133.4, 133.3, 132.8, 131.9, 131.7, 131.5, 130.9, 130.8, 130.5, 130.3, 129.9, 129.6, 129.4, 129.0, 124.7, 118.5, 118.4, 113.4, 113.3, 111.8, 110.5, 83.1, 81.9, 56.0, 55.8, 40.4, 39.1, 36.1.

[0067] 3) The high resolution mass spectrum of this compound is characterized as follows:

[0068] Using electrospray ionization: calcd for C 36 H 31 N4O4 + , ([M+H] + ) 583.2345, found 583.2350.

[0069] The physicochemical properties of compound I-8 are as follows:

[0070] 1) White solid, melting point 84.1-84.9 °C;

[0071] 2) The nuclear magnetic resonance spectrum of this compound is characterized as follows:

[0072] In deuterated chloroform as solvent, TMS as internal standard, the peaks are as follows: 1H NMR (400 MHz, CDC13): δ = 7.70 (d, J = 2.0 Hz, 1H, Ar-H), 7.67-7.68 (m, 1H, Ar-H), 7.49-7.52 (m, 1H, Ar-H), 7.45-7.47 (m, 2H, Ar-H), 7.39-7.43 (m, 2H, Ar-H), 7.36-7.37 (m, 1H, Ar-H), 7.19 (d, J = 7.2 Hz, 2H, Ar-H), 6.93 (d, J = 2.0 Hz, 1H, Ar-H), 6.91 (d, J = 2.4 Hz, 1H, Ar-H), 5.09-5.17 (m, 1H, -CH2-C H -CH2-), 4.99-5.07 (m, 1H, -CH2-C H -CH2-), 3.87 (s, 3H, -OC H 3), 3.80 (s, 3H, -OC H 3), 3.23-3.33 (m, 2H), 3.11-3.21 (m, 2H), 2.99-3.09 (m, 2H), 2.87-2.96 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 157.1, 155.7, 155.1, 155.0, 134.3, 134.2, 133.3, 133.2, 132.8, 131.9, 131.0, 130.9, 130.5, 130.3, 130.1, 129.5, 129.4, 129.1, 128.7, 126.0, 124.8, 111.7, 110.4, 82.9, 81.7, 56.0, 55.8, 40.4, 39.3, 36.1, 27.2.

[0073] 3) The high resolution mass spectrum of this compound is characterized as follows:

[0074] Using electrospray ionization: calcd for C 34 H 28 N2O4Na 35 Cl4 + , ([M+Na] + ) 691.0701, found 691.0693.

[0075] The physicochemical properties of compound I-9 are as follows:

[0076] 1) White solid, melting point 73.6-74.2 °C;

[0077] 2) The nuclear magnetic resonance spectrum of this compound is characterized as follows:

[0078] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ = 7.31-7.42 (m, 8H, Ar-H), 7.19 (d, J = 6.8Hz, 2H, Ar-H), 7.05-7.10 (m, 2H,Ar-H),6.93(d,J=1.6Hz,1H,Ar-H),6.91(d,J=2.4Hz,1H,Ar-H),5.08–5.16(m,1H,-CH2-C H -CH2-),4.98–5.05(m,1H,-CH2-C H -CH2-),3.87(s,3H,-OC H 3),3.79(s,3H,-OC H 3),3.23–3.35(m,2H),3.13–3.22(m,2H),3.02–3.11(m,2H),2.87–2.96(m,2H). 13 C NMR (100MHz, CDCl3): δ = 164.0 (d, J CF =245Hz),156.8,155.7(d,J CCCCF =3Hz),155.6(d,J CCCCF =3Hz),155.4,132.5,132.2(d,J CCCF =8Hz),131.9(d,J CCCF =8Hz),131.6,130.6,130.3,130.2,130.1,130.0,129.2,129.0,124.6,122.4,122.3,117.0(d,J CCF =21Hz),116.9(d,J CCF =21Hz),113.5(d,J CCF =23Hz),111.4,110.1,82.4,81.1,55.7,55.4,40.2,39.2,35.8,29.7.

[0079] 3) High-resolution mass spectrometric characteristics of the compound:

[0080] Using electrospray ionization: calcd for C 34 H 31 N2O4F2 + ,([M+H] + )569.2252,found 569.2258.

[0081] The physicochemical properties of compound I-10 are as follows:

[0082] 1) White solid, melting point 81.2-81.6 °C;

[0083] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0084] In deuterated chloroform as solvent, TMS as internal standard, wherein the peak assignment is: 1 H NMR (600 MHz, CDC13): δ = 7.59 (s, 1H, Ar-H), 7.57 (s, 2H, Ar-H), 7.56 (s, 1H, Ar-H), 7.40-7.42 (m, 1H, Ar-H), 7.37-7.38 (m, 1H, Ar-H), 7.35 (d, J = 2.4 Hz, 2H, Ar-H), 7.34 (d, J = 2.4 Hz, 2H, Ar-H), 7.19 (d, J = 8.4 Hz, 2H, Ar-H), 6.93 (d, J = 3.6 Hz, 1H, Ar-H), 6.91 (d, J = 2.8 Hz, 1H, Ar-H), 5.08-5.14 (m, 1H, -CH2-C H -CH2-), 4.98-5.03 (m, 1H, -CH2-C H -CH2-), 3.86 (s, 3H, -OC H 3), 3.79 (s, 3H, -OC H 3), 3.24-3.34 (m, 2H), 3.11-3.21 (m, 2H), 3.02-3.10 (m, 2H), 2.87-2.95 (m, 2H). 13 C NMR (150 MHz, CDC13): δ = 157.1, 156.0, 155.9, 155.7, 136.2, 136.1, 132.8, 131.9, 131.8, 130.9, 130.5, 129.5, 129.3, 129.2, 128.8, 128.5, 128.2, 111.7, 110.4, 82.6, 81.3, 56.0, 55.7, 40.5 39.6, 36.2.

[0085] 3) The high resolution mass spectrum characteristics of the compound:

[0086] Using electrospray ionization: calcd for C 34 H 30 N2O4 35 Cl2Na + , ([M+Na] + ) 623.1480, found 623.1478.

[0087] The physical and chemical properties of compound I-11 are as follows:

[0088] 1) white solid, melting point 86.4-87.1℃;

[0089] 2) the nuclear magnetic resonance spectrum characteristics of the compound are as follows:

[0090] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.51 (s, 4H, Ar-H), 7.50 (s, 4H, Ar-H), 7.39-7.42 (m, 1H, Ar-H), 7.36-7.37 (m, 1H, Ar-H), 7.19 (d, J = 7.2 Hz, 2H, Ar-H), 6.93 (d, J = 1.6 Hz, 1H, Ar-H), 6.91 (d, J = 2.0 Hz, 1H, Ar-H), 5.07-5.15 (m, 1H, -CH2-C H -CH2-), 4.96-5.04 (m, 1H, -CH2-C H -CH2-), 3.86 (s, 3H, -OC H 3), 3.79 (s, 3H, -OC H 3), 3.23-3.35 (m, 2H), 3.01-3.22 (m, 4H), 2.86-2.96 (m, 2H). 13 C NMR (100 MHz, CDCl3): δ = 156.8, 155.7, 155.6, 155.3, 132.4, 131.9, 131.8, 131.6, 130.6, 130.2, 129.2, 129.0, 128.9, 128.7, 128.1, 124.6, 124.2, 124.1, 111.4, 110.1, 99.3, 82.3, 81.0, 55.7, 55.4, 40.2, 39.2, 35.8, 29.7.

[0091] 3) the high resolution mass spectrum characteristics of the compound are as follows:

[0092] Using electrospray ionization: calcd for C 34 H 31 N2O4 79 Br2 + ,([M+H] + ) 689.0651, found 689.0657.

[0093] The physical and chemical properties of compound II-1 are as follows:

[0094] 1) white solid, melting point 74.4-75.2℃;

[0095] 2) The nuclear magnetic resonance spectrum of the compound is characterized by:

[0096] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned to: 1 H NMR (400 MHz, CDC13): δ = 7.63-7.65 (m, 4H, Ar-H), 7.36-7.38 (m, 6H, Ar-H), 7.23 (d, J = 2.0 Hz, 1H, Ar-H), 7.21 (d, J = 2.0 Hz, 1H, Ar-H), 7.12 (s, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.94-5.02 (m, 2H, 2 x -CH2-C H -CH2-), 3.74 (s, 6H, 2 x -OC H 3), 3.34 (dd, J = 10.0, 16.4 Hz, 2H), 3.05-3.15 (m, 4H), 2.83-2.88 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 156.4, 155.8, 132.4, 129.9, 129.7, 129.5, 128.6, 128.5, 127.6, 127.6, 126.6, 111.3, 82.0, 55.8, 40.1, 39.3.

[0097] 3) The high resolution mass spectrum of the compound is characterized by:

[0098] Using electrospray ionization: calcd for C 34 H 33 N2O4 + , ([M+H] + ) 533.2440, found 533.2441.

[0099] Figure 1 and Figure 2 are the nuclear magnetic resonance hydrogen spectrum and carbon spectrum of compound II-1, respectively.

[0100] The physical and chemical properties of compound II-2 are as follows:

[0101] 1) White solid, melting point 86.5-86.9°C;

[0102] 2) The nuclear magnetic resonance spectrum of the compound is characterized by:

[0103] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned to: 1H NMR (400 MHz, CDC13): δ = 7.54 (s, 2H, Ar-H), 7.52 (s, 2H, Ar-H), 7.23 (d, J = 2.4 Hz, 1H, Ar-H), 7.21 (d, J = 2.4 Hz, 1H, Ar-H), 7.19 (s, 2H, Ar-H), 7.17 (s, 2H, Ar-H), 7.11 (t, J = 1.6 Hz, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.92 - 5.00 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.35 (dd, J = 10.0, 16.4 Hz, 2H), 3.04 - 3.15 (m, 4H), 2.81 - 2.87 (m, 2H), 2.36 (s, 6H, 2 x -C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.8, 156.2, 140.5, 132.7, 129.8, 129.7, 128.9, 127.9, 127.3, 126.9, 111.7, 82.2, 56.1, 40.5, 39.8, 21.7.

[0104] 3) The high resolution mass spectrum of this compound is characterized:

[0105] Using electrospray ionization: calcd for C 36 H 36 N2O4Na + , ([M+Na] + ) 583.2573, found 583.2570.

[0106] The physicochemical properties of compound II-3 are as follows:

[0107] 1) White solid, melting point 80.2 - 80.6 °C;

[0108] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0109] In deuterated chloroform as solvent, TMS as internal standard, the assignment of each peak is as follows: 1H NMR (400 MHz, CDC13): δ = 7.45 (s, 2H, Ar-H), 7.36 (s, 1H, Ar-H), 7.34 (s, 1H, Ar-H), 7.22 (d, J = 1.2 Hz, 1H, Ar-H), 7.20 (d, J = 1.2 Hz, 1H, Ar-H), 7.14 (s, 1H, Ar-H), 7.12 (s, 3H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.91 - 4.99 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.34 (dd, J = 10.0, 16.4 Hz, 2H), 3.03 - 3.15 (m, 4H), 2.81 - 2.86 (m, 2H), 2.26 (s, 12H, 4 x -C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.5, 155.9, 138.9, 136.9, 132.5, 129.9, 129.5, 128.7, 127.7, 127.6, 127.3, 124.2, 111.4, 81.9, 55.8, 40.2, 39.6, 19.7, 19.6.

[0110] 3) The high resolution mass spectrum of this compound is characterized:

[0111] Using electrospray ionization: calcd for C 38 H 40 N2O4Na + , ([M+Na] + ) 611.2886, found 611.2883.

[0112] The physicochemical properties of compound II-4 are as follows:

[0113] 1) White solid, melting point 72.0 - 72.6 °C;

[0114] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0115] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.59 (s, 2H, Ar-H), 7.57 (s, 2H, Ar-H), 7.25 (s, 2H, Ar-H), 7.23 (s, 2H, Ar-H), 7.20 (s, 2H, Ar-H), 7.13 (s, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.93 - 5.01 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.36 (dd, J = 10.4, 16.8 Hz, 2H), 3.05 - 3.15 (m, 4H), 2.81 - 2.95 (m, 4H), 1.25 (d, J = 10.8 Hz, 12H, 4 x -CH-C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.7, 156.2, 151.4, 132.8, 129.8, 129.0, 127.9, 127.7, 127.1, 127.0, 111.7, 82.2, 56.1, 40.5, 39.8, 34.4, 24.1.

[0116] 3) The high resolution mass spectrum of this compound is characterized:

[0117] Using electrospray ionization: calcd for C 40 H 45 N2O4 + , ([M+H] + ) 617.3379, found 617.3384.

[0118] The physicochemical properties of compound II-5 are as follows:

[0119] 1) White solid, melting point 78.3 - 78.7 °C;

[0120] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0121] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned: 1H NMR (400 MHz, CDC13): δ = 7.60 (s, 2H, Ar-H), 7.58 (s, 2H, Ar-H), 7.41 (s, 2H, Ar-H), 7.40 (s, 2H, Ar-H), 7.23 (d, J = 2.0 Hz, 1H, Ar-H), 7.20 (d, J = 2.0 Hz, 1H, Ar-H), 7.13 (s, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.93 - 5.01 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.37 (dd, J = 10.4, 16.8 Hz, 2H), 3.05 - 3.15 (m, 4H), 2.81 - 2.87 (m, 2H), 1.32 (s, 18H, 6 x -C-C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.6, 156.2, 153.7, 132.8, 129.8, 129.0, 128.0, 127.3, 126.8, 126.0, 111.7, 82.2, 56.1, 40.5, 39.8, 35.2, 31.5.

[0122] 3) The high resolution mass spectrum of this compound is characterized:

[0123] Using electrospray ionization: calcd for C 42 H 49 N2O4 + , ([M+H] + ) 645.3692, found 645.3694.

[0124] The physicochemical properties of compound II-6 are as follows:

[0125] 1) Light yellow solid, melting point 83.6-84.3°C;

[0126] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0127] In deuterated chloroform as solvent, TMS as internal standard, the assignment of each peak is as follows: 1H NMR (400 MHz, CDC13): δ = 7.96 (s, 1H, Ar-H), 7.94 (s, 1H, Ar-H), 7.84 (s, 2H, Ar-H), 7.81 (s, 3H, Ar-H), 7.79 (s, 3H, Ar-H), 7.45-7.50 (m, 4H, Ar-H), 7.23-7.24 (m, 2H, Ar-H), 7.15 (d, J = 1.6 Hz, 2H, Ar-H), 6.94 (s, 1H Ar-H), 6.92 (s, 1H Ar-H), 5.00-5.07 (m, 2H, 2x-CH2-C H -CH2-), 3.75 (s, 6H, 2x-OC H 3), 3.47 (dd, J = 10.0, 16.4 Hz, 2H), 3.12-3.22 (m, 4H), 2.86-2.91 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 156.9, 156.2, 134.3, 133.3, 132.8, 129.9, 128.9, 128.8, 128.6, 128.0, 127.7, 127.3, 127.1, 127.0, 123.9, 111.7, 82.5, 56.1, 40.5, 39.7.

[0128] 3) The high resolution mass spectrum characteristics of the compound:

[0129] Using electrospray ionization: calcd for C 42 H 36 N2O4Na + , ([M+H] + ) 655.2573, found 655.2568.

[0130] The physicochemical properties of compound II-7 are as follows:

[0131] 1) White solid, melting point 84.1-84.8 °C;

[0132] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0133] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.92 (s, 1H, Ar-H), 7.90 (s, 1H, Ar-H), 7.86 (s, 2H, Ar-H), 7.66 (s, 1H, Ar-H), 7.65 (s, 1H, Ar-H), 7.50 (t, J = 7.6 Hz, 2H, Ar-H), 7.23 (d, J = 1.6 Hz, 1H, Ar-H), 7.21 (d, J = 1.6 Hz, 1H, Ar-H), 7.12 (s, 2H, Ar-H), 6.94 (s, 1H Ar-H), 6.92 (s, 1H Ar-H), 5.02 - 5.10 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.78 (dd, J = 10.4, 16.4 Hz, 2H), 3.06 - 3.14 (m, 4H), 2.93 (dd, J = 6.8, 14.0 Hz, 2H). 13 CNMR (100 MHz, CDC13): δ = 156.3, 155.1, 133.3, 132.8, 132.7, 131.6, 130.8, 130.3, 129.9, 129.8, 128.4, 128.0, 118.4, 113.4, 111.7, 83.1, 83.0, 56.1, 40.4, 39.1.

[0134] 3) The high resolution mass spectrum of this compound is characterized as:

[0135] Using electrospray ionization: calcd for C 34 H 31 N2O4 79 Br2 + ,([M+H] + )583.2345, found 583.2347.

[0136] The physical and chemical properties of compound II-8 are as follows:

[0137] 1) White solid, melting point 82.4-82.8°C;

[0138] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0139] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as: 1H NMR (400 MHz, CDC13): δ = 7.68 (d, J = 1.2 Hz, 2H, Ar-H), 7.50 (d, J = 1.6 Hz, 1H, Ar-H), 7.48 (d, J = 1.6 Hz, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 7.43 (s, 1H, Ar-H), 7.22 (d, J = 2.0 Hz, 1H, Ar-H), 7.20 (d, J = 2.0 Hz, 1H, Ar-H), 7.11 (s, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.99 - 5.06 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.33 (dd, J = 10.4, 16.4 Hz, 2H), 3.08 - 3.13 (m, 2H), 3.01 - 3.07 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 156.0, 154.7, 133.9, 133.0, 132.4, 130.7, 129.8, 129.6, 129.5, 128.3, 128.2, 127.6, 125.6, 111.4, 82.6, 55.8, 40.1, 39.0, 29.7.

[0140] 3) The high resolution mass spectrum of this compound is characterized:

[0141] Using electrospray ionization: calcd for C 34 H 29 N2O4 35 Cl4 + , ([M+H] + ) 669.0881, found 669.0881.

[0142] The physicochemical properties of compound II-9 are as follows:

[0143] 1) White solid, melting point 73.4-74.2 °C;

[0144] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0145] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned: 1H NMR (400 MHz, CDC13): δ = 7.31 - 5.40 (m, 6H, Ar-H), 7.23 (d, J = 2.4 Hz, 1H, Ar-H), 7.21 (d, J = 2.0 Hz, 1H, Ar-H), 7.11 - 7.12 (m, 2H, Ar-H), 7.05 - 7.10 (m, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.97 - 5.05 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OCH3), 3.35 (dd, J = 10.0, 16.4 Hz, 2H), 3.03 - 3.14 (m, 4H), 2.85 - 2.90 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 164.0 (d, J CF = 245 Hz), 155.9, 155.6 (d, J CCCCF = 3 Hz), 132.4, 132.0 (d, J CCCF = 8 Hz), 130.3 (d, J CCCF = 8 Hz), 129.5, 128.3, 127.6, 122.4 (d, J CCCCF = 3 Hz), 117.0 (d, J CCF = 21 Hz), 113.5 (d, J CCF = 23 Hz), 111.4, 82.4, 55.8, 40.1, 39.2, 29.7.

[0146] 3) The high resolution mass spectrum of this compound is characterized as:

[0147] Using electrospray ionization: calcd for C 34 H 31 N2O4F2 + , ([M+H] + ) 569.2252, found 569.2258.

[0148] The physical and chemical properties of compound II-10 are as follows:

[0149] 1) White solid, melting point 75.5 - 76.1 °C;

[0150] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0151] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1H NMR (600 MHz, CDC13): δ = 7.58 (s, 2H, Ar-H), 7.56 (s, 2H, Ar-H), 7.36 (s, 2H, Ar-H), 7.34 (s, 2H, Ar-H), 7.22 (d, J = 2.4 Hz, 1H, Ar-H), 7.21 (d, J = 2.4 Hz, 1H, Ar-H), 7.11 (s, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.97 - 5.03 (m, 2H, 2 x -CH2-C H -CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.29 - 3.34 (m, 2H), 3.10 - 3.13 (m, 2H), 3.04 - 3.08 (m, 2H), 2.85 - 2.88 (m, 2H). 13 C NMR (150 MHz, CDC13): δ = 156.2, 155.9, 136.2, 132.7, 129.9, 129.3, 128.7, 128.6, 128.2, 127.9, 111.7, 82.7, 56.1, 40.5, 39.6.

[0152] 3) The high resolution mass spectrum of this compound is characterized:

[0153] Using electrospray ionization: calcd for C 34 H 30 N2O4 35 Cl2Na + , ([M+Na] + ) 623.1480, found 623.1481.

[0154] The physicochemical properties of compound II-11 are as follows:

[0155] 1) White solid, melting point 83.4 - 84.1 °C;

[0156] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0157] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.50 (s, 8H, Ar-H), 7.22 (d, J = 2.0 Hz, 1H, Ar-H), 7.20 (d, J = 2.0 Hz, 1H, Ar-H), 7.11 (d, J = 2.0 Hz, 2H, Ar-H), 6.93 (s, 1H Ar-H), 6.91 (s, 1H Ar-H), 4.96 - 5.04 (m, 2H, 2 x -CH2-C H-CH2-), 3.75 (s, 6H, 2 x -OC H 3), 3.28 - 3.39 (m, 2H), 3.03 - 3.14 (m, 4H), 2.89 (dd, J = 6.8, 14.0 Hz, 2H). 13 C NMR (100 MHz, CDC13): δ = 155.9, 155.7, 154.3, 138.4, 132.4, 131.9, 131.7, 129.5, 128.7, 128.4, 128.1, 127.6, 124.2, 121.3, 115.2, 111.3, 82.4, 55.8, 41.6, 40.2, 39.2, 29.7, 13.9.

[0158] 3) The high resolution mass spectrum of this compound is characterized as:

[0159] Using electrospray ionization: calcd for C 34 H 31 N2O4 79 Br2 + , ([M+H] + ) 689.0651, found 689.0660.

[0160] The physical and chemical properties of compound III-1 are as follows:

[0161] 1) White solid, melting point 78.7-79.5°C;

[0162] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0163] Using deuterated chloroform as solvent and TMS as internal standard, the attribution of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.59 - 7.64 (m, 4H, Ar-H), 7.35 - 7.38 (m, 6H, Ar-H), 7.22 (s, 1H, Ar-H), 7.20 (dd, J = 2.4, 8.4 Hz, 1H, Ar-H), 7.10 (d, J = 6.8 Hz, 2H, Ar-H), 7.05 (s, 1H, -O H ), 6.97 (d, J = 8.0 Hz, 1H, Ar-H), 6.92 (d, J = 8.8 Hz, 1H, Ar-H), 5.46 (s, 1H, -O H ), 5.07 - 5.15 (m, 1H, -CH2-C H -CH2-), 4.93 - 5.01 (m, 1H, -CH2-C H-CH2-),3.31–3.45(m,2H),3.01–3.21(m,5H),2.88(dd,J=6.8,14.4Hz,1H). 13 C NMR (100MHz, CDCl3): δ=158.2,157.1,155.1,151.8,132.7,131.4,130.7,130.5,129.8,129.7,129.6,129.4,1 29.3,129.2,129.0,128.2,129.1,127.0,124.3,117.7,116.3,82.4,81.9,40.5,39.8,39.7,36.5,27.2,23.0.

[0164] 3) High-resolution mass spectrometric characteristics of the compound:

[0165] Using electrospray ionization: calcd for C 32 H 28 N2O4Na + ,([M+Na] + )527.1947,found 527.1949.

[0166] The physicochemical properties of compound III-2 are as follows:

[0167] 1) White solid, melting point 83.0–83.6°C;

[0168] 2) NMR spectrum characteristics of the compound:

[0169] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ=7.49–7.54(m,4H,Ar-H),7.21(s,2H,Ar-H),7.16–7.19(m,4H,Ar-H),7.10(d, J=8.8Hz,2H,Ar-H),6.99(d,J=7.6Hz,1H,Ar-H),6.92(d,J=8.0Hz,1H,Ar-H),5.06–5.13(m,1H,-CH2-C H -CH2-),4.91–4.99(m,1H,-CH2-C H -CH2-),3.30–3.45(m,2H),3.02–3.19(m,5H),2.87(dd,J=6.8,14.0Hz,1H),2.36(s,3H,-C H 3),2.35(s,3H,-C H 3). 13C NMR (100 MHz, CDC13): δ = 158.3, 157.0, 155.2, 151.8, 141.0, 140.7, 132.7, 131.3, 129.7, 129.6, 129.3, 129.2, 128.2, 127.1, 126.9, 126.4, 124.4, 117.9, 116.3, 82.2, 81.8, 40.5, 39.9, 39.8, 36.6, 27.2, 21.8.

[0170] 3) The high resolution mass spectrum of this compound is characterized by:

[0171] Using electrospray ionization: calcd for C 34 H 32 N2O4Na + , ([M + Na] + ) 555.2260, found 555.2267.

[0172] The physicochemical properties of compound III-3 are as follows:

[0173] 1) Light yellow solid, melting point 86.9-87.5 °C;

[0174] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0175] In deuterated chloroform as solvent, TMS as internal standard, the assignment of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.43 (s, 1H, Ar-H), 7.41 (s, 1H, Ar-H), 7.30-7.35 (m, 3H, Ar-H), 7.22 (s, 1H, -OH), 7.20 (dd, J = 2.0, 8.4 Hz, 1H, Ar-H), 7.14 (d, J = 7.6 Hz, 2H, Ar-H), 7.08-7.10 (m, 2H, Ar-H), 6.98 (d, J = 8.4 Hz, 1H, Ar-H), 6.92 (d, J = 8.8 Hz, 1H, Ar-H), 5.59 (s, 1H, -OH), 5.05-5.12 (m, 1H, -CH2-C H -CH2-), 4.90-4.98 (m, 1H, -CH2-C H -CH2-), 3.30-3.42 (m, 2H), 3.02-3.18 (m, 5H), 2.85 (dd, J = 6.8, 14.0 Hz, 1H), 2.23-2.26 (m, 12H, 4x-CH3). 13C NMR (100 MHz, CDC13): δ = 158.4, 157.1, 155.2, 151.8, 139.8, 139.4, 137.4, 137.3, 132.7, 131.3, 130.2, 129.8, 129.6, 129.3, 128.2, 128.1, 128.0, 127.3, 126.7, 124.7, 124.5, 124.4, 118.0, 116.3, 82.1, 81.8, 40.5, 39.9, 39.8, 36.7, 31.9, 27.2, 20.2, 20.1, 20.0.

[0176] 3) The high resolution mass spectrum of this compound is characterized by:

[0177] Using electrospray ionization: calcd for C 36 H 36 N2O4Na + , ([M+Na] + ) 583.2573, found 583.2575.

[0178] The physical and chemical properties of compound III-4 are as follows:

[0179] 1) Yellow solid, melting point 89.5-90.3 °C;

[0180] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0181] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 7.53-7.58 (m, 4H, Ar-H), 7.21-7.24 (m, 6H, Ar-H), 7.18 (s, 1H, -O H ), 7.09 (d, J = 6.8 Hz, 2H, Ar-H), 6.98 (d, J = 8.0 Hz, 1H, Ar-H), 6.91 (d, J = 8.4 Hz, 1H, Ar-H), 5.54 (s, 1H, -O H ), 5.05-5.13 (m, 1H, -CH2-C H -CH2-), 4.91-4.99 (m, 1H, -CH2-C H -CH2-), 3.30-3.43 (m, 2H), 3.02-3.19 (m, 5H), 2.81-2.94 (m, 3H), 1.22-1.25 (m, 12H, 4x-CH-C H 3). 13C NMR (100 MHz, CDC13): δ = 158.2, 156.9, 155.2, 151.9, 151.8, 151.6, 132.7, 131.4, 129.8, 129.6, 129.4, 129.3, 128.3, 127.4, 127.2, 127.1, 127.0, 126.9, 124.5, 118.0, 116.3, 82.2, 81.9, 40.5, 40.0, 39.9, 36.6, 34.4, 30.0, 24.1, 24.0.

[0182] 3) The high resolution mass spectrum of this compound is characterized by:

[0183] Using electrospray ionization: calcd for C 38 H 40 N2O4Na + , ([M+Na] + ) 611.2886, found 611.2878.

[0184] The physicochemical properties of compound III-5 are as follows:

[0185] 1) Light yellow solid, melting point 98.6-99.4 °C;

[0186] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0187] Using deuterated chloroform as solvent and TMS as internal standard, the attribution of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.54-7.59 (m, 4H, Ar-H), 7.37-7.41 (m, 4H, Ar-H), 7.23 (s, 1H, -OH), 7.21 (s, 1H, Ar-H), 7.19 (s, 1H, Ar-H), 7.09 (d, J = 7.2 Hz, 2H, Ar-H), 6.98 (d, J = 8.0 Hz, 1H, Ar-H), 6.91 (d, J = 8.4 Hz, 1H, Ar-H), 5.52 (s, 1H, -OH), 5.06-5.13 (m, 1H, -CH2-C H -CH2-), 4.91-4.99 (m, 1H, -CH2-C H -CH2-), 3.31-3.44 (m, 2H), 3.03-3.20 (m, 5H), 2.81-2.86 (m, 1H), 1.31 (s, 9H, 3x-C-CH3), 1.30 (s, 9H, 3x-C-CH3). 13C NMR (100 MHz, CDC13): δ = 158.2, 156.9, 155.3, 154.2, 153.8, 151.9, 132.7, 131.4, 129.8, 129.6, 129.4, 129.3, 128.3, 127.0, 126.9, 126.8, 126.5, 126.0, 125.9, 124.5, 118.0, 116.3, 82.2, 81.9, 40.5, 39.9, 39.8, 36.6, 35.2, 31.5, 31.4.

[0188] 3) The high resolution mass spectrum of this compound is characterized by:

[0189] Using electrospray ionization: calcd for C 40 H 44 N2O4Na + , ([M + Na] + ) 639.3199, found 639.3191.

[0190] The physicochemical properties of compound III-6 are as follows:

[0191] 1) White solid, melting point 98.9-99.8 °C;

[0192] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0193] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 7.95 (d, J = 8.8 Hz, 1H, Ar-H), 7.89 (d, J = 8.4 Hz, 1H, Ar-H), 7.84 (s, 2H, Ar-H), 7.79-7.82 (m, 6H, Ar-H), 7.47-7.52 (m, 4H, Ar-H), 7.20-7.24 (m, 2H, Ar-H), 7.10-7.14 (m, 2H, Ar-H), 7.00 (d, J = 8.4 Hz, 1H, Ar-H), 6.94 (d, J = 8.4 Hz, 1H, Ar-H), 5.32 (s, 1H, -OH), 5.12-5.19 (m, 1H, -CH2-C H -CH2-), 4.98-5.05 (m, 1H, -CH2-C H -CH2-), 3.41-3.56 (m, 2H), 3.25-3.31 (m, 1H), 3.05-3.20 (m, 4H), 2.91 (dd, J = 6.8, 14.4 Hz, 1H). 13C NMR (100 MHz, CDC13): δ = 158.1, 156.8, 154.9, 151.5, 134.1, 134.0, 132.9, 132.8, 132.4, 131.0, 129.6, 129.3, 129.2, 129.0, 128.9, 128.6, 128.5, 128.4, 128.3, 127.9, 127.8, 127.2, 127.1, 127.0, 126.9, 126.7, 126.6, 124.1, 123.4, 117.7, 116.0, 82.2, 81.9, 40.2, 39.4, 39.3, 36.3, 30.9.

[0194] 3) The high resolution mass spectrum of this compound is characterized by:

[0195] Using electrospray ionization: calcd for C 40 H 32 N2O4Na + , ([M+Na] + ) 627.2260, found 627.2261.

[0196] The physicochemical properties of compound III-7 are as follows:

[0197] 1) Light yellow solid, melting point 102.4-102.8 °C;

[0198] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0199] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.85-7.87 (m, 3H, Ar-H), 7.81 (s, 1H, Ar-H), 7.62-7.65 (m, 2H, Ar-H), 7.51 (d, J = 7.6 Hz, 1H, Ar-H), 7.47 (d, J = 8.0 Hz, 1H, Ar-H), 7.19 (d, J = 8.4 Hz, 1H, Ar-H), 7.09 (d, J = 8.4 Hz, 2H, Ar-H), 6.88-6.93 (m, 3H, Ar-H), 5.72 (s, 1H, -OH), 5.14-5.21 (m, 1H, -CH2-C H -CH2-), 5.00-5.08 (m, 1H, -CH2-C H -CH2-), 3.32-3.41 (m, 2H), 3.16-3.22 (m, 1H), 3.03-3.09 (m, 4H), 2.92 (dd, J = 6.4, 14.0 Hz, 1H). 13C NMR (100 MHz, CDC13): δ = 156.3, 155.3, 154.7, 152.0, 133.6, 133.4, 132.7, 131.4, 131.3, 131.0, 130.9, 130.5, 130.4, 129.8, 129.6, 129.5, 128.9, 128.2, 123.9, 118.4, 118.3, 117.3, 116.4, 113.3, 83.1, 82.5, 40.4, 39.2, 39.1, 36.1, 31.3.

[0200] 3) The high resolution mass spectrum of this compound is characterized by:

[0201] Using electrospray ionization: calcd for C 34 H 26 N4O4Na + , ([M+Na] + ) 577.1852, found 577.1850.

[0202] The physicochemical properties of compound III-8 are as follows:

[0203] 1) Light yellow solid, melting point 96.6-97.4°C;

[0204] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0205] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.68 (s, 1H, Ar-H), 7.67 (s, 1H, Ar-H), 7.43-7.49 (m, 4H, Ar-H), 7.23 (d, J = 8.4 Hz, 2H, Ar-H), 7.11 (d, J = 9.6 Hz, 2H, Ar-H), 6.98 (d, J = 8.0 Hz, 1H, Ar-H), 6.92 (d, J = 8.0 Hz, 1H, Ar-H), 6.63 (s, 1H, -O H ), 5.28 (s, 1H, -O H ), 5.13-5.20 (m, 1H, -CH2-C H -CH2-), 4.98-5.06 (m, 1H, -CH2-C H -CH2-), 3.28-3.43 (m, 2H), 2.99-3.17 (m, 5H), 2.86-2.91 (m, 1H). 13C NMR (100 MHz, CDC13): δ = 156.0, 154.8, 154.6, 151.6, 134.4, 134.1, 133.1, 133.0, 132.4, 131.0, 130.8, 130.7, 129.6, 129.3, 129.1, 128.7, 128.5, 128.4, 127.8, 125.8, 125.7, 123.8, 117.5, 116.0, 82.6, 82.2, 40.1, 39.0, 38.9, 36.0.

[0206] 3) The high resolution mass spectrum of this compound is characterized by:

[0207] Using electrospray ionization: calcd for C 32 H 24 N2O4Na 35 Cl4 + ,([M+Na] + ) 663.0388, found 663.0382.

[0208] The physicochemical properties of compound III-9 are as follows:

[0209] 1) White solid, melting point 88.1-88.8 °C;

[0210] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0211] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.31-7.39 (m, 6H, Ar-H), 7.23 (s, 1H, Ar-H), 7.21 (dd, J = 2.0, 8.0 Hz, 1H, Ar-H), 7.05-7.10 (m, 4H, Ar-H), 6.97 (d, J = 8.4 Hz, 1H, Ar-H), 6.92 (d, J = 8.8 Hz, 1H, Ar-H), 6.83 (s, 1H, -O H ), 5.43 (s, 1H, -O H ), 5.10-5.17 (m, 1H, -CH2-C H -CH2-), 4.96-5.04 (m, 1H, -CH2-C H -CH2-), 3.30-3.43 (m, 2H), 3.01-3.19 (m, 5H), 2.90 (dd, J = 6.4, 14.0 Hz, 1H). 13C NMR (100 MHz, CDC13): δ = 164.2, 161.8, 161.7, 157.3, 157.2, 156.0, 154.9, 161.8, 132.6, 132.0, 131.9, 131.5, 131.4, 131.3, 130.7, 130.6, 130.5, 130.4, 129.8, 129.5, 129.4, 129.1, 128.1, 124.2, 122.8, 122.7, 122.6, 117.7, 117.6, 117.4, 117.3, 117.1, 116.3, 113.9, 113.8, 113.7, 113.6, 82.6, 82.2, 40.4, 39.5, 39.4, 36.4, 29.9.

[0212] 3) The high resolution mass spectrum of this compound is characterized by:

[0213] Using electrospray ionization: calcd for C 32 H 27 N2O4F2 + ,([M+Na] + ) 541.1939, found 541.1942.

[0214] The physicochemical properties of compound III-10 are as follows:

[0215] 1) White solid, melting point 73.6-74.2 °C;

[0216] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0217] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.51-7.56 (m, 4H, Ar-H), 7.32-7.35 (m, 4H, Ar-H), 7.22-7.23 (m, 1H, Ar-H), 7.17-7.20 (m, 1H, Ar-H), 7.08-7.10 (m, 2H, Ar-H), 6.96 (d, J = 8.0 Hz, 1H, Ar-H), 6.91 (d, J = 8.8 Hz, 1H, Ar-H), 6.84 (s, 1H, -OH), 5.42 (s, 1H, -OH), 5.08-5.16 (m, 1H, -CH2-C H -CH2-), 4.95-5.02 (m, 1H, -CH2-C H -CH2-), 3.29-3.42 (m, 2H), 3.01-3.18 (m, 5H), 2.90 (dd, J = 6.4, 14.4 Hz, 1H).13 C NMR (100MHz, CDCl3): δ=157.0,155.8,154.6,151.5,136.3,136.0,132.4,131.0,129.6,129.3,129.0,12 8.9,128.8,128.0,127.9,127.8,127.7,127.4,123.9,117.5,116.0,82.3,81.9,40.2,39.3,39.2,36.1.

[0218] 3) High-resolution mass spectrometric characteristics of the compound:

[0219] Using electrospray ionization: calcd for C 32 H 27 N2O4 35 Cl2 + ,([M+Na] + )573.1348,found573.1351.

[0220] The physicochemical properties of compound III-11 are as follows:

[0221] 1) White solid, melting point 94.4–94.9°C;

[0222] 2) NMR spectrum characteristics of the compound:

[0223] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ=7.44–7.51(m,8H,Ar-H),7.22(s,1H,Ar-H),7.16–7.19(m,1H,Ar-H),7.09(d,J=7.2Hz,2H,Ar-H ),6.95(d,J=8.4Hz,1H,Ar-H),6.91(d,J=8.8Hz,1H,Ar-H),6.83(s,1H,-OH),5.44(s,1H,-OH),5.08–5.15(m,1H,-CH2-C H -CH2-),4.94–5.02(m,1H,-CH2-C H -CH2-),3.29–3.41(m,2H),3.00–3.17(m,5H),2.89(dd,J=6.4,14.0Hz,1H). 13C NMR (100 MHz, CDC13): δ = 157.4, 156.3, 154.9, 151.8, 132.7, 132.3, 132.2, 131.4, 129.8, 129.6, 129.4, 129.1, 128.7, 128.5, 128.4, 128.2, 128.1, 125.0, 124.7, 124.2, 117.6, 116.3, 82.6, 82.2, 40.5, 39.6, 39.5, 36.4.

[0224] 3) The high resolution mass spectrum of this compound is characterized by:

[0225] Using electrospray ionization: calcd for C 32 H 26 N2O4 79 Br2Na + ,([M+Na] + ) 683.0157, found 683.0151.

[0226] The physicochemical properties of compound IV-1 are as follows:

[0227] 1) White solid, melting point 79.0-79.8 °C;

[0228] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0229] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.59-7.61 (m, 4H, Ar-H), 7.36 (d, J = 5.6 Hz, 6H, Ar-H), 7.15 (d, J = 8.0 Hz, 4H, Ar-H), 6.97 (s, 1H, Ar-H), 6.95 (s, 1H, Ar-H), 6.93 (s, 2H, 2 x -OH), 4.93-5.00 (m, 2H, 2 x -CH2-C H -CH2-), 3.38 (dd, J = 10.0 16.4 Hz, 2H), 3.02-3.10 (m, 4H), 2.91 (dd, J = 6.4, 14.4 Hz, 2H). 13 C NMR (100 MHz, CDC13): δ = 156.9, 151.9, 132.3, 130.4, 130.2, 129.5, 128.7, 126.7, 125.3, 125.2, 117.2, 81.9, 40.2, 39.5, 26.9, 22.6.

[0230] 3) The high resolution mass spectrum of this compound is characterized by:

[0231] calcd for C 32 H 28 N2O4Na + ,([M+Na] + )527.1947,found 527.1953.

[0232] The physicochemical properties of compound IV-2 are as follows:

[0233] 1) white solid, melting point 85.2-85.8℃;

[0234] 2) the nuclear magnetic resonance spectrum characteristics of the compound:

[0235] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1 H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 7.6 Hz, 6H, Ar-H), 7.15-7.17 (m, 6H, Ar-H), 7.13 (s, 1H, -OH), 7.11 (s, 1H, -OH), 6.98 (s, 1H, Ar-H), 6.96 (s, 1H, Ar-H), 4.90-4.98 (m, 2H, 2 × -CH2-C H -CH2-), 3.36 (dd, J = 10.4, 16.8 Hz, 2H), 3.01-3.08 (m, 4H), 2.88 (dd, J = 6.4, 14.0 Hz, 2H), 2.34 (s, 6H, 2 × -CH3). 13 CNMR (100 MHz, CDCl3): δ = 157.2, 152.2, 140.8, 132.6, 130.7, 129.9, 129.8, 126.9, 126.7, 125.7, 117.6, 82.1, 40.5, 40.0, 27.2, 21.8.

[0236] 3) the high resolution mass spectrum characteristics of the compound:

[0237] calcd for C 34 H 33 N2O4 + ,([M+Na] + )533.2440,found 533.2446.

[0238] The physicochemical properties of compound IV-3 are as follows:

[0239] 1) white solid, melting point 96.4-97.0℃;

[0240] 2) the nuclear magnetic resonance spectrum characteristics of the compound:

[0241] The peaks were assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.40 (s, 2H, Ar-H), 7.32 (s, 2H, Ar-H), 7.30 (s, 2H, Ar-H), 7.16 (s, 2H, 2 x -O H ), 7.14 (s, 1H, Ar-H), 7.11 (s, 2H, Ar-H), 7.09 (s, 1H, Ar-H), 6.97 (s, 1H, Ar-H), 6.95 (s, 1H, Ar-H), 4.89 - 4.97 (m, 2H, 2 x -CH2-C H -CH2-), 3.28 - 3.35 (m, 2H), 3.01 - 3.07 (m, 4H), 2.88 (dd, J = 6.0, 14.0 Hz, 2H), 2.24 (s, 6H, 2 x -C H 3), 2.23 (s, 6H, 2 x -C H 3). 13 C NMR (100 MHz, CDC13): δ = 157.3, 152.3, 139.5, 137.4, 132.6, 130.7, 130.3, 130.0, 129.9, 128.1, 127.1, 125.6, 124.6, 117.6, 82.0, 40.5, 40.4, 40.1, 40.0, 20.1, 20.0.

[0242] 3) The high resolution mass spectrum of this compound is characterized as:

[0243] Using electrospray ionization: calcd for C 36 H 36 N2O4Na + , ([M+Na] + ) 583.2573, found 583.2564.

[0244] The physicochemical properties of compound IV-4 are as follows:

[0245] 1) Light yellow solid, melting point 85.4 - 86.2 °C;

[0246] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0247] The peaks were assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.55 (s, 2H, Ar-H), 7.53 (s, 2H, Ar-H), 7.23 (s, 2H, Ar-H), 7.21 (s, 2H, Ar-H), 7.17 (s, 2H, 2 x -O H ), 7.15 (s, 2H, Ar-H), 7.13 (s, 2H, Ar-H), 6.98 (s, 1H, Ar-H), 6.96 (s, 1H, Ar-H), 4.91 - 4.99 (m, 2H, 2 x -CH2-C H -CH2-), 3.38 (dd, J = 10.4, 16.8 Hz, 2H), 3.02 - 3.09 (m, 4H), 2.84 - 2.93 (m, 4H), 1.24 (d, J = 6.8 Hz, 12H, 4 x -CH-C H 3). 13 C NMR (100 MHz, CDC13): δ = 157.1, 152.3, 151.7, 132.6, 130.8, 130.0, 129.9, 127.2, 127.1, 127.0, 125.5, 117.6, 82.1, 40.5, 40.0, 34.4, 24.1.

[0248] 3) The high resolution mass spectrum of this compound is characterized:

[0249] Using electrospray ionization: calcd for C 38 H 40 N2O4Na + , ([M + Na] + ) 611.2886, found 611.2878.

[0250] The physicochemical properties of compound IV-5 are as follows:

[0251] 1) Light yellow solid, melting point 89.8-90.6°C;

[0252] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0253] With deuterated chloroform as the solvent and TMS as the internal standard, the assignment of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.56 (s, 2H, Ar-H), 7.54 (s, 2H, Ar-H), 7.39 (s, 2H, Ar-H), 7.37 (s, 2H, Ar-H), 7.17 (s, 2H, 2 x -O H), 7.13 (s, 2H, Ar-H), 6.98 (s, 1H, Ar-H), 6.96 (s, 1H, Ar-H), 4.92-4.99 (m, 2H, 2 x -CH2-C H -CH2-), 3.38 (dd, J = 10.4, 16.8 Hz, 2H), 3.02-3.10 (m, 4H), 2.89 (dd, J = 6.0, 14.0 Hz, 2H), 1.30 (s, 18H, 6 x -C-C H 3). 13 C NMR (100 MHz, CDC13): δ = 157.1, 153.9, 152.3, 132.6, 130.8, 130.0, 129.9, 126.8, 126.0, 125.5, 117.6, 82.1, 40.5, 40.0, 35.2, 31.5.

[0254] 3) The high resolution mass spectrum of this compound is characterized:

[0255] calcd for C 40 H 44 N2O4Na + , ([M+Na] + ) 639.3199, found 639.3196.

[0256] The physicochemical properties of compound IV-6 are as follows:

[0257] 1) White solid, melting point 95.9-96.6 °C;

[0258] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0259] In deuterated chloroform as solvent, TMS as internal standard, the assignment of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.89-7.90 (m, 1H, Ar-H), 7.87-7.88 (m, 1H, Ar-H), 7.81 (s, 2H, 2 x -OH), 7.76-7.79 (m, 6H, Ar-H), 7.43-7.49 (m, 4H, Ar-H), 7.18 (d, J = 2.4 Hz, 3H, Ar-H), 7.16 (d, J = 2.0 Hz, 1H, Ar-H), 6.99 (s, 1H, Ar-H), 6.97 (s, 1H, Ar-H), 4.96-5.04 (m, 2H, 2 x -CH2-C HH NMR (400 MHz, CDC13): δ = 7.87 (s, 1 H, Ar-H), 7.85 (s, 1 H, Ar-H), 7.82 (s, 2H, Ar-H), 7.64 (s, 1 H, Ar-H), 7.62 (s, 1 H, Ar-H), 7.45 - 7.49 (m, 2H, Ar-H), 7.14 - 7.17 (m, 4H, Ar-H), 6.97 (s, 2H, 2x-OH), 6.95 (s, 1 H, Ar-H), 6.93 (s, 1 H, Ar-H), 5.00 - 5.08 (m, 2H, 2x-CH2-C 13 H NMR (400 MHz, CDC13): δ = 7.87 (s, 1 H, Ar-H), 7.85 (s, 1 H, Ar-H), 7.82 (s, 2H, Ar-H), 7.64 (s, 1 H, Ar-H), 7.62 (s, 1 H, Ar-H), 7.45 - 7.49 (m, 2H, Ar-H), 7.14 - 7.17 (m, 4H, Ar-H), 6.97 (s, 2H, 2x-OH), 6.95 (s, 1 H, Ar-H), 6.93 (s, 1 H, Ar-H), 5.00 - 5.08 (m, 2H, 2x-CH2-C

[0260] 3) The high resolution mass spectrum characteristics of the compound:

[0261] Using electrospray ionization: calcd for C 40 H 32 N2O4Na + ,([M+Na] + )627.2260, found 627.2253.

[0262] The physicochemical properties of compound IV-7 are as follows:

[0263] 1) Light yellow solid, melting point 100.1 - 100.8 °C;

[0264] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0265] In deuterated chloroform as solvent, TMS as internal standard, the peaks are as follows: 1 H NMR (400 MHz, CDC13): δ = 7.87 (s, 1 H, Ar-H), 7.85 (s, 1 H, Ar-H), 7.82 (s, 2H, Ar-H), 7.64 (s, 1 H, Ar-H), 7.62 (s, 1 H, Ar-H), 7.45 - 7.49 (m, 2H, Ar-H), 7.14 - 7.17 (m, 4H, Ar-H), 6.97 (s, 2H, 2x-OH), 6.95 (s, 1 H, Ar-H), 6.93 (s, 1 H, Ar-H), 5.00 - 5.08 (m, 2H, 2x-CH2-C H -CH2-), 3.39 (dd, J = 10.4, 16.4 Hz, 2H), 3.01 - 3.10 (m, 4H), 2.96 (dd, J = 6.0, 14.0 Hz, 2H). 13C NMR (100 MHz, CDC13): δ = 155.4, 153.2, 133.5, 132.7, 132.6, 131.2, 130.9, 130.7, 130.4, 130.0, 129.6, 125.5, 118.4, 117.4, 113.2, 82.9, 40.4, 39.2, 31.3.

[0266] 3) The high resolution mass spectrum of this compound is characterized as:

[0267] Using electrospray ionization: calcd for C 34 H 26 N4O4Na + , ([M+Na] + ) 577.1852, found 577.1850.

[0268] The physicochemical properties of compound IV-8 are as follows:

[0269] 1) Yellow solid, melting point 97.2-97.9 °C;

[0270] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0271] In deuterated chloroform as solvent, TMS as internal standard, the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.63 (s, 2H, Ar-H), 7.39-7.44 (m, 4H, Ar-H), 7.14 (d, J = 8.0 Hz, 4H, Ar-H), 6.93 (s, 1H, Ar-H), 6.91 (s, 1H, Ar-H), 4.95-5.03 (m, 2H, 2 x -CH2-C H -CH2-), 3.27-3.34 (m, 2H), 2.98-3.04 (m, 4H), 2.87-2.92 (m, 2H). 13 C NMR (100 MHz, CDC13): δ = 155.4, 152.2, 134.5, 133.4, 132.6, 131.1, 130.8, 129.8, 129.7, 128.7, 126.0, 125.2, 117.5, 82.8, 40.4, 39.4.

[0272] 3) The high resolution mass spectrum of this compound is characterized as:

[0273] Using electrospray ionization: calcd for C 32 H 25 N2O4 35 Cl4 + , ([M+H] +)641.0568, found 641.0571.

[0274] The physicochemical properties of compound IV-9 are as follows:

[0275] 1) White solid, melting point 83.7-84.5°C;

[0276] 2) The nuclear magnetic resonance spectrum characteristics of the compound are as follows:

[0277] In deuterated chloroform as solvent, TMS as internal standard, wherein the peak assignment is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.31-7.37 (m, 6H, Ar-H), 7.16 (d, J = 8.4 Hz, 4H, Ar-H), 7.05-7.09 (m, 2H, Ar-H), 6.96 (s, 2H, Ar-H), 6.94 (s, 2H, 2 x -OH), 4.96-5.03 (m, 2H, 2 x -CH2-C H -CH2-), 3.38 (dd, J = 10.4, 16.8 Hz, 2H), 3.01-3.08 (m, 4H), 2.92 (dd, J = 6.0, 14.0 Hz, 2H). 13 C NMR (100 MHz, CDC13): δ = 164.2, 161.8, 156.4, 156.3, 152.1, 132.6, 131.7, 131.6, 130.8, 130.7, 130.6, 129.8, 125.3, 122.8, 122.7, 117.6, 117.5, 117.3, 113.9, 113.7, 82.5, 40.4, 39.6, 27.2.

[0278] 3) The high resolution mass spectrum characteristics of the compound are as follows:

[0279] Using electrospray ionization: calcd for C 32 H 26 N2O4F2Na + , ([M+Na] + ) 563.1758, found 563.1765.

[0280] The physicochemical properties of compound IV-10 are as follows:

[0281] 1) White solid, melting point 97.0-97.5°C;

[0282] 2) The nuclear magnetic resonance spectrum characteristics of the compound are as follows:

[0283] In deuterated chloroform as solvent, TMS as internal standard, wherein the peak assignment is as follows: 1H NMR (600 MHz, CDC13): δ = 7.52 (d, J = 1.6 Hz, 2H, Ar-H), 7.51 (d, J = 1.6 Hz, 2H, Ar-H), 7.32 (d, J = 1.2 Hz, 2H, Ar-H), 7.31 (d, J = 1.2 Hz, 2H, Ar-H), 7.12 - 7.15 (m, 4H, Ar-H), 6.94 (s, 1H, Ar-H), 6.93 (s, 1H, Ar-H), 6.89 (s, 2H, 2 x -O H ), 4.94 - 4.99 (m, 2H, 2 x -CH2-C H -CH2-), 3.34 (dd, J = 10.0, 16.8 Hz, 2H), 3.00 - 3.05 (m, 4H), 2.90 (dd, J = 6.0, 14.4 Hz, 2H). 13 C NMR (150 MHz, CDC13): δ = 156.3, 152.2, 136.5, 132.6, 130.8, 129.9, 129.3, 128.2, 128.1, 125.2, 117.5, 82.4, 40.5, 40.4, 39.7.

[0284] 3) The high resolution mass spectrum characteristics of the compound:

[0285] Using electrospray ionization: calcd for C 32 H 26 N2O4 35 Cl2Na + , ([M+Na] + ) 595.1167, found 595.1165.

[0286] The physicochemical properties of compound IV-11 are as follows:

[0287] 1) White solid, melting point 92.2 - 92.7 °C;

[0288] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0289] With deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.44 - 7.49 (m, 8H, Ar-H), 7.15 (d, J = 7.2 Hz, 4H, Ar-H), 6.95 (s, 1H, Ar-H), 6.93 (s, 1H, Ar-H), 6.81 (s, 2H, 2 x -O H ), 4.94 - 5.01 (m, 2H, 2 x -CH2-C H-CH2-),3.36(dd,J=10.4,16.8Hz,2H),3.01–3.06(m,4H),2.86–2.92(m,2H). 13 C NMR (100MHz, CDCl3): δ=156.4,152.2,132.6,132.3,130.7,129.8,128.6,128.4,125.4,125.3,124.8,117.5,82.5,40.5,39.6.

[0290] 3) High-resolution mass spectrometric characteristics of the compound:

[0291] Using electrospray ionization: calcd for C 32 H 26 N2O4 79 Br2Na + ,([M+Na] + )683.0157,found683.0152.

[0292] The physicochemical properties of compound V-1 are as follows:

[0293] 1) White solid, melting point 106.3–106.9°C;

[0294] 2) NMR spectrum characteristics of the compound:

[0295] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ = 7.93 (d, J = 2.0Hz, 1H, Ar-H), 7.83 (d, J = 2.0Hz, 1H, Ar-H), 7.73 (d, J = 1.2Hz, 1H, Ar-H) ,7.62–7.64(m,4H,Ar-H),7.52(d,J=1.6Hz,1H,Ar-H),7.40(d,J=4.8Hz,6H,Ar-H),5.06–5.12(m,1H,-CH2-C H -CH2-),4.99–5.04(m,1H,-CH2-C H -CH2-),3.98(s,3H,-OC H 3),3.53(s,3H,-OC H 3),3.44–3.51(m,2H),3.00–3.22(m,6H). 13C NMR (100 MHz, CDC13): δ = 157.0, 156.9, 152.0, 149.8, 145.0, 144.1, 136.9, 136.2, 135.0, 134.4, 134.2, 132.4, 130.6, 130.5, 129.5, 129.4, 129.1, 126.9, 125.8, 124.9, 81.0, 80.5, 63.1, 62.6, 54.0, 40.5, 40.1, 35.4, 35.3, 29.6.

[0296] 3) The high resolution mass spectrum of the compound is characterized as:

[0297] Using electrospray ionization: calcd for C 34 H 30 N4O8Na + , ([M+Na] + ) 645.1961, found 645.1967.

[0298] The physicochemical properties of compound V-2 are as follows:

[0299] 1) White solid, melting point 114.3-114.9 °C;

[0300] 2) The nuclear magnetic resonance spectrum of the compound is characterized as:

[0301] Using deuterated chloroform as the solvent and TMS as the internal standard, the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.92 (d, J = 2.4 Hz, 1H, Ar-H), 7.82 (d, J = 2.4 Hz, 1H, Ar-H), 7.72 (d, J = 1.6 Hz, 1H, Ar-H), 7.51-7.54 (m, 5H, Ar-H), 7.20 (s, 2H, Ar-H), 7.18 (s, 2H, Ar-H), 5.03-5.09 (m, 1H, -CH2-C H -CH2-), 4.96-5.02 (m, 1H, -CH2-C H -CH2-), 3.98 (s, 3H, -OC H 3), 3.53 (s, 3H, -OC H 3), 3.41-3.51 (m, 2H), 2.98-3.21 (m, 6H), 2.37 (s, 6H, 2x-C H 3). 13C NMR (100 MHz, CDC13): δ = 156.6, 156.5, 151.7, 149.5, 144.7, 143.8, 140.6, 140.5, 136.6, 135.9, 134.8, 134.1, 134.0, 132.1, 129.5, 126.6, 126.5, 126.4, 126.3, 125.5, 124.6, 80.6, 80.1, 62.8, 62.3, 40.2, 39.9, 35.1, 35.0, 21.4.

[0302] 3) The high resolution mass spectrum of this compound is characterized by:

[0303] Using electrospray ionization: calcd for C 36 H 34 N4O8Na + , ([M+Na] + ) 673.2274, found 673.2277.

[0304] The physicochemical properties of compound V-3 are as follows:

[0305] 1) White solid, melting point 129.8-130.5 °C;

[0306] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0307] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.92 (d, J = 2.4 Hz, 1H, Ar-H), 7.82 (d, J = 1.2 Hz, 1H, Ar-H), 7.72 (d, J = 1.6 Hz, 1H, Ar-H), 7.51 (d, J = 1.6 Hz, 1H, Ar-H), 7.43 (d, J = 4.8 Hz, 2H, Ar-H), 7.32-7.35 (m, 2H, Ar-H), 7.15 (s, 1H, Ar-H), 7.13 (s, 1H, Ar-H), 5.02-5.08 (m, 1H, -CH2-C H -CH2-), 4.95-5.01 (m, 1H, -CH2-C H -CH2-), 3.98 (s, 3H, -OC H 3), 3.53 (s, 3H, -OC H 3), 3.40-3.50 (m, 2H), 2.97-3.21 (m, 6H), 2.27 (s, 12H, 4x -C H 3). 13C NMR (100 MHz, CDC13): δ = 156.7, 156.6, 151.7, 149.5, 144.7, 143.8, 139.3, 139.2, 137.1, 136.6, 135.9, 134.8, 134.1, 134.0, 132.1, 130.0, 127.7, 126.8, 126.7, 125.5, 124.6, 124.2, 80.5, 80.0, 62.8, 62.3, 40.2, 40.0, 35.1, 35.0, 19.8, 19.7.

[0308] 3) The high resolution mass spectrum of this compound is characterized by:

[0309] Using electrospray ionization: calcd for C 38 H 38 N4O8Na + , ([M+Na] + ) 701.2587, found 701.2591.

[0310] The physicochemical properties of compound V-4 are as follows:

[0311] 1) Light yellow solid, melting point 113.8-114.4 °C;

[0312] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0313] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 7.94 (d, J = 2.0 Hz, 1H, Ar-H), 7.83 (d, J = 2.0 Hz, 1H, Ar-H), 7.72 (d, J = 1.6 Hz, 1H, Ar-H), 7.55-7.58 (m, 4H, Ar-H), 7.52 (d, J = 1.6 Hz, 1H, Ar-H), 7.26 (s, 2H, Ar-H), 7.24 (s, 2H, Ar-H), 5.04-5.10 (m, 1H, -CH2-C H -CH2-), 4.96-5.02 (m, 1H, -CH2-C H -CH2-), 3.98 (s, 3H, -OC H 3), 3.53 (s, 3H, -OC H 3), 3.42-3.49 (m, 2H), 3.15-3.21 (m, 2H), 3.02-3.12 (m, 4H), 2.87-2.97 (m, 2H, 2x- C H -CH3), 1.26 (d, J = 1.6 Hz, 6H, 2x-CH-CH 3), 1.24 (d, J = 1.6 Hz, 6H, 2x-CH-C H 3). 13 CNMR (100 MHz, CDC13): δ = 156.6, 156.5, 151.7, 151.5, 151.4, 149.5, 144.7, 143.8, 136.6, 135.9, 134.7, 134.1, 134.0, 132.1, 126.9, 126.8, 126.7, 125.5, 124.6, 80.5, 80.0, 62.8, 62.3, 40.2, 39.9, 35.1, 35.0, 34.1, 23.8.

[0314] 3) The high resolution mass spectrum of this compound is characterized by:

[0315] Using electrospray ionization: calcd for C 40 H 42 N4O8Na + , ([M+Na] + ) 729.2900, found 729.2901.

[0316] The physical and chemical properties of compound V-5 are as follows:

[0317] 1) White solid, melting point 124.6-125.1 °C;

[0318] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0319] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 7.94 (d, J = 2.0 Hz, 1H, Ar-H), 7.83 (d, J = 2.0 Hz, 1H, Ar-H), 7.73 (d, J = 2.0 Hz, 1H, Ar-H), 7.55-7.59 (m, 4H, Ar-H), 7.52 (d, J = 1.2 Hz, 1H, Ar-H), 7.43 (d, J = 1.2 Hz, 2H, Ar-H), 7.41 (d, J = 1.2 Hz, 2H, Ar-H), 5.04-5.10 (m, 1H, -CH2-C H -CH2-), 4.96-5.02 (m, 1H, -CH2-C H -CH2-), 3.98 (s, 3H, -OC H 3), 3.53 (d, J = 1.6 Hz, 3H, -OC H3), 3.43-3.49 (m, 2H), 2.98-3.21 (m, 6H), 1.32 (s, 9H, 3x-C-C H 3), 1.31 (s, 9H, 3x-C-C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.5, 156.4, 153.8, 153.7, 151.7, 149.5, 144.7, 143.8, 136.6, 136.0, 134.8, 134.1, 134.0, 132.1, 126.5, 126.4, 126.3, 125.7, 125.5, 124.6, 80.6, 80.1, 62.8, 62.3, 40.2, 39.9, 39.8, 35.1, 35.0, 34.9, 31.1.

[0320] 3) The high resolution mass spectrum of this compound is characterized as:

[0321] Using electrospray ionization: calcd for C 42 H 46 N4O8Na + , ([M+Na] + ) 757.3213, found 757.3204.

[0322] The physicochemical properties of compound V-6 are as follows:

[0323] 1) White solid, melting point 133.5-134.1 °C;

[0324] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0325] Using deuterated chloroform as solvent and TMS as internal standard, the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.94 (d, J = 2.4 Hz, 1H, Ar-H), 7.91-7.92 (m, 1H, Ar-H), 7.90 (d, J = 1.6 Hz, 1H, Ar-H), 7.86 (s, 2H, Ar-H), 7.83-7.84 (m, 5H, Ar-H), 7.81 (s, 2H, Ar-H), 7.75 (d, J = 2.0 Hz, 1H, Ar-H), 7.53-7.54 (m, 1H, Ar-H), 7.48-7.52 (m, 4H, Ar-H), 5.10-5.16 (m, 1H, -CH2-C H -CH2-), 5.02-5.08 (m, 1H, -CH2-C H -CH2-), 4.00 (s, 3H, -OC H3), 3.56 - 3.63 (m, 2H), 3.53 (s, 3H, -OC H 3), 3.02 - 3.30 (m, 6H). 13 C NMR (100 MHz, CDC13): δ = 157.1, 157.0, 152.0, 149.8, 145.1, 144.1, 136.9, 136.2, 135.1, 134.4, 134.2, 133.3, 133.2, 132.5, 129.0, 128.9, 128.7, 128.2, 127.6, 127.3, 127.2, 127.1, 125.8, 124.8, 123.7, 81.2, 80.7, 63.1, 62.6, 40.5, 40.0, 35.4.

[0326] 3) The high resolution mass spectrum of this compound is characterized as:

[0327] Using electrospray ionization: calcd for C 42 H 34 N4O8Na + , ([M+Na] + ) 745.2274, found 745.2264.

[0328] The physicochemical properties of compound V-7 are as follows:

[0329] 1) White solid, melting point 129.8 - 130.4 °C;

[0330] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0331] Using deuterated chloroform as solvent and TMS as internal standard, the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.96 (d, J = 2.0 Hz, 1H, Ar-H), 7.93 (s, 1H, Ar-H), 7.91 (s, 1H, Ar-H), 7.89 (s, 2H, Ar-H), 7.85 (d, J = 2.0 Hz, 1H, Ar-H), 7.75 (d, J = 2.0 Hz, 1H, Ar-H), 7.70 (s, 1H, Ar-H), 7.68 (s, 1H, Ar-H), 7.52 - 7.56 (m, 3H, Ar-H), 5.07 - 5.19 (m, 2H, 2 x -CH2-C H -CH2-), 3.99 (s, 3H, -OCH3), 3.58 (s, 3H, -OCH3), 3.52 - 3.56 (m, 1H), 3.46 - 3.50 (m, 1H), 3.05 - 3.23 (m, 6H). 13C NMR (100 MHz, CDC13): δ = 155.4, 155.3, 152.0, 149.9, 145.1, 144.0, 136.9, 136.2, 135.0, 134.1, 133.9, 133.7, 133.6, 132.3, 131.0, 130.9, 130.8, 130.4, 130.3, 130.1, 125.8, 125.0, 118.4, 113.4, 81.8, 81.3, 63.1, 62.7, 40.4, 39.6, 35.4, 32.1.

[0332] 3) The high resolution mass spectrum of this compound is characterized by:

[0333] Using electrospray ionization: calcd for C 36 H 28 N6O8Na + , ([M+Na] + ) 695.1866, found 695.1870.

[0334] The physicochemical properties of compound V-8 are as follows:

[0335] 1) White solid, melting point 134.5-134.9 °C;

[0336] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0337] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 7.95 (d, J = 2.0 Hz, 1H, Ar-H), 7.82 (d, J = 2.4 Hz, 1H, Ar-H), 7.73 (d, J = 2.0 Hz, 1H, Ar-H), 7.70 (d, J = 1.2 Hz, 2H, Ar-H), 7.51 (d, J = 2.0 Hz, 1H, Ar-H), 7.49 (d, J = 1.6 Hz, 1H, Ar-H), 7.46-7.48 (m, 3H, Ar-H), 5.02-5.14 (m, 2H, 2 x -CH2-C H -CH2-), 3.98 (s, 3H, -OC H 3), 3.57 (s, 3H, -OC H 3), 3.40-3.50 (m, 2H), 3.01-3.21 (m, 6H). 13C NMR (100 MHz, CDC13): δ = 154.9, 154.8, 151.7, 149.6, 144.8, 143.8, 136.6, 135.7, 134.7, 134.4, 134.3, 133.8, 133.6, 133.1, 132.1, 130.8, 129.3, 129.2, 128.4, 128.3, 125.7, 125.5, 124.7, 81.3, 80.8, 62.8, 62.4, 40.1, 39.4, 35.1.

[0338] 3) The high resolution mass spectrum of this compound is characterized by:

[0339] Using electrospray ionization: calcd for C 34 H 26 N4O8Na 35 Cl4 + ,([M+Na] + ) 781.0402, found 781.0403.

[0340] The physicochemical properties of compound VI-1 are as follows:

[0341] 1) Light yellow solid, melting point 112.1-112.8 °C;

[0342] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0343] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 7.80 (s, 2H, Ar-H), 7.62-7.64 (m, 4H, Ar-H), 7.54 (s, 2H, Ar-H), 7.40 (d, J = 4.4 Hz, 6H, Ar-H), 4.98-5.05 (m, 2H, 2 x -CH2-C H -CH2-), 3.55 (s, 6H, 2 x -OCH3), 3.46-3.53 (m, 2H), 3.05-3.12 (m, 6H). 13 C NMR (100 MHz, CDC13): δ = 156.8, 150.2, 144.4, 137.2, 133.7, 132.8, 130.6, 129.5, 129.1, 126.9, 126.4, 81.0, 62.6, 40.3, 39.9.

[0344] 3) The high resolution mass spectrum of this compound is characterized by:

[0345] Using electrospray ionization: calcd for C 34 H30 N4O8Na + ,([M+Na] + )645.1961,found 645.1967.

[0346] The physicochemical properties of compound VI-2 are as follows:

[0347] 1) light yellow solid, melting point 124.8-125.7℃;

[0348] 2) the nuclear magnetic resonance spectrum characteristics of the compound:

[0349] In deuterated chloroform as solvent, TMS as internal standard, wherein the peak assignment is: 1 H NMR (400 MHz, CDC13): δ = 7.80 (s, 2H, Ar-H), 7.50-7.58 (m, 6H, Ar-H), 7.21 (s, 2H, Ar-H), 7.19 (s, 2H, Ar-H), 4.95-5.03 (m, 2H, 2x-CH2-C H -CH2-), 3.55 (s, 3H, -OC H 3), 3.54 (s, 3H, -OC H 3), 3.50 (dd, J = 10.4, 16.4 Hz, 2H), 2.99-3.09 (m, 6H), 2.37 (s, 6H, 2x-C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.4, 149.9, 144.1, 140.6, 136.9, 133.5, 133.4, 132.6, 129.5, 126.6, 126.4, 126.1, 80.5, 62.3, 40.1, 39.8, 21.4.

[0350] 3) the high resolution mass spectrum characteristics of the compound:

[0351] Using electrospray ionization: calcd for C 36 H 34 N4O8Na + ,([M+Na] + )673.2274, found 673.2275.

[0352] The physicochemical properties of compound VI-3 are as follows:

[0353] 1) white solid, melting point 114.3-115.0℃;

[0354] 2) the nuclear magnetic resonance spectrum characteristics of the compound:

[0355] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ=7.79(s,2H,Ar-H),7.53(s,2H,Ar-H),7.42(s,2H,Ar-H),7.34(s,1H ,Ar-H),7.32(s,1H,Ar-H),7.15(s,1H,Ar-H),7.13(s,1H,Ar-H),4.95–5.02(m,2H,2×-CH2-C H -CH2-),3.55(s,3H,-OC H 3),3.54(s,3H,-OC H 3),3.49(dd,J=10.4,16.4Hz,2H),2.98–3.09(m,6H),2.27(s,12H,4×-C H 3). 13 CNMR (100MHz, CDCl3): δ=156.6,149.9,144.1,139.3,137.1,136.9,133.5,133.4,1 32.6,130.0,127.7,126.7,126.1,124.2,80.4,62.3,40.1,39.8,39.7,19.8,19.7.

[0356] 3) High-resolution mass spectrometric characteristics of the compound:

[0357] Using electrospray ionization: calcd for C 38 H 38 N4O8Na + ,([M+Na] + )701.2587,found 701.2589.

[0358] The physicochemical properties of compound VI-4 are as follows:

[0359] 1) Pale yellow solid, melting point 118.0–118.9°C;

[0360] 2) NMR spectrum characteristics of the compound:

[0361] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1H NMR (400 MHz, CDC13): δ = 7.80 (d, J = 1.6 Hz, 2H, Ar-H), 7.57 (s, 2H, Ar-H), 7.54-7.55 (m, 4H, Ar-H), 7.43 (s, 2H, Ar-H), 7.40 (s, 2H, Ar-H), 4.96-5.03 (m, 2H, 2 x -CH2-C H -CH2-), 3.54 (s, 6H, 2 x -OC H 3), 3.51 (dd, J = 10.4, 16.4 Hz, 2H), 3.04-3.10 (m, 6H), 2.89-2.96 (m, 2H, 2 x -C H -CH3), 1.26 (d, J = 6.8 Hz, 12H, 4 x -CH-C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.4, 151.5, 149.9, 144.1, 136.9, 133.4, 132.6, 126.9, 126.7, 126.1, 80.5, 62.3, 40.0, 39.8, 34.1, 23.8.

[0362] 3) The high resolution mass spectrum of this compound is characterized:

[0363] Using electrospray ionization: calcd for C 40 H 42 N4O8Na + , ([M+Na] + ) 729.2900, found 729.2894.

[0364] The physicochemical properties of compound VI-5 are as follows:

[0365] 1) Light yellow solid, melting point 118.2-118.8 °C;

[0366] 2) The nuclear magnetic resonance spectrum of this compound is characterized:

[0367] In deuterated chloroform as solvent, TMS as internal standard, the assignment of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 7.80 (d, J = 1.6 Hz, 2H, Ar-H), 7.57 (s, 2H, Ar-H), 7.54-7.55 (m, 4H, Ar-H), 7.43 (s, 2H, Ar-H), 7.40 (s, 2H, Ar-H), 4.96-5.03 (m, 2H, 2 x -CH2-C H-CH2-), 3.55 (s, 3H, -OCH3), 3.54 (s, 3H, -OCH3), 3.48-3.51 (m, 1H), 3.44-3.47 (m, 1H), 3.03-3.10 (m, 6H), 1.32 (s, 18H, 6x-C-CH3). 13 C NMR (100 MHz, CDC13): δ = 156.4, 153.8, 149.9, 144.1, 136.9, 133.4, 132.6, 126.5, 126.3, 126.1, 125.7, 80.5, 62.3, 40.0, 39.7, 34.9, 31.1.

[0368] 3) The high resolution mass spectrum characteristics of the compound:

[0369] Using electrospray ionization: calcd for C 42 H 46 N4O8Na + , ([M+Na] + ) 757.3213, found 757.3209.

[0370] The physicochemical properties of compound VI-6 are as follows:

[0371] 1) Light yellow solid, melting point 130.0-130.6 °C;

[0372] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0373] In deuterated chloroform as solvent, TMS as internal standard, the peaks are as follows: 1 H NMR (400 MHz, CDC13): δ = 7.92 (s, 1H, Ar-H), 7.90 (s, 1H, Ar-H), 7.82-7.86 (m, 10H, Ar-H), 7.49-7.54 (m, 6H, Ar-H), 5.01-5.09 (m, 2H, 2x-CH2-C H -CH2-), 3.57-3.62 (m, 2H), 3.54 (s, 6H, 2x-OCH3), 3.16-3.22 (m, 2H), 3.02-3.10 (m, 4H). 13 C NMR (100 MHz, CDC13): δ = 156.6, 150.0, 144.1, 136.9, 134.0, 133.3, 132.9, 132.6, 128.6, 128.4, 128.2, 127.9, 127.3, 126.9, 126.8, 126.7, 126.1, 123.3, 80.8, 62.3, 40.1, 39.6.

[0374] 3) The high resolution mass spectrum of this compound is characterized by:

[0375] Using electrospray ionization: calcd for C 42 H 34 N4O8Na + , ([M+Na] + ) 745.2274, found 745.2266.

[0376] The physicochemical properties of compound VI-7 are as follows:

[0377] 1) White solid, melting point 130.2-130.9 °C;

[0378] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0379] In deuterated chloroform as solvent, TMS as internal standard, where each peak is assigned as: 1 H NMR (400 MHz, CDCl3): δ = 7.93 (s, 1H, Ar-H), 7.91 (s, 1H, Ar-H), 7.89 (s, 2H, Ar-H), 7.82 (d, J = 1.6 Hz, 2H, Ar-H), 7.71 (s, 1H, Ar-H), 7.69 (s, 1H, Ar-H), 7.57 (s, 3H, Ar-H), 7.55 (d, J = 8.0 Hz, 1H, Ar-H), 5.05-5.13 (m, 2H, 2 x -CH2-C H -CH2-), 3.60 (s, 6H, 2 x -OCH3), 3.52-3.55 (m, 1H), 3.48-3.51 (m, 1H), 3.07-3.14 (m, 6H). 13 C NMR (100 MHz, CDCl3): δ = 155.2, 150.3, 144.5, 137.2, 133.7, 133.4, 132.8, 130.9, 130.8, 130.3, 130.1, 126.4, 118.3, 113.5, 81.8, 62.6, 40.3, 39.5.

[0380] 3) The high resolution mass spectrum of this compound is characterized by:

[0381] Using electrospray ionization: calcd for C 36 H 28 N6O8Na + , ([M+Na] + ) 695.1866, found 695.1873.

[0382] The physicochemical properties of compound VI-8 are as follows:

[0383] 1) pale yellow solid, melting point 120.2-120.7 °C;

[0384] 2) the nuclear magnetic resonance spectrum of the compound is characterized by:

[0385] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 7.80 (d, J = 2.4 Hz, 2H, Ar-H), 7.69 (s, 2H, Ar-H), 7.53 (d, J = 2.4 Hz, 2H, Ar-H), 7.48 (s, 4H, Ar-H), 5.01-5.08 (m, 2H, 2x-CH2-C H -CH2-), 3.59 (s, 6H, 2x-OC H 3), 3.49 (dd, J = 10.4, 16.4 Hz, 2H, Ar-H), 3.01-3.07 (m, 6H). 13 C NMR (100 MHz, CDC13): δ = 154.8, 150.0, 144.2, 136.8, 134.4, 133.2, 133.1, 132.5, 130.9, 129.2, 128.4, 126.1, 125.6, 81.3, 62.3, 40.0, 39.4.

[0386] 3) the high resolution mass spectrum of the compound is characterized by:

[0387] Using electrospray ionization: calcd for C 34 H 26 N4O8Na 35 Cl4 + , ([M+Na] + ) 781.0402, found 781.0401.

[0388] The physicochemical properties of compound VII-1 are as follows:

[0389] 1) yellow solid, melting point 125.4-125.9 °C;

[0390] 2) the nuclear magnetic resonance spectrum of the compound is characterized by:

[0391] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned as: 1 H NMR (400 MHz, CDC13): δ = 11.10 (s, 1H, -O H ), 11.07 (s, 1H, -O H), 8.25 (s, 1H, Ar-H), 8.08 (s, 1H, Ar-H), 7.83 (s, 1H, Ar-H), 7.63-7.67 (m, 5H, Ar-H), 7.41 (s, 6H, Ar-H), 5.11-5.19 (m, 1H, -CH2-C H -CH2-), 4.98-5.06 (m, 1H, -CH2-C H -CH2-), 3.53 (dd, J = 10.0, 16.4 Hz, 2H), 3.14-3.23 (m, 3H), 3.00-3.11 (m, 3H). 13 C NMR (100 MHz, CDC13): δ = 157.0, 156.9, 153.4, 151.8, 140.6, 139.7, 134.2, 133.8, 130.6, 130.5, 130.4, 129.8, 129.7, 129.5, 129.1, 129.0, 128.7, 127.8, 127.0, 125.5, 124.7, 81.2, 79.9, 40.3, 40.2, 40.0, 35.6.

[0392] 3) The high resolution mass spectrum characteristics of the compound:

[0393] Using electrospray ionization: calcd for C 32 H 26 N4O8Na + , ([M+Na] + ) 617.1648, found 617.1650.

[0394] The physicochemical properties of compound VII-2 are as follows:

[0395] 1) Light yellow solid, melting point 128.5-129.1 °C;

[0396] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0397] In deuterated chloroform as solvent, TMS as internal standard, the peaks are as follows: 1HNMR (400 MHz, CDC13): δ = 11.08 (s, 1H, -OH), 11.06 (s, 1H, -OH), 8.24 (s, 1H, Ar-H), 8.08 (s, 1H, Ar-H), 7.83 (s, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.56 (s, 1H, Ar-H), 7.54 (s, 2H, Ar-H), 7.52 (s, 1H, Ar-H), 7.21 (d, J = 2.4 Hz, 2H, Ar-H), 7.19 (d, J = 2.0 Hz, 2H, Ar-H), 5.09 - 5.16 (m, 1H, -CH2-C H -CH2-), 4.95 - 5.03 (m, 1H, -CH2-C H -CH2-), 3.50 (dd, J = 10.4, 16.4 Hz, 2H), 3.16 - 3.20 (m, 2H), 3.02 - 3.14 (m, 4H), 2.37 (s, 3H, -CH3), 2.36 (s, 3H, -CH3). 13 C NMR (100 MHz, CDC13): δ = 156.6, 156.5, 153.1, 151.5, 140.6, 140.5, 140.3, 139.4, 133.9, 133.5, 130.2, 129.5, 129.4, 128.4, 127.5, 126.6, 126.4, 125.1, 124.4, 80.7, 79.4, 40.0, 39.9, 39.8, 35.2, 21.4.

[0398] 3) The high resolution mass spectrum characteristics of the compound:

[0399] Using electrospray ionization: calcd for C 34 H 30 N4O8Na + , ([M+Na] + ) 645.1961, found 645.1968.

[0400] The physicochemical properties of compound VII-3 are as follows:

[0401] 1) Yellow solid, melting point 135.5 - 136.3 °C;

[0402] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0403] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1HNMR (400 MHz, CDC13): δ = 11.08 (s, 1H, -OH), 11.06 (s, 1H, -OH), 8.24 (s, 1H, Ar-H), 8.07 (s, 1H, Ar-H), 7.83 (s, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.46 (s, 1H, Ar-H), 7.43 (s, 1H, Ar-H), 7.33-7.37 (m, 2H, Ar-H), 7.16 (d, J = 2.8 Hz, 1H, Ar-H), 7.14 (d, J = 2.8 Hz, 1H, Ar-H), 5.08-5.15 (m, 1H, -CH2-C H -CH2-), 4.94-5.02 (m, 1H, -CH2-C H -CH2-), 3.49 (dd, J = 10.4, 16.8 Hz, 2H), 3.16-3.21 (m, 2H), 2.97-3.13 (m, 4H), 2.27 (s, 12H, 4x-CH3). 13 C NMR (100 MHz, CDC13): δ = 156.7, 156.6, 153.1, 151.5, 140.3, 139.4, 139.3, 139.2, 137.1, 137.0, 133.9, 133.5, 130.1, 130.0, 129.5, 128.4, 127.7, 127.5, 126.9, 126.7, 125.1, 124.4, 124.3, 124.2, 80.6, 79.3, 40.0, 39.9, 35.2, 19.8, 19.7, 19.6.

[0404] 3) The high resolution mass spectrum of this compound is characterized as:

[0405] calcd for C 36 H 34 N4O8Na + , ([M+Na] + ) 673.2274, found 673.2277.

[0406] The physicochemical properties of compound VII-4 are as follows:

[0407] 1) Yellow solid, melting point 140.6-141.3 °C;

[0408] 2) The nuclear magnetic resonance spectrum of this compound is characterized as:

[0409] In deuterated chloroform as solvent, TMS as internal standard, the attribution of each peak is as follows: 1HNMR (400MHz, CDCl3): δ=11.08(s,1H,-OH),11.06(s,1H,-OH),8.24–8.25(m,1H,Ar-H),8.08(d,J=1.6Hz,1H,Ar-H),7.83(s,1H,Ar -H),7.62(s,1H,Ar-H),7.60(s,1H,Ar-H),7.58(s,2H,Ar-H),7.56(s,1H,Ar-H),7.24–7.27(m,4H,Ar-H),5.08–5.16(m,1H,-CH2-C H -CH2-),4.95–5.03(m,1H,-CH2-C H -CH2-),3.50(dd,J=10.4,16.8Hz,2H),3.13–3.20(m,3H),3.02–3.09(m,3H),2.89–2.96(m,2H,2×-C H -CH3),1.26(d,J=1.6Hz,6H,2×-CH-C H 3),1.24(d,J=1.6Hz,6H,2×-CH-C H 3). 13 C NMR (100MHz, CDCl3): δ=156.6,156.5,153.1,151.5,151.4,140.3,139.4,133.9,133.5,130.2,129.5,1 28.4,127.5,127.0,126.9,126.8,126.7,125.1,124.4,80.7,79.4,40.0,39.9,39.8,35.2,34.1,23.8.

[0410] 3) High-resolution mass spectrometric characteristics of the compound:

[0411] Using electrospray ionization: calcd for C 38 H 38 N4O8Na + ,([M+Na] + )701.2587,found 701.2588.

[0412] The physicochemical properties of compound VII-5 are as follows:

[0413] 1) Yellow solid, melting point 145.6–146.0°C;

[0414] 2) NMR spectrum characteristics of the compound:

[0415] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 HNMR (400MHz, CDCl3): δ = 11.08 (s, 1H, -OH), 11.06 (s, 1H, -OH), 8.24–8.25 (m ,1H,Ar-H),8.08(d,J=1.6Hz,1H,Ar-H),7.83–7.84(m,1H,Ar-H),7.62–7.63 (m,1H,Ar-H),7.61(s,1H,Ar-H),7.59(s,1H,Ar-H),7.57(s,1H,Ar-H),7.43 (d,J=2.4Hz,2H,Ar-H),7.41(d,J=2.4Hz,2H,Ar-H),5.08–5.16(m,1H,-CH2-C H -CH2-),4.96–5.03(m,1H,-CH2-C H -CH2-),3.44–3.51(m,2H),3.08–3.21(m,3H),2.98–3.06(m,3H),1.32(s,9H,3×-C-CH3),1.31(s,9H,3×-C-CH3). 13 C NMR (100MHz, CDCl3): δ=156.5,156.4,153.7,153.6,153.1,151.5,140.3,139.4,133.9,133.5,130.2,129.5,1 28.4,127.5,126.6,126.5,126.4,125.8,125.7,125.2,124.4,80.7,79.4,40.0,39.9,35.2,34.9,31.2,26.9.

[0416] 3) High-resolution mass spectrometric characteristics of the compound:

[0417] Using electrospray ionization: calcd for C 40 H 42 N4O8Na + ,([M+Na] + )729.2900,found 729.2897.

[0418] The physicochemical properties of compound VII-6 are as follows:

[0419] 1) Yellow solid, melting point 144.3–145.1°C;

[0420] 2) NMR spectrum characteristics of the compound:

[0421] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 HNMR (400MHz, CDCl3): δ = 11.10 (s, 1H, -OH), 11.07 (s, 1H, -OH), 8.26 (d, J = 2.4Hz, 1H, Ar-H), 8.10 (d, J = 2.0Hz, 1H, Ar-H), 7.92–7.96 (m ,2H,Ar-H),7.89(s,1H,Ar-H),7.81–7.85(m,8H,Ar-H),7.65(d,J=2.0Hz,1H,Ar-H),7.49–7.51(m,4H,Ar-H),5.15–5.23(m,1H,-CH2-C H -CH2-),5.03–5.10(m,1H,-CH2-C H -CH2-),3.63(dd,J=10.4,16.4Hz,2H),3.13–3.31(m,4H),3.03–3.11(m,2H). 13 C NMR (100MHz, CDCl3): δ=156.8,156.7,153.1,151.5,140.3,139.4,134.1,133.9,133.5,133.0,132.9,130.2,129.4,128.7,128 .6,128.4,127.9,127.3,127.2,127.0,126.8,125.2,124.4,123.5,123.4,81.0,79.8,40.0,39.8,39.6,35.2,31.6,26.9,22.7.

[0422] 3) High-resolution mass spectrometric characteristics of the compound:

[0423] Using electrospray ionization: calcd for C 40 H 30 N4O8Na + ,([M+Na] + )717.1961,found 717.1959.

[0424] The physicochemical properties of compound VII-7 are as follows:

[0425] 1) Yellow solid, melting point 150.4–151.1°C;

[0426] 2) NMR spectrum characteristics of the compound:

[0427] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1HNMR (400 MHz, CDC13): δ = 11.11 (s, 1H, -OH), 11.09 (s, 1H, -OH), 8.26-8.27 (m, 1H, Ar-H), 8.09 (d, J = 2.0 Hz, 1H, Ar-H), 7.91-7.94 (m, 3H, Ar-H), 7.87 (d, J = 1.6 Hz, 1H, Ar-H), 7.85 (d, J = 2.4 Hz, 1H, Ar-H), 7.69-7.70 (m, 1H, Ar-H), 7.67-7.68 (m, 1H, Ar-H), 7.63-7.64 (m, 1H, Ar-H), 7.52-7.56 (m, 2H, Ar-H), 5.18-5.26 (m, 1H, -CH2-C H -CH2-), 5.06-5.13 (m, 1H, -CH2-C H -CH2-), 3.53 (dd, J = 10.4, 16.8 Hz, 2H), 3.06-3.27 (m, 6H). 13 C NMR (100 MHz, CDC13): δ = 155.0, 154.9, 153.1, 151.6, 140.2, 139.2, 133.9, 133.6, 133.4, 133.3, 130.9, 130.7, 130.6, 130.2, 130.1, 129.8, 129.7, 129.0, 128.0, 127.5, 125.2, 124.5, 118.1, 118.0, 113.3, 113.2, 81.6, 80.4, 39.9, 39.4, 39.2, 35.2, 29.7.

[0428] 3) The high resolution mass spectrum of the compound is characterized as follows:

[0429] Using electrospray ionization: calcd for C 34 H 24 N6O8Na + , ([M+Na] + ) 667.1553, found 667.1553.

[0430] The physicochemical properties of compound VII-8 are as follows:

[0431] 1) Yellow solid, melting point 156.3-157.1 °C;

[0432] 2) The nuclear magnetic resonance spectrum of the compound is characterized as follows:

[0433] In deuterated chloroform as solvent, TMS as internal standard, the attribution of each peak is as follows: 1HNMR (400 MHz, CDC13): δ = 11.10 (s, 1H, -O H ), 11.09 (s, 1H, -O H ), 8.26 (s, 1H, Ar-H), 8.08 (s, 1H, Ar-H), 7.83 (s, 1H, Ar-H), 7.72 (s, 1H, Ar-H), 7.69 (s, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.46-7.51 (m, 4H, Ar-H), 5.14-5.21 (m, 1H, -CH2-C H -CH2-), 5.02-5.09 (m, 1H, -CH2-C H -CH2-), 3.42-3.48 (m, 2H), 3.01-3.24 (m, 6H). 13 CNMR (100 MHz, CDC13): δ = 155.0, 154.8, 153.1, 151.6, 140.2, 139.3, 134.4, 134.3, 133.9, 133.5, 133.2, 130.9, 130.2, 129.4, 129.1, 128.4, 128.1, 127.5, 125.7, 125.2, 124.5, 81.4, 80.2, 39.9, 39.5, 39.3.

[0434] 3) The high resolution mass spectrum characteristics of the compound:

[0435] Using electrospray ionization: calcd for C 32 H 22 N4O8Na 35 Cl4 + , ([M+Na] + ) 753.0089, found 753.0082.

[0436] The physicochemical properties of compound VIII-1 are as follows:

[0437] 1) Yellow solid, melting point 136.0-136.5°C;

[0438] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0439] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 10.86 (s, 2H, 2 x -O HH), 7.59 (s, 2H, Ar-H), 7.54 (s, 2H, Ar-H), 7.52 (s, 2H, Ar-H), 7.21 (s, 2H, Ar-H), 7.19 (s, 2H, Ar-H), 4.95-5.02 (m, 2H, 2 x -CH2-C H -CH2-), 3.49 (dd, J = 10.0, 16.4 Hz, 2H), 2.97-3.10 (m, 6H), 2.37 (s, 6H, 2 x -C 13 C NMR (100 MHz, CDC13): δ = 156.9, 152.2, 140.9, 134.0, 130.6, 129.6, 129.2, 129.1, 127.5, 126.9, 125.9, 81.2, 60.7, 40.2, 39.9.

[0440] 3) The high resolution mass spectrum characteristics of the compound:

[0441] Calcd for C 32 H 26 N4O8Na + , ([M+Na] + ) 617.1648, found 617.1646.

[0442] The physicochemical properties of compound VIII-2 are as follows:

[0443] 1) Orange yellow solid, melting point 140.6-141.0 °C;

[0444] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0445] In deuterated chloroform as solvent, TMS as internal standard, the assignment of each peak is as follows: 1 H NMR (400 MHz, CDC13): δ = 10.85 (s, 2H, 2 x -O H ), 8.11 (s, 2H, Ar-H) 7.59 (s, 2H, Ar-H), 7.54 (s, 2H, Ar-H), 7.52 (s, 2H, Ar-H), 7.21 (s, 2H, Ar-H), 7.19 (s, 2H, Ar-H), 4.95-5.02 (m, 2H, 2 x -CH2-C H -CH2-), 3.49 (dd, J = 10.0, 16.4 Hz, 2H), 2.97-3.10 (m, 6H), 2.37 (s, 6H, 2 x -C H 3). 13C NMR (100 MHz, CDC13): δ = 156.5, 151.9, 140.6, 140.5, 133.7, 129.5, 128.9, 127.2, 126.6, 126.5, 125.5, 80.7, 39.9, 39.8, 26.9, 21.5.

[0446] 3) The high resolution mass spectrum of this compound is characterized by:

[0447] Using electrospray ionization: calcd for C 34 H 30 N4O8Na + , ([M+Na] + ) 645.1961, found 645.1965.

[0448] The physical and chemical properties of compound VIII-3 are as follows:

[0449] 1) Yellow solid, melting point 145.7-146.4 °C;

[0450] 2) The nuclear magnetic resonance spectrum of this compound is characterized by:

[0451] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 10.85 (s, 2H, 2 x -OH), 8.11 (s, 2H, Ar-H) 7.60 (s, 2H, Ar-H), 7.44 (s, 2H, Ar-H), 7.35 (s, 1H, Ar-H), 7.35 (s, 1H, Ar-H), 7.16 (s, 1H, Ar-H), 7.14 (s, 1H, Ar-H), 4.94-5.02 (m, 2H, 2 x -CH2-C H -CH2-), 3.48 (dd, J = 10.0, 16.4 Hz, 2H), 3.04-3.09 (m, 4H), 2.96-3.01 (m, 2H), 2.28 (s, 12H, 4 x -CH3). 13 CNMR (100 MHz, CDC13): δ = 156.6, 151.9, 140.6, 139.3, 137.1, 133.7, 130.0, 129.0, 127.7, 127.2, 126.8, 125.5, 124.2, 80.6, 39.9, 39.8, 19.8, 19.7.

[0452] 3) The high resolution mass spectrum of this compound is characterized by:

[0453] Using electrospray ionization: calcd for C 36 H34 N4O8Na + ,([M+Na] + )673.2274,found 673.2275.

[0454] The physicochemical properties of compound VIII-4 are as follows:

[0455] 1) light yellow solid, melting point 126.4-126.9℃;

[0456] 2) the nuclear magnetic resonance spectrum characteristics of the compound are as follows:

[0457] In deuterated chloroform as solvent, TMS as internal standard, wherein each peak is assigned as follows: 1 H NMR (400 MHz, CDC13): δ = 10.86 (s, 2H, 2 x -OH), 8.11 (d, J = 1.6 Hz, 2H, Ar-H) 7.61 (d, J = 2.0 Hz, 2H, Ar-H), 7.58 (s, 2H, Ar-H), 7.56 (s, 2H, Ar-H), 7.27 (s, 2H, Ar-H), 7.25 (s, 2H, Ar-H), 4.95-5.03 (m, 2H, 2 x -CH2-C H -CH2-), 3.50 (dd, J = 10.4, 16.4 Hz, 2H), 3.05-3.10 (m, 4H), 2.96-3.01 (m, 2H), 2.89-2.94 (m, 2H, 2 x -C H -CH3), 1.26 (d, J = 6.8 Hz, 12H, 4 x -CH-C H 3). 13 C NMR (100 MHz, CDC13): δ = 156.5, 151.9, 151.5, 140.6, 133.7, 128.9, 127.2, 126.9, 126.8, 126.7, 125.5, 80.7, 39.9, 39.8, 34.1, 23.8.

[0458] 3) the high resolution mass spectrum characteristics of the compound are as follows:

[0459] Using electrospray ionization: calcd for C 38 H 38 N4O8Na + ,([M+Na] + )701.2587,found 701.2586.

[0460] The physicochemical properties of compound VIII-5 are as follows:

[0461] 1) yellow solid, melting point 141.0-141.5℃;

[0462] 2) The compound's nuclear magnetic resonance spectrum characteristics:

[0463] In deuterated chloroform as solvent, TMS as internal standard, wherein the peak assignment is: 1 H NMR (400 MHz, CDC13): δ = 10.86 (s, 2H, 2 x -OH), 8.11 (d, J = 2.0 Hz, 2H, Ar-H), 7.61 (d, J = 2.0 Hz, 2H, Ar-H), 7.59 (s, 2H, Ar-H), 7.57 (s, 2H, Ar-H), 7.43 (s, 2H, Ar-H), 7.41 (s, 2H, Ar-H), 4.96-5.03 (m, 2H, 2 x -CH2-C H -CH2-), 3.50 (dd, J = 10.0, 16.4 Hz, 2H), 3.05-3.11 (m, 4H), 2.96-3.01 (m, 2H), 1.32 (s, 18H, 6 x -C-CH3). 13 C NMR (100 MHz, CDC13): δ = 156.4, 153.7, 151.9, 140.7, 133.7, 128.9, 127.2, 126.5, 126.4, 125.7, 125.5, 80.7, 39.9, 39.8, 34.9, 31.1.

[0464] 3) The compound's high resolution mass spectrum characteristics:

[0465] Using electrospray ionization: calcd for C 40 H 42 N4O8Na + , ([M+Na] + ) 729.2900, found 729.2895.

[0466] The compound VIII-6 physical and chemical properties are as follows:

[0467] 1) Yellow solid, melting point 152.4-152.9 °C;

[0468] 2) The compound's nuclear magnetic resonance spectrum characteristics:

[0469] In deuterated chloroform as solvent, TMS as internal standard, wherein the peak assignment is: 1H NMR (400 MHz, CDC13): δ = 10.85 (s, 2H, 2 x -OH), 8.12-8.14 (m, 2H, Ar-H), 7.94 (d, J = 1.2 Hz, 1H, Ar-H), 7.92 (d, J = 1.6 Hz, 1H, Ar-H), 7.81-7.86 (m, 8H, Ar-H), 7.60 (d, J = 2.4 Hz, 2H, Ar-H), 7.48-7.53 (m, 4H, Ar-H), 5.01-5.09 (m, 2H, 2 x -CH2-C H -CH2-), 3.61 (dd, J = 10.4, 16.4 Hz, 2H), 3.16-3.22 (m, 2H), 2.99-3.11 (m, 4H). 13 C NMR (100 MHz, CDC13): δ = 157.0, 152.2, 140.9, 134.4, 134.0, 133.2, 129.1, 128.9, 128.7, 128.2, 127.6, 127.3, 127.2, 127.1, 125.9, 123.7, 81.3, 40.2, 39.9, 30.0, 29.6.

[0470] 3) The high resolution mass spectrum characteristics of the compound:

[0471] Using electrospray ionization: calcd for C 40 H 31 N4O8 + , ([M+Na] + ) 695.2142, found 695.2134.

[0472] The physicochemical properties of compound VIII-7 are as follows:

[0473] 1) Yellow solid, melting point 140.1-140.8 °C;

[0474] 2) The nuclear magnetic resonance spectrum characteristics of the compound:

[0475] In deuterated chloroform as solvent, TMS as internal standard, wherein the peaks are assigned as follows: 1H NMR (400MHz, CDCl3): δ=10.89(s,2H,2×-OH),8.13(d,J=2.0Hz,2H,Ar-H),7.92(s,1H,Ar-H),7.90(s,1H,Ar-H),7.88(d,J=1.6H z,2H,Ar-H),7.70(s,1H,Ar-H),7.69(s,1H,Ar-H),7.60–7.62(m,2H,Ar-H),7.52–7.56(m,2H,Ar-H),5.06–5.13(m,2H,2×-CH2-C H -CH2-),3.50–3.53(m,1H),3.46–3.49(m,1H),3.02–3.12(m,6H). 13 C NMR (100MHz, CDCl3): δ=155.2,152.3,140.9,134.1,133.7,131.1,130.9, 130.4,130.1,128.8,127.6,126.0,118.4,113.6,82.0,40.2,39.4,30.0.

[0476] 3) High-resolution mass spectrometric characteristics of the compound:

[0477] Using electrospray ionization: calcd for C 34 H 24 N6O8Na + ,([M+Na] + )667.1553,found 667.1556.

[0478] The physicochemical properties of compound VIII-8 are as follows:

[0479] 1) Yellow solid, melting point 144.9–145.7°C;

[0480] 2) NMR spectrum characteristics of the compound:

[0481] Deuterated chloroform was used as solvent and TMS was used as internal standard. The peaks were assigned as follows: 1 H NMR (400MHz, CDCl3): δ = 10.88 (s, 2H, 2×-O H ),8.11(d,J=1.6Hz,2H,Ar-H),7.69(s,2H,Ar-H),7.59(s,2H,Ar-H),7.48(s,4H,Ar-H),5.02–5.09(m,2H,2×-CH2-C H-CH2-), 3.48 (dd, J = 10.4, 16.4 Hz, 2H), 3.01 - 3.10 (m, 6H). 13 C NMR (100 MHz, CDC13): δ = 154.8, 152.0, 140.5, 134.4, 133.8, 133.2, 130.8, 129.3, 128.5, 128.4, 127.2, 125.7, 125.6, 81.4, 39.8, 39.2.

[0482] 3) The high resolution mass spectrum of this compound is characterized:

[0483] Using electrospray ionization: calcd for C 32 H 23 N4O8 35 Cl4 + , ([M+Na] + ) 731.0270, found 731.0274.

[0484] Bioactivity assay of the isoxazoline-hybridized new lignan compounds prepared in Examples 1-76

[0485] 1. Test insects: Plutella xylostella and Mythimna separata larvae.

[0486] 2. Test samples and reagents:

[0487] The samples were isoxazoline-hybridized new lignan compounds I-1-11, II-1-11, III-1-11, IV-1-11, V-1-8, VI-1-8, VII-1-8 and VIII-1-8 prepared in Examples, and positive control agents rotenone and novaluron; the solvent was acetone.

[0488] 3. Bioassay method:

[0489] (1) Determination of stomach toxicity activity of Plutella xylostella

[0490] The stomach toxicity of all samples on the diamondback moth was tested by adding small leaf discs. A layer of filter paper was placed on the bottom of the culture dish and moistened with water. 15 healthy and active late second instar larvae of diamondback moth were selected for each dish and starved for 8 hours. The test samples were dissolved in acetone to prepare a solution with a concentration of 10 μg / mL. Fresh cabbage leaves were cut into 1 cm diameter leaf discs using a puncher and immersed in the test sample solution for 3-5 seconds. After the solvent was naturally evaporated, the test insects were fed. Each compound was set up in triplicate. A certain amount of treated leaf discs was fed to each repeat group, and the number of live insects was observed regularly. When the leaf discs were eaten, the corresponding toxic leaf discs were added. After 48 hours of feeding, fresh normal cabbage leaves were fed until the end of the pupation. The uniform acetone solution was used as a blank control group, and rotenone and azadirachtin were used as positive control agents. The temperature was controlled at 25±1°C and the humidity was maintained at 60-80% during the entire test period. The light / dark time was 12 hours / 12 hours. The number of live insects and poisoning symptoms were observed and recorded regularly. The mortality rate at different times (Formula-1) and the corrected mortality rate (Formula-2) were calculated according to the following formula. The results of the biological tests are shown in Table-2.

[0491]

[0492] Table-2 Stomach toxicity of isoxazoline hybridized neolignan compounds on diamondback moth larvae

[0493]

[0494]

[0495] (2) Stomach toxicity activity determination of oriental armyworm

[0496] Similarly, the small leaf disc addition method was used. A layer of filter paper was placed on the bottom of the culture dish and moistened with water. 10 healthy pre-third instar larvae of oriental armyworm were selected for each repeat, and starved for 12 hours. All test compounds were prepared into a 1 mg / mL acetone solution for standby. Fresh corn leaves were cut into 1x1 cm small leaf pieces after removing the main leaf veins, immersed in the test solution for 3-5 seconds, and then fed to the test insects after natural evaporation. Acetone was used as a blank control, and rotenone and azadirachtin were used as positive control agents. After the larvae ate the leaves, the corresponding toxic leaves were added. After 48 hours of feeding, normal leaves were fed until the end of the pupation. The temperature was maintained at 25±1°C and the humidity was maintained at 60-80% during the entire test period. The light / dark time was 12 hours / 12 hours. The number of dead insects and poisoning symptoms were observed and recorded regularly. The mortality rate at different times (Formula-1) and the corrected mortality rate (Formula-2) were calculated according to the following formula. The results of the biological tests are shown in Table-3.

[0497] Table-3. The stomach toxicity of isoxazoline hybridized new lignan compounds against P. xylostella

[0498]

[0499]

[0500] 4. Conclusion

[0501] The results of bioassay (Table-2) showed that the isoxazoline hybridized new lignan compounds (isoxazoline magnolol, isoxazoline and honokiol, isoxazoline nitrated magnolol, isoxazoline nitrated and honokiol derivatives) prepared by the present application showed obvious stomach toxicity against P. xylostella larvae; especially, the corrected mortality of derivatives III-3, IV-4, IV-6 and VII-4 against P. xylostella reached 100% at 72 hours, even more than two commercial insecticides rotenone and novaluron. Meanwhile, the 72-hour corrected mortality of derivatives I-4, II-3, II-4, II-6, II-11, III-2, III-4, III-5, III-6, III-7, IV-1, IV-3, IV-5, V-6 and VIII-8 also exceeded the commercial plant source insecticide rotenone.

[0502] The results of bioassay (Table-3) showed that the isoxazoline hybridized new lignan compounds (isoxazoline magnolol, isoxazoline and honokiol, isoxazoline nitrated magnolol, isoxazoline nitrated and honokiol derivatives) prepared by the present application showed obvious stomach toxicity against P. xylostella larvae, and the mortality of derivative I-9 against the test insects reached 100%, which was far more than the plant source insecticide rotenone and similar to the chemical insecticide novaluron, which indicated that the compound had great potential to be developed into a new insecticide. Meanwhile, the final corrected mortality of derivatives I-5, I-11, II-5, II-7, II-8, II-9, III-1, III-2, III-10, III-11, IV-1, IV-2, IV-9, IV-10, IV-11, VII-1, VII-3, VII-4 and VIII-7 against the test insects was also better than rotenone, which showed certain application value.

[0503] In summary, the isoxazoline hybridized new lignan compounds (isoxazoline magnolol, isoxazoline and honokiol, isoxazoline nitrated magnolol, isoxazoline nitrated and honokiol derivatives) in the present application can be used to prepare a new insecticide with high efficiency and applied to the prevention and control of P. xylostella and P. xylostella.

[0504] The specification and drawings of the present application are considered to be illustrative and not restrictive in character, and that within the scope of the application, changes and modifications can be suggested to one skilled in the art, and all such changes and modifications are considered to be within the scope of this application.

Claims

1. An isoxazoline hybridized lignan compound, characterized in that: The general chemical formula of the isoxazoline-hybridized lignan compound is shown in formula (I): In the formula (I), R 1 =OH or OMe; R 2 and R 3 =H or OH or OMe; R 4 =H or NO2; Ar is any of the following:

2. The method for preparing the isoxazoline hybridized lignan compound according to claim 1, wherein Using triethylamine as a base and dichloromethane as a solvent, the raw materials react with α-chlorooxime in a 1,3-dipolar cycloaddition reaction to obtain isoxazoline-hybridized lignan compounds. The general reaction formula is as follows: The R 1 , R 2 , R 3 , R 4 , Ar corresponds to claim 1.

3. The preparation method according to claim 2, characterized in that 1 mmol of the raw material was dissolved in 5 mL of dichloromethane, 5 mmol of triethylamine was added at 40°C, and then 4 mmol of α-chlorooxime was added. The reaction progress was tracked and detected. After the reaction was completed, the mixture was concentrated under reduced pressure and separated by preparative silica gel thin layer chromatography to obtain an isoxazoline hybrid lignan compound.

4. The preparation method according to claim 2 or 3, characterized in that The α-chlorooxime is one of α-chlorobenzaldehyde oxime, α-chloro-4-methylbenzaldehyde oxime, α-chloro-3,4-dimethylbenzaldehyde oxime, α-chloro-4-isopropylbenzaldehyde oxime, α-chloro-4-tert-butylbenzaldehyde oxime, α-chloro-2-naphthaldehyde oxime, α-chloro-3-cyanobenzaldehyde oxime, α-chloro-3,4-dichlorobenzaldehyde oxime, α-chloro-3-fluorobenzaldehyde oxime, α-chloro-4-chlorobenzaldehyde oxime or α-chloro-4-bromobenzaldehyde oxime.

5. The use of the isoxazoline hybridized lignan compound in the preparation of insecticides according to claim 1, characterized in that: The insecticide is applied to diamondback moth and oriental armyworm.

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