Capsaicin ester derivatives, methods of making and uses thereof

Abstract

This invention relates to capsaicin ester derivatives, their preparation methods, and their applications. The general structural formula of this series of capsaicin ester derivatives is shown in formula (I), where R is selected from alkyl, substituted or unsubstituted phenyl, or unsubstituted cinnamyl. Experiments have demonstrated that some compounds in this series of capsaicin ester derivatives exhibit insecticidal activity against armyworms comparable to, or even exceeding, that of the commercially available plant-derived pesticide, azadirachtin; some derivatives also show good acaricidal activity against Tetranychus cinnabarinus, with significantly improved activity compared to the parent capsaicin. Therefore, they hold promise for the preparation of highly efficient, environmentally friendly, and low-toxicity plant-derived insecticides / acaricides.

Description

Technical Field

[0001] This invention relates to capsaicin ester derivatives and the application of this series of derivatives in the preparation of plant-derived insecticides / miticides. Background Technology

[0002] Capsaicin, also known as nonivamide (structure V below), is naturally found in peppers of the Solanaceae family.

[0003]

[0004] Studies have found that capsaicin (nonivamide) consists of a benzene ring and a long hydrophobic lipid tail with a polar amide group.

[0005] [Journal of Natural Products, 1996, 59, 425-426; Comprehensive Reviews in Food Science and Food Safety, 2020, 19, 2972-2993; Journal of Medicinal Chemistry, 2022, 65, 16754-16773]. As direct structural analogs of capsaicin, they differ only slightly in structure from fatty acid side chains and have similar pharmacological effects. Furthermore, capsaicin, also known as synthetic capsaicin, is cost-effective and has potential for further development compared to other capsaicin analogs, exhibiting higher hydrophilicity. It possesses the ability to induce cell cycle arrest and oxidative stress, thereby inhibiting the growth of human corneal epithelial cells and exhibiting anticancer activity [Molecular Nutrition & Food Research, 2016, 61, 1600474; Free Radical Biology and Medicine, 2018, 120, 147-159; Toxicology, 2023, 500, 153674; Phytotherapy Research, 2019, 33, 1815-1826]. It can also be used to treat chronic pruritus. Furthermore, capsaicin and its derivatives also possess antibacterial, anti-obesity, and analgesic activities [Journal of Biochemical and Molecular Toxicology, 2023, 37, e23279; Journal of Cellular Biochemistry, 2015, 116, 1153-1163]. In addition, capsaicin is used as an antifouling agent and film-forming agent for ships [RSC Advances, 2023, 13, 17628-17632; Environmental Toxicology and Chemistry, 2013, 32, 802-809]. Notably, studies have shown that capsaicin derivatives containing sulfonate fragments exhibit significant insecticidal activity [Frontiers in Chemistry, 2022, 10, 929050]. Summary of the Invention

[0006] One of the objectives of this invention is to provide a class of capsaicin ester derivatives.

[0007] Therefore, the chemical structural formula of the capsaicin ester derivative provided by the present invention is shown in formula (I):

[0008]

[0009] Wherein: R is selected from alkyl, substituted or unsubstituted phenyl, and unsubstituted cinnamyl.

[0010] Optionally, R in the structure shown in formula (I) is selected from one of the following structures: (1) R = unsubstituted phenyl; (2) R = o-fluorophenyl; (3) R = m-fluorophenyl; (4) R = p-fluorophenyl; (5) R = o-chlorophenyl; (6) R = m-chlorophenyl; (7) R = p-chlorophenyl; (8) R = o-bromophenyl; (9) R = m-bromophenyl; (10) R = p-bromophenyl; (11) R = o-cyanophenyl; (12) R = o-nitrophenyl; (13) R = m-nitrophenyl; (14) R = p-nitrophenyl; (15) R = 16-nitrophenyl; (16) R = 17-nitrophenyl; (18) R = 19-nitrophenyl; (19) R = 19-nitrophenyl; (19) R = 19-nitrophenyl; (10) R = 19-nitrophenyl; (11) R = o-cyanophenyl; (12) R = o-nitrophenyl; (13) R = m-nitrophenyl; (14) R = p-nitrophenyl; (15) R = 19-nitrophenyl; (16) R = 19-nitrophenyl; (19 ... 5) R = o-trifluoromethylphenyl; (16) R = o-methylphenyl; (17) R = m-methylphenyl; (18) R = p-methylphenyl; (19) R = p-ethylphenyl; (20) R = o-methoxyphenyl; (21) R = m-methoxyphenyl; (22) R = p-methoxyphenyl; (23) R = unsubstituted cinnamyl; (24) R = -CH3; (25) R = -CH2CH3; (26) R = -(CH2)2CH3; (27) R = -(CH2)4CH3; (28) R =

[0011] -(CH2)6CH3; (29)R=-(CH2)7CH3; (30)R=-(CH2)8CH3; (31)R=-(CH2)9CH3; (32)R=

[0012] -(CH2) 10 CH3; (33)R=-(CH2) 11 CH3; (34)R=-(CH2) 12 CH3; (35)R=-(CH2) 14 CH3; (36)R=-(CH2) 16 CH3.

[0013] The present invention also provides a method for preparing the above-mentioned capsaicin ester compounds, the method comprising:

[0014] Step 1: Capsaicin reacts with 1-bromo-3-methyl-2-butene to prepare intermediate b, the structural formula of which is shown in Formula (II):

[0015]

[0016] Step 2: Intermediate b reacts with tin dioxide to obtain intermediate c, the structural formula of which is shown in formula (Ⅲ):

[0017]

[0018] Step 3: Intermediate c is reduced to obtain intermediate d, the structural formula of which is shown in formula (Ⅳ):

[0019]

[0020] Step 4: Intermediate d reacts with RCOOH to prepare the compound shown in formula (Ⅰ), wherein R is selected from alkyl, substituted or unsubstituted phenyl, or unsubstituted cinnamyl.

[0021] Optionally, step 2 is carried out in dimethyl sulfoxide solution at a temperature of 100-110°C for 20-30 min. Step 4 is carried out in anhydrous dichloromethane with the addition of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) at a temperature of 20-30°C. The RCOOH is selected from one of the following: acetic acid, propionic acid, butyric acid, hexanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, benzoic acid, o-fluorobenzoic acid, m-fluorobenzoic acid, p-fluorobenzoic acid, o-chlorobenzoic acid, m-chlorobenzoic acid, p-chlorobenzoic acid, o-bromobenzoic acid, m-bromobenzoic acid, p-bromobenzoic acid, p-cyanobenzoic acid, o-nitrobenzoic acid, m-nitrobenzoic acid, p-nitrobenzoic acid, m-trifluoromethylbenzoic acid, o-methylbenzoic acid, m-methylbenzoic acid, p-methylbenzoic acid, p-ethylbenzoic acid, o-methoxybenzoic acid, m-methoxybenzoic acid, p-methoxybenzoic acid, and cinnamic acid.

[0022] The capsaicin ester derivatives of the present invention are used in the preparation of insecticides. Furthermore, the capsaicin ester derivatives of the present invention are used in the preparation of acaricides. The insecticides target common agricultural lepidopteran pests, such as armyworms and diamondback moths. The mites refer to common agricultural mites, such as the carmine spider mite and the two-spotted spider mite. Attached Figure Description

[0023] Figure 1 The image shows the proton NMR spectrum of intermediate b.

[0024] Figure 2 The image shows the proton NMR spectrum of intermediate c.

[0025] Figure 3 The image shows the proton NMR spectrum of intermediate d.

[0026] Figure 4 The image shows the proton NMR spectrum of compound 1. Detailed Implementation

[0027] Unless otherwise specified, the terminology used in this document is intended for understanding by those skilled in the art.

[0028] An example of the synthetic route for the capsaicin ester derivatives described in this invention is as follows:

[0029]

[0030] Referring to the above synthetic route, the synthetic method of the compound of the present invention is exemplified as follows:

[0031] First, an appropriate amount of capsaicin (a) and potassium carbonate are dissolved in a suitable solvent (such as acetone), and then 1-bromo-3-methyl-2-butene is added. Under suitable conditions (such as 60-80℃, 9-12h), intermediate b is obtained.

[0032] Subsequently, an appropriate amount of intermediate b and tin dioxide were dissolved in a suitable solvent (such as dimethyl sulfoxide) and prepared under suitable conditions (such as 100-110℃, 20-30min) to obtain intermediate c.

[0033] Next, an appropriate amount of intermediate c and sodium borohydride are dissolved in a suitable solvent (such as methanol) and reduced under suitable conditions (such as 0°C, 30-40 min) to obtain intermediate d.

[0034] Finally, an appropriate amount of intermediate d was reacted with organic acid RCOOH in a suitable system (such as a reaction system containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 4-dimethylaminopyridine (DMAP) and anhydrous dichloromethane) and under suitable reaction conditions (such as a reaction temperature of 20-30°C) to prepare compounds 1-36 of the present invention.

[0035] The following are specific embodiments of the present invention, which will be used to further explain and illustrate the present invention in detail.

[0036] Example 1: Preparation of capsaicin ester derivative compounds 1-36

[0037] (1) Preparation of intermediate b:

[0038] 6.82 mmol capsaicin (a) and 13.64 mmol anhydrous potassium carbonate were dissolved in 30 mL acetone, followed by the addition of 10.23 mmol 1-bromo-3-methyl-2-butene. The mixture was refluxed for 12 h and detected by TLC. After the reaction was complete, the acetone was removed, and ethyl acetate (20 mL × 3) was added. The organic phases were combined, dried, concentrated, and separated by column chromatography to give intermediate b in 79% yield.

[0039] (2) Preparation of intermediate c:

[0040] 2.76 mmol of intermediate b was dissolved in 10 mL of dimethyl sulfoxide, followed by the addition of 8.28 mmol of selenium dioxide. The mixture was refluxed at 100 °C for 20–30 min, and the reaction was monitored by TLC. After the reaction was complete, water was added to quench the reaction, and ethyl acetate (20 mL × 3) was added. The organic phases were combined, dried, concentrated, and separated by column chromatography to give intermediate c in 71% yield.

[0041] (3) Preparation of intermediate d:

[0042] 2.66 mmol of intermediate c was dissolved in 15 mL of methanol and then placed in an ice bath (0 °C). 7.99 mmol of sodium borohydride was added, and the reaction was allowed to proceed for 30–40 min. TLC analysis showed that after the reaction was complete, water was added to quench the reaction, followed by the addition of ethyl acetate (20 mL × 3). The organic phases were combined, dried, concentrated, and separated by column chromatography to give intermediate d in 84% yield.

[0043] Preparation method of compounds 1-36:

[0044] Intermediate d (1 mmol), the corresponding acid (2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 2 mmol) and 4-dimethylaminopyridine (DMAP, 0.2 mmol) were weighed into 5 mL of anhydrous dichloromethane and stirred at room temperature for 16 h. After the reaction was complete, 30 mL of ethyl acetate was added for dilution, followed by washing with 0.1 M hydrochloric acid aqueous solution, 5% sodium bicarbonate aqueous solution and saturated brine. The organic phase was dried and concentrated, and compound 1-36 was separated by thin-layer chromatography (yield 19-94%).

[0045] The compounds 1-36 prepared by the above method have the following general formulas, and each corresponds to a compound having a structure of 1-36:

[0046]

[0047] Wherein: R is selected from: (1): R = unsubstituted phenyl; (2): R = o-fluorophenyl; (3): R = m-fluorophenyl; (4): R = p-fluorophenyl; (5): R = o-chlorophenyl; (6): R = m-chlorophenyl; (7): R = p-chlorophenyl; (8): R = o-bromophenyl; (9): R = m-bromophenyl; (10): R = p-bromophenyl; (11): R = o-cyanophenyl; (12): R = o-nitrophenyl; (13): R = m-nitrophenyl; (14): R = p-nitrophenyl; (15): R = o-trifluoromethylphenyl; (16): R = o-methylphenyl; (17): R = m-methylphenyl; (18): R = p-methylphenyl; (19):R = p-ethylphenyl; (20):R = o-methoxyphenyl; (21):R = m-methoxyphenyl; (22):R = p-methoxyphenyl; (23):R = unsubstituted cinnamyl; (24):R = -CH3; (25):R = -CH2CH3; (26):R = -(CH2)2CH3; (27):R = -(CH2)4CH3; (28):R = -(CH2)6CH3; (29):R = -(CH2)7CH3; (30):R = -(CH2)8CH3; (31):R = -(CH2)9CH3; (32):R = -(CH2) 10 CH3;(33):R=-(CH2) 11 CH3;(34):R=-(CH2) 12 CH3;(35):R=-(CH2) 14 CH3;(36):R=-(CH2) 16 CH3.

[0048] The physicochemical properties and identification data of the prepared compounds are as follows:

[0049] The physicochemical properties and identification data of intermediate b are as follows:

[0050] 1) White solid, yield 78%

[0051] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0052] IR cm -1 (KBr):3297,3097,2952,2851,1738,1549,1513,1471,1356,1256,1222,1133,1068,1003,859; 1H NMR (400MHz, CDCl3) δ: 6.76-6.83 (m, 3H, Ph-H), 5.76 (d, J = 17.6Hz, 1H, -NH-), 5.48-5 .52(m,1H,=CH-),4.57(d,J=6.4Hz,2H,-CH2-),4.35-4.37(m,2H,-CH2-),3.84-3.85 (m,3H,-OCH3),2.17-2.21(m,2H,-CH2-),1.76(s,3H,-CH3),1.72(s,3H,-CH3),1.61 -1.68(m,2H,-CH2-),1.25-1.31(m,10H),0.84-0.89(m,3H,-CH3); HRMS[ESI]:calcd for C 22 H 35 NO3Na([M+Na)) + ),384.2510; found,384.2516.

[0053] The physicochemical properties and identification data of intermediate C are as follows:

[0054] 1) White solid, yield 71%

[0055] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0056] IR cm -1 (KBr):3068,3019,2924,2852,2410,2348,1697,1637,1544,1518,1467,1422,1262,1235,1143,1025,1119,848,828,800; 1 H NMR(400Hz, CDCl3)δ:9.45-9.46(m,1H,-CHO),6.86(t,J=1.2Hz,1H,Ph-H),6.79-6.80(m,2 H,Ph-H),6.69-6.73(m,1H,=CH-),5.76(s,1H,-NH-),4.90-4.93(m,2H,-CH2-),4.37-4.39 (m,2H,-CH2-),3.86-3.88(m,3H,-OCH3),2.18-2.23(m,2H,-CH2-),1.81-1.82(m,3H,-CH3 ),1.61-1.68(m,2H,-CH2-),1.24-1.30(m,10H),0.84-0.88(m,3H,-CH3); HRMS[ESI]:calcd for C 22 H33 NO4Na([M+Na)) + ),398.2302; found,398.1791.

[0057] The physicochemical properties and identification data of intermediate d are as follows:

[0058] 1) White solid, yield 84%

[0059] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0060] IR cm -1 (KBr):3307,3186,2924,2852,2348,1697,1637,1594,1544,1518,1467,1422,1380,1341,1235,1119,1025,848; 1 H NMR (400MHz, CDCl3) δ: 6.76-6.82 (m, 3H, Ph-H), 5.77-5.80 (m, 1H, = CH-), 5.71-5.76 (m, 1H,-NH-),4.65(d,J=6.4Hz,2H,-CH2-),4.35-4.37(m,2H,-CH2-),4.06(d,J=2.4Hz,2H ,-CH2-),3.85(t,J=2.4Hz,3H,-OCH3),2.17-2.22(m,2H,-CH2-),1.75(s,3H,-CH3),1. 60-1.68(m,2H,-CH2-),1.25-1.32(m,10H),0.85-0.89(m,3H,-CH3); HRMS[ESI]:calcd for C 22 H 35 NO4H([M+H)) + ),378.2639; found,378.2637.

[0061] The physicochemical properties and identification data of compound 1 are as follows:

[0062] 1) White solid, yield 46%

[0063] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0064] IR cm -1 (KBr):3062,3000,2921,2852,2278,1713,1688,1637,1590,1548,1516,1460,1314,1279,1233,1121,1051,850;1 H NMR(400MHz, CDCl3)δ:8.04-8.07(m,2H,Ph-H),7.55-7.59(m,1H,Ph-H),7.43-7.46(m,2H,Ph-H),6.77- 6.84(m,3H,Ph-H),5.88-5.93(m,1H,=CH-),5.72(s,1H,-NH-),4.76(s,2H,-CH2-),4.68(d,J=6.0Hz,2H ,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),1.83(d,J=1.2 Hz,3H,-CH3),1.61-1.68(m,2H,-CH2-),1.25-1.29(m,10H),0.85-0.88(m,3H,-CH3); HRMS[ESI]:calcd for C 29 H 39 NO5H([M+H)) + ),482.2901; found,482.2901.

[0065] The physicochemical properties and identification data of compound 2 are as follows:

[0066] 1) White solid, yield 94%

[0067] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0068] IR cm -1 (KBr):3285,3095,2394,1716,1640,1558,1364,1300,1263,1232,943,805,755,639; 1H NMR(400MHz, CDCl3)δ:7.92-7.97(m,1H,Ph-H),7.49-7.56(m,1H,Ph-H),7.18-7.23(m,1H,Ph-H),7.11-7.16 (m,1H,Ph-H),6.77-6.84(m,3H,Ph-H),5.90-5.93(m,1H,=CH-),5.66(s,1H,-NH-),4.77(s,2H,-CH2-),4.68( d,J=6.0Hz,2H,-CH2-),4.36-4.38(m,2H,-CH2-),3.85(d,J=3.2Hz,3H,-OCH3),2.17-2.22(m,2H,-CH2-),1. 83(s,3H,-CH3),1.61-1.67(m,2H,-CH2-),1.25-1.31(m,10H),0.85-0.89(m,3H,-CH3); HRMS[ESI]:calcdfor C 29 H 38 FNO5H([M+H)) + ),500.2807; found,500.2177.

[0069] The physicochemical properties and identification data of compound 3 are as follows:

[0070] 1) White solid, yield 79%

[0071] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0072] IR cm -1(KBr):3286,3076,2856,2347,1714,1635,1590,1488,1423,1293,1266,1206,1139,1019,852,795,752,634; 1H NMR(400MHz, CDCl3)δ:7.83-7.86(m,1H,Ph-H),7.70-7.74(m,1H,Ph-H),7.40-7.45(m,1H,Ph-H),7.26-7.30 (m,1H,Ph-H),6.78-6.84(m,3H,Ph-H),5.88-5.92(m,1H,=CH-),5.71(s,1H,-NH-),4.76(s,2H,-CH2-),4.68 (d,J=6.4Hz,2H,-CH2-),4.38(d,J=5.6Hz,2H,-CH2-),3.86(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),1.8 3(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.32(m,10H),0.88(t,J=6.8Hz,3H,-CH3); HRMS[ESI]:calcd for C 29 H 38 FNO5H([M+H)) + ),500.2807; found,500.2796.

[0073] The physicochemical properties and identification data of compound 4 are as follows:

[0074] 1) White solid, yield 67%

[0075] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0076] IR cm -1 (KBr):3281,3068,2347,1716,1636,1517,1286,1233,1124,1025,857,798,709,634; 1H NMR(400MHz, CDCl3)δ:8.04-8.09(m,2H,Ph-H),7.09-7.14(m,2H,Ph-H),6.78-6.84(m,3H,Ph-H ),5.88-5.92(m,1H,=CH-),5.74(s,1H,-NH-),4.75(d,J=1.2Hz,2H,-CH2-),4.67(d,J=6.4Hz,2 H,-CH2-),4.38(d,J=5.6Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),1.83 (d,J=1.6Hz,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.23-1.30(m,10H),0.85-0.88(m,3H,-CH3).

[0077] The physicochemical properties and identification of compound 5 are as follows:

[0078] 1) White solid, yield 53%

[0079] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0080] 1H NMR (400MHz, CDCl3) δ: 7.85 (dd, J=1.6, 8.0Hz, 1H, Ph-H), 7.40-7.47 (m, 2H, Ph-H), 7.30-7.34 (m, 1H, Ph-H), 6 .77-6.83(m,3H,Ph-H),5.89-5.93(m,1H,=CH-),5.74(s,1H,-NH-),4.77(d,J=1.2Hz,2H,-CH2-),4.68(d,J=6 .0Hz,2H,-CH2-),4.38(d,J=5.6Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),1,85(d,J=1 .6Hz,3H,-CH3),1.61-1.68(m,2H,-CH2-),1.25-1.31(m,10H),0.88(t,J=6.4Hz,3H,-CH3); HRMS[ESI]:calcd for C 29 H 38 ClNO5H([M+H))+ ),516.2512; found,516.2514.

[0081] The physicochemical properties and identification data of compound 6 are as follows:

[0082] 1) White solid, yield 72%

[0083] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0084] IR cm -1 (KBr):3287,3072,2394,1721,1640,1564,1518,1262,1234,1142,1038,948,898,856,806,743; 1 H NMR(400MHz, CDCl3)δ:8.01-8.02(m,1H,Ph-H),7.92-7.95(m,1H,Ph-H),7.52-7.56(m,1H,Ph-H),7.37-7. 41(m,1H,Ph-H),6.77-6.84(m,3H,Ph-H),5.91(t,J=6.8Hz,1H,=CH-),5.75(s,1H,-NH-),4.76(s,2H,-CH2 -),4.67(d,J=6.4Hz,2H,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.86(d,J=2.8Hz,3H,-OCH3),2.22(t,J=7. 6Hz,2H,-CH2-),1.83(s,3H,-CH3),1.61-1.68(m,2H,-CH2-),1.25-1.33(m,10H),0.85-0.88(m,3H,-CH3).

[0085] The physicochemical properties and identification data of compound 7 are as follows:

[0086] 1) White solid, yield 19%

[0087] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0088] IR cm -1 (KBr):3299,3076,2921,2850,2361,1736,1641,1548,1513,1257,1158,1069,1009,856; 1H NMR(400MHz, CDCl3)δ:7.97-8.00(m,2H,Ph-H),7.40-7.43(m,2H,Ph-H),6.77-6.83(m,3H, Ph-H),5.87-5.91(m,1H,=CH-),5.70(s,1H,-NH-),4.75(s,2H,-CH2-),4.67(d,J=6.4Hz,2H ,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),1. 82(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.31(m,10H),0.88(t,J=6.4Hz,3H,-CH3).

[0089] The physicochemical properties and identification data of compound 8 are as follows:

[0090] 1) White solid, yield 47%

[0091] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0092] IR cm -1 (KBr):3286,3093,2919,2394,1710,1641,1562,1517,1291,1234,1126,1020,937,859,804,740; 1 H NMR (400MHz, CDCl3) δ: 7.81 (dd, J=2.0, 7.2Hz, 1H, Ph-H), 7.67 (dd, J=2.0, 7.6Hz, 1H, Ph-H), 7.31-7.39 (m,2H,Ph-H),6.77-6.83(m,3H,Ph-H),5.93(t,J=6.0Hz,1H,=CH-),5.71(s,1H,-NH-),4.77(s,2H,-CH2 -),4.68(d,J=6.4Hz,2H,-CH2-),4.38(d,J=4.4Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H ,-CH2-),1.85(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.30(m,10H),0.88(t,J=6.0Hz,3H,-CH3).

[0093] The physicochemical properties and identification data of compound 9 are as follows:

[0094] 1) White solid, yield 71%

[0095] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0096] IR cm -1 (KBr):3285,3091,2951,2919,2848,2362,2335,1721,1641,1563,1516,1469,1339,1257,1233,1119,1016,948,859,742; 1 H NMR(400MHz, CDCl3)δ:8.16-8.18(m,1H,Ph-H),7.96-7.99(m,1H,Ph-H),7.67-7.71(m,1H,Ph-H),7.30-7.35 (m,1H,Ph-H),6.78-6.84(m,3H,Ph-H),5.91(t,J=6.8Hz,1H,=CH-),5.73(d,J=30.4Hz,1H,-NH-),4.76(d,J=3 .2Hz,2H,-CH2-),4.67(d,J=5.6Hz,2H,-CH2-),4.38(t,J=4.4Hz,2H,-CH2-),3.86(d,J=4.0Hz,3H,-OCH3),2 .18-2.22(m,2H,-CH2-),1.83(s,3H,-CH3),1.65(s,2H,-CH2-),1.25-1.31(m,10H),0.84-0.89(m,3H,-CH3).

[0097] The physicochemical properties and identification data of compound 10 are as follows:

[0098] 1) White solid, yield 69%

[0099] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0100] IR cm -1 (KBr):2921,2852,2348,1717,1613,1590,1541,1464,1421,1287,1261,1226,1130,1008,849,803,754,632; 1H NMR(400MHz, CDCl3)δ:7.89-7.93(m,2H,Ph-H),7.57-7.60(m,2H,Ph-H),6.77-6.83(m,3H,Ph -H),5.88-5.91(m,1H,=CH-)5.67(s,1H,-NH-),4.75(s,2H,-CH2-),4.67(d,J=6.4Hz,2H,-CH2 -),4.38(d,J=5.6Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),1.82(d,J =1.6Hz,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.24-1.31(m,10H),0.88(t,J=6.4Hz,3H,-CH3).

[0101] The physicochemical properties and identification data of compound 11 are as follows:

[0102] 1) White solid, yield 50%

[0103] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0104] IR cm -1 (KBr):3286,3096,2347,1723,1640,1518,1271,1235,1114,1018,947,863,766,631; 1 H NMR (400MHz, CDCl3) δ: 8.16 (d, J = 8.4Hz, 2H, Ph-H), 7.77 (d, J = 8.0Hz, 2H, Ph-H), 6.78-6.84 (m, 3H,Ph-H),5.93(t,J=6.0Hz,1H,=CH-),5.72(t,J=6.0Hz,1H,-NH-),4.79(s,2H,-CH2-),4.67( d,J=6.0Hz,2H,-CH2-),4.38(d,J=5.6Hz,2H,-CH2-),3.86(s,3H,-OCH3),2.22(t,J=7.6Hz,2H ,-CH2-),1.84(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.29(m,10H),0.88(m,3H,-CH3).

[0105] The physicochemical properties and identification data of compound 12 are as follows:

[0106] 1) White solid, yield 45%

[0107] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0108] IR cm -1 (KBr):3291,3090,2847,2361,1722,1525,1358,1293,1232,1129,1069,1017,941,858; 1 H NMR(400MHz, CDCl3)δ:7.92(d,J=8.0Hz,1H),7.76(dd,J=1.6,7.2Hz,1H,Ph-H),7.62-7.70(m,2 H,Ph-H),6.77-6.82(m,3H,Ph-H),5.88(t,J=6.4Hz,1H,=CH-),5.69(s,1H,-NH-),4.75(s,2H,-C H2-),4.66(d,J=6.4Hz,2H,-CH2-),4.37(d,J=5.2Hz,2H,-CH2-),3.84(s,3H,-OCH3),2.22(t,J= 7.6Hz,2H,-CH2-),1.79(s,3H,-CH3),1.61-1.68(m,2H),1.25-1.30(m,10H),0.88(m,3H,-CH3).

[0109] The physicochemical properties and identification data of compound 13 are as follows:

[0110] 1) White solid, yield 71%

[0111] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0112] IR cm -1 (KBr):3286,3091,2347,1720,1640,1562,1526,1350,1265,1235,1138,949,718; 1H NMR (400MHz, CDCl3) δ: 8.86 (t, J = 2.0Hz, 1H, Ph-H), 8.42-8.45 (m, 1H, Ph-H), 8.37-8.40 (m, 1H, Ph-H), 7.6 5-7.69(m,1H,Ph-H),6.81-6.83(m,3H,Ph-H),5.90-5.94(m,1H,=CH-),5.78(s,1H,-NH-),4.82(s,2H,-C H2-),4.69(d,J=6.0Hz,2H,-CH2-),4.39(d,J=5.6Hz,2H,-CH2-),3.86(s,3H,-OCH3),2.23(t,J=7.6Hz,2 H,-CH2-),1.86(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.32(m,10H),0.88(t,J=6.4Hz,3H,-CH3).

[0113] The physicochemical properties and identification data of compound 14 are as follows:

[0114] 1) White solid, yield 45%

[0115] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0116] IR cm -1 (KBr):3288,3101,2394,1721,1528,1466,1286,1125,1011,848,717,624; 1 HNMR(400MHz, CDCl3)δ:8.28-8.32(m,2H,Ph-H),8.21-8.24(m,2H,Ph-H),6.78-6.84(m,3H,P h-H), 5.90-5.95 (m, 1H, = CH-), 5.73 (s, 1H, -NH-), 4.81 (d, J = 1.2Hz, 2H, -CH2-), 4.68 (d, J = 6. 0Hz,2H,-CH2-),4.39(d,J=5.6Hz,2H,-CH2-),3.86(s,3H,-OCH3),2.23(t,J=7.2Hz,2H,-CH2 -),1.85(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.24-1.30(m,10H),0.85-0.88(m,3H,-CH3).

[0117] The physicochemical properties and identification data of compound 15 are as follows:

[0118] 1) White solid, yield 73%

[0119] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0120] IR cm -1 (KBr):3287,3091,2951,2848,2360,1725,1642,1560,1517,1256,1119,1069,1017,857; 1 H NMR (400MHz, CDCl3) δ: 8.30 (s, 1H, Ph-H), 8.25 (d, J=7.6Hz, 1H, Ph-H), 7.83 (d, J=7.6Hz, 1H, Ph-H), 7.61 ( t,J=8.0Hz,1H,Ph-H),6.77-6.84(m,3H,Ph-H),5.89-5.93(m,1H,=CH-),5.70(s,1H,-NH-),4.80(s,2H,- CH2-),4.68(d,J=6.0Hz,2H,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.22(t,J=7.6Hz, 2H,-CH2-),1.84(s,3H,-CH3),1.61-1.67(m,2H,-CH2-),1.26-1.29(m,10H),0.88(t,J=6.4Hz,3H,-CH3).

[0121] The physicochemical properties and identification data of compound 16 are as follows:

[0122] 1) White solid, yield 71%

[0123] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0124] IR cm -1(KBr):3290,3094,2348,1715,1558,1516,1293,1260,1139,1080,1012,946,857,803,734,650; 1H NMR (400MHz, CDCl3) δ: 7.94 (dd, J = 1.6, 8.4Hz, 1H, Ph-H), 7.38-7.42 (m, 1H, Ph-H), 7.22-7.24 (m, 2H, Ph-H), 6. 77-7.84(m,3H,Ph-H),5.91(t,J=6.4Hz,1H,=CH-),5.69(s,1H,-NH-),4.73(s,2H,-CH2-),4.68(d,J=6.4Hz,2H ,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.60(s,3H,-CH3),2.22(t,J=7.6Hz,2H,-CH2-),1 .84(s,3H,-CH3),1.61-1.68(m,2H,-CH2-),1.25-1.33(m,10H),0.88(t,J=6.4Hz,3H,-CH3); HRMS[ESI]:calcd for C 30 H 41 NO5H([M+H)) + ),496.3058; found,496.3657.

[0125] The physicochemical properties and identification data of compound 17 are as follows:

[0126] 1) White solid, yield 78%

[0127] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0128] IR cm -1 (KBr):3283,3090,2951,2847,1711,1641,1560,1516,1425,1290,1124,1069,1018,857; 1H NMR(400MHz, CDCl3)δ:7.84-7.86(m,2H,Ph-H),7.38(d,J=7.6Hz,1H,Ph-H),7.34(t,J=7.6Hz,1H,Ph-H), 6.77-6.84(m,3H,Ph-H),5.88-5.92(m,1H,=CH-)5.66(s,1H,-NH-),4.75(s,2H,-CH2-),4.68(d,J=6.4Hz, 2H,-CH2-),4.38(dd,J=2.0,5.6Hz,2H,-CH2-),3.85(d,J=2.0Hz,3H,-OCH3),2.40(s,3H,-CH3),2.22(t, J=7.6Hz,2H,-CH2-),1.83(s,3H,-CH3),1.61-1.68(m,2H,-CH2-),1.25-1.31(m,10H),0.88(m,3H,-CH3).

[0129] The physicochemical properties and identification data of compound 18 are as follows:

[0130] 1) White solid, yield 78%

[0131] 2) Infrared spectrum, nuclear magnetic resonance spectrum, and high-resolution mass spectrometry characteristics of this compound:

[0132] IR cm -1 (KBr):3296,3066,2923,2394,1718,1640,1514,1464,1374,1285,1130,1001,849,801,750,632; 1 H NMR (400MHz, CDCl3) δ: 7.93-7.95 (m, 2H, Ph-H), 7.25 (d, J = 8.0Hz, 2H, Ph-H), 6.77-6.84 (m, 3H, Ph-H ),5.88-5.92(m,1H,=CH-),5.72(s,1H,-NH-),4.74(s,2H,-CH2-),4.67(d,J=6.0Hz,2H,-CH2-),4. 38(d,J=5.2Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.41(s,3H,-CH3),2.22(t,J=7.6Hz,2H,-CH2-),1. 83(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.29(m,10H),0.88(m,3H,-CH3); HRMS[ESI]:calcd for C 30 H 41NO5H([M+H)) + ),496.3058; found,496.3076.

[0133] The physicochemical properties and identification data of compound 19 are as follows:

[0134] 1) White solid, yield 83%

[0135] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0136] IR cm -1 (KBr):3292,3089,2957,2918,2918,2864,2279,1720,1641,1561,1517,1271,1235,1109,999,949,851,805,722,653; 1 H NMR (400MHz, CDCl3) δ: 7.96-7.98 (m, 2H, Ph-H), 7.28 (d, J = 8.4Hz, 2H, Ph-H), 6.77-6.84 (m, 3H, Ph-H ),5.88-5.92(m,1H,=CH-),5.71(s,1H,-NH-),4.75(s,2H,-CH2-),4.67(d,J=6.4Hz,2H,-CH2-),4. 38(d,J=5.2Hz,2H,-CH2-),3.85(s,3H,-OCH3),2.73(dd,J=7.6,15.2Hz,2H,-CH2-),2.22(t,J=7.6 Hz,2H,-CH2-),1,83(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.24-1.33(m,13H),0.88(m,3H,-CH3).

[0137] The physicochemical properties and identification data of compound 20 are as follows:

[0138] 1) White solid, yield 48%

[0139] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0140] IR cm -1 (KBr):3286,3096,2394,1731,1639,1543,1515,1309,1256,1233,1134,1022,855,800,753,627; 1H NMR(400MHz, CDCl3)δ:7.80-7.83(m,1H,Ph-H),7.45-7.50(m,1H,Ph-H),6.96-7.00(m,2H,Ph-H),6.77-6.8 3(m,3H,Ph-H),5.89-5.93(m,1H,=CH-),5.71(s,1H,-NH-),4.73(s,2H,-CH2-),4.68(d,J=6.0Hz,2H,-CH2- ),4.38(d,J=6.4Hz,2H,-CH2-),3.89(d,J=1.6Hz,3H,-OCH3),3.85(d,J=2.0Hz,3H,-OCH3),2.22(t,J=7.6H z,2H,-CH2-),1.83(s,3H,-CH3),1.61-1.67(m,2H,-CH2-),1.25-1.30(m,10H),0.88(t,J=6.0Hz,3H,-CH3);

[0141] The physicochemical properties and identification data of compound 21 are as follows:

[0142] 1) White solid, yield 87%

[0143] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0144] IR cm -1 (KBr):33291,3094,2956,2348,1719,1641,1560,1518,1466,1319,1276,1202,1105,1033,954,859,807,753,720; 1H NMR(400MHz, CDCl3)δ:7.64-7.66(m,1H,Ph-H),7.57(dd,J=1.6,2.8Hz,1H,Ph-H),7.37(d,J=8.0Hz,1H,Ph-H) ,7.09-7.12(m,1H,Ph-H),6.77-6.84(m,3H,Ph-H),5.88-5.92(m,1H,=CH-),5.73(s,1H,-NH-),4.76(s,2H,-C H2-),4.67(d,J=6.0Hz,2H,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85(s,6H),2.22(t,J=7.6Hz,2H,-CH2-),1 .83(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.31(m,10H),0.88(t,J=6.8Hz,3H,-CH3); HRMS[ESI]:calcd for C 30 H 41 NO6Na([M+Na)) + ),534.2827; found,534.2167.

[0145] The physicochemical properties and identification data of compound 22 are as follows:

[0146] 1) White solid, yield 47%

[0147] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0148] IR cm -1 (KBr):3096,2951,2849,2361,2335,1713,1646,1540,1514,1468,1285,1164,1132,1068,1003,857; 1H NMR(400MHz, CDCl3)δ:7.98-8.02(m,2H,Ph-H),6.90-6.94(m,2H,Ph-H),6.77-6.84(m,3H,Ph-H),5 .87-5.91(m,1H,=CH-),5.66(s,1H,-NH-),4.73(s,2H,-CH2-),4.67(d,J=6.4Hz,2H,-CH2-),4.36-4 .38(m,2H,-CH2-),3.86(d,J=2.0Hz,3H,-OCH3),3.85(d,J=2.4Hz,3H,-OCH3),2.22(t,J=7.6Hz,2H ,-CH2-),1.82(s,3H,-CH3),1.61-1.69(m,2H,-CH2-),1.25-1.30(m,10H),0.85-0.89(m,3H,-CH3);

[0149] The physicochemical properties and identification data of compound 23 are as follows:

[0150] 1) White solid, yield 56%

[0151] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0152] IR cm -1 (KBr):3291,3066,2394,1717,1641,1551,1515,1309,1161,1007,855,707,637; 1 H NMR(400MHz, CDCl3)δ:7.73(d,J=16.0Hz,1H,=CH-),7.51-7.54(m,2H,Ph-H),7.38-7.40(m,3H,Ph -H),6.78-6.83(m,3H,Ph-H),6.48(d,J=16.0Hz,1H,=CH-),5.88(t,J=6.0Hz,1H,=CH-),5.70(s,1 H,-NH-),4.67(d,J=7.2Hz,4H),4.38(d,J=4.4Hz,2H,-CH2-),3.86(s,3H,-OCH3),2.22(t,J=7.2H z,2H,-CH2-),1.80(s,3H,-CH3),1.65-1.68(m,2H,-CH2-),1.26-1.32(m,10H),0.88(m,3H,-CH3);

[0153] The physicochemical properties and identification data of compound 24 are as follows:

[0154] 1) White solid, yield 59%

[0155] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0156] IR cm -1 (KBr):3306,3071,2923,2852,2362,1739,1638,1545,1515,1468,1359,1231,1136,1067,1005,858; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.84 (m, 3H, Ph-H), 5.78-5.82 (m, 1H, = CH-) 5.73 (s, 1H, - NH-),4.64(d,J=6.0Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-) ,3.85(s,3H,-OCH3),2.22(t,J=7.6Hz,2H,-CH2-),2.08s,3H,-CH3),1.75(s,3H,-CH 3),1.61-1.69(m,2H,-CH2-),1.25-1.32(m,10H),0.85-0.88(t,J=6.0Hz,3H,-CH3).

[0157] The physicochemical properties and identification data of compound 25 are as follows:

[0158] 1) White solid, yield 71%

[0159] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0160] IR cm -1(KBr):3300,3073,2950,2852,2362,1740,1642,1545,1514,1467,1351,1259,1225,1181,1136,1069,1010,858,804; 1H NMR(400MHz, CDCl3)δ:6.77-6.84(m,3H,Ph-H),5.77-5.82(m,1H,=CH-),5.70(s,1H,-NH- ),4.64(d,J=6.0Hz,2H,-CH2-),4.51(s,2H,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85(s, 3H,-OCH3),2.33-2.39(m,2H,-CH2-),2.22(t,J=7.6Hz,2H,-CH2-),1.75(s,3H,-CH3),1.6 1-1.69(m,2H,-CH2-),1.25-1.32(m,10H),1.17(t,J=7.6Hz,3H,-CH3),0.88(m,3H,-CH3).

[0161] The physicochemical properties and identification data of compound 26 are as follows:

[0162] 1) White solid, yield 64%

[0163] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0164] IR cm -1 (KBr):3303,3072,2925,2852,2362,1738,1641,1548,1513,1466,1259,1225,1170,1068,1009,857; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.84 (m, 3H, Ph-H), 5.81 (t, J = 6.4Hz, 1H, = CH-), 5.73 (s, 1H, - NH-),4.64(d,J=6.4Hz,2H,-CH2-),4.51(s,2H,-CH2-),4.38(d,J=5.2Hz,2H,-CH2-),3.85 (s,3H,-OCH3),2.33(t,J=7.6Hz,2H,-CH2-),2.23(t,J=7.6Hz,2H,-CH2-),1.75(s,3H,-CH 3),1.61-1.69(m,4H),1.26-1.34(m,10H),0.97(t,J=7.2Hz,3H,-CH3),0.88(m,3H,-CH3).

[0165] The physicochemical properties and identification data of compound 27 are as follows:

[0166] 1) White solid, yield 61%

[0167] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0168] IR cm -1 (KBr):3298,3093,2952,2851,2362,1738,1643,1514,1353,1223,1161,1068,1008,859; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.82 (m, 3H, Ph-H), 5.81 (t, J = 6.4Hz, 1H, = CH-), 5.69 ( s,1H,-NH-),4.64(d,J=6.4Hz,2H,-CH2-),4.51(s,2H,-CH2-),4.38(d,J=5.6Hz,2H ,-CH2-),3.85(s,3H,-OCH3),2.34(t,J=7.2Hz,2H,-CH2-),2.23(t,J=7.6Hz,2H,-C H2-),1.75(s,3H,-CH3),1.59-1.69(m,4H),1.25-1.33(m,14H),0.85-0.91(m,6H).

[0169] The physicochemical properties and identification data of compound 28 are as follows:

[0170] 1) White solid, yield 94%

[0171] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0172] IR cm -1 (KBr):3301,2952,2851,2361,1737,1641,1548,1513,1256,1223,1160,1068,1008,859; 1H NMR (400MHz, CDCl3) δ: 6.77-6.82 (m, 3H, Ph-H), 5.81 (t, J = 6.4Hz, 1H, = CH-), 5.67 ( s,1H,-NH-),4.64(d,J=6.0Hz,2H,-CH2-),4.51(s,2H,-CH2-),4.38(d,J=4.0Hz,2 H,-CH2-),3.85(s,3H,-OCH3),2.31-2.36(m,2H,-CH2-),2.23(t,J=7.6Hz,2H,-CH 2-),1.75(s,3H,-CH3),1.60-1.67(m,4H),1.26-1.32(m,18H),0.85-0.89(m,6H).

[0173] The physicochemical properties and identification data of compound 29 are as follows:

[0174] 1) White solid, yield 34%

[0175] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0176] IR cm -1 (KBr):3298,3095,2952,2852,2362,2335,1737,1548,1514,1352,1222,1160,1068,1008,859,687; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.82 (m, 3H, Ph-H), 5.78-5.81 (m, 1H, = CH-), 5.65 (s, 1H ,-NH-),4.64(d,J=6.4Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(dd,J=2.0,5.6Hz,2 H,-CH2-),3.85(s,3H,-OCH3),2.34(t,J=7.6Hz,2H,-CH2-),2.22(t,J=8.0Hz,2H,- CH2-),1.74(s,3H,-CH3),1.60-1.67(m,4H),1.25-1.32(m,20H),0.85-0.89(m,6H).

[0177] The physicochemical properties and identification data of compound 30 are as follows:

[0178] 1) White solid, yield 66%

[0179] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0180] IR cm -1(KBr):3094,2952,2850,2362,1737,1547,1515,1435,1349,1217,1158,1068,1008,860; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.82 (m, 3H, Ph-H), 5.81 (t, J = 6.4Hz, 1H, = CH-) 5.70 (s ,1H,-NH-),4.64(d,J=6.0Hz,2H,-CH2-),4.51(s,2H,-CH2-),4.38(d,J=5.6Hz,2H ,-CH2-),3.85(s,3H,-CH3),2.34(t,J=7.6Hz,2H,-CH2-),2.22(t,J=7.6Hz,2H,-C H2-),1.75(s,3H,-CH3),1.59-1.69(m,4H),1.26-1.33(m,22H),0.85-0.89(m,6H).

[0181] The physicochemical properties and identification data of compound 31 are as follows:

[0182] 1) White solid, yield 63%

[0183] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0184] IR cm -1 (KBr):3303,3077,2922,2852,2362,1735,1549,1514,1468,1257,1223,1161,1068,1009,858,802; 1 H NMR(400MHz, CDCl3)δ:6.77-6.84(m,3H,Ph-H),5.78-5.82(m,1H,=CH-),5.69(s,1 H,-NH-),4.64(d,J=6.0Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(d,J=5.6Hz,2H,- CH2-),3.85(s,3H,-OCH3),2.34(t,J=7.6Hz,2H,-CH2-),2.22(t,J=7.6Hz,2H,-CH 2-),1.74(s,3H,-CH3),1.58-1.69(m,4H),1.25-1.31(m,24H),0.85-0.89(m,6H).

[0185] The physicochemical properties and identification data of compound 32 are as follows:

[0186] 1) White solid, yield 66%

[0187] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0188] IR cm -1 (KBr):3236,3068,2852,2394,1737,1641,1549,1513,1468,1260,1224,1159,1008,854,802,727; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.82 (m, 3H, Ph-H), 5.81 (t, J = 6.4Hz, 1H, = CH-) 5.70 (s, 1H ,-NH-),4.64(d,J=6.4Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(dd,J=2.4,5.6Hz,2H,- CH2-),3.85(d,J=1.6Hz,3H,-OCH3),2.34(t,J=7.6Hz,2H,-CH2-),2.22(t,J=7.2Hz,2H ,-CH2-),1.74(s,3H,-CH3),1.58-1.68(m,4H),1.25-1.33(m,26H),0.85-0.89(m,6H).

[0189] The physicochemical properties and identification data of compound 33 are as follows:

[0190] 1) White solid, yield 63%

[0191] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0192] IR cm -1 (KBr):3303,3073,2921,2851,2362,1734,1641,1591,1549,1513,1467,1259,1225,1161,1068,1009,857,802,728; 1H NMR(400MHz, CDCl3)δ:6.77-6.82(m,3H,Ph-H),5.78-5.82(m,1H,=CH-),5.70(s,1 H,-NH-),4.64(d,J=6.4Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(d,J=5.6Hz,2H,- CH2-),3.85(s,3H,-OCH3),2.34(d,J=7.6Hz,2H,-CH2-),2.22(t,J=7.6Hz,2H,-CH 2-),1.75(s,3H,-CH3),1.58-1.69(m,4H),1.25-1.31(m,28H),0.85-0.89(m,6H).

[0193] The physicochemical properties and identification data of compound 34 are as follows:

[0194] 1) White solid, yield 53%

[0195] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0196] IR cm -1 (KBr):3299,3067,2921,2852,2347,1737,1642,1549,1514,1469,1259,1224,1159,1008,855,802,726,641; 1 H NMR (400MHz, CDCl3) δ: 6.77-6.82 (m, 3H, Ph-H), 5.78-5.82 (m, 1H, = CH-) 5.68 (s, 1 H,-NH-),4.64(d,J=6.0Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(d,J=5.6Hz,2H,- CH2-),3.85(s,3H,-OCH3),2.34(t,J=7.2Hz,2H,-CH2-),2.22(t,J=7.6Hz,2H,-CH 2-),1.74(s,3H,-CH3),1.58-1.69(m,4H),1.25-1.32(m,30H),0.85-0.89(m,6H).

[0197] The physicochemical properties and identification data of compound 35 are as follows:

[0198] 1) White solid, yield 71%

[0199] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0200] IR cm-1 (KBr):3296,3069,2921,2348,1736,1640,1545,1469,1261,1224,1160,1008,854,802,723,642; 1 H NMR(400MHz, CDCl3)δ:6.77-6.82(m,3H),5.78-5.82(m,1H,=CH-),5.65(s,1H,- NH-),4.64(d,J=6.4Hz,2H,-CH2-),4.50(s,2H,-CH2-),4.38(d,J=5.6Hz,2H,-CH 2-),3.85(s,3H,-OCH3),2.34(t,J=7.6Hz,2H,-CH2-),2.22(t,J=7.2Hz,2H,-CH2 -),1.74(s,3H,-CH3),1.58-1.69(m,4H),1.25-1.32(m,34H),0.85-0.89(m,6H).

[0201] The physicochemical properties and identification data of compound 36 are as follows:

[0202] 1) White solid, yield 68%

[0203] 2) The infrared spectrum and nuclear magnetic resonance spectrum of this compound:

[0204] IR cm -1 (KBr):3096,2851,2362,1736,1637,1541,1469,1231,1161,1005,857,801,721; 1 H NMR(400MHz, CDCl3)δ:6.77-6.82(m,3H),5.78-5.82(m,1H,=CH-)5.66(s,1H,-N H-),4.64(d,J=6.4Hz,2H,-CH2-),4.51(s,2H,-CH2-),4.38(d,J=5.6Hz,2H,-CH2 -),3.85(s,3H,-OCH3),2.34(t,J=7.2Hz,2H,-CH2-),2.22(t,J=7.6Hz,2H,-CH2 -),1.75(s,3H,-CH3),1.58-1.69(m,4H),1.25-1.32(m,38H),0.85-0.89(m,6H).

[0205] Example 2: Bioassay of Tetranychus cinnabarinus

[0206] 1. Test insect: Tetranychus cinnabarinus Boisduval, which was subcultured and bred by the Plant Protection Laboratory of Northwest A&F University.

[0207] 2. Samples and reagents:

[0208] The samples were: 98.32% spirodiclofen technical grade (provided by Shaanxi Meibang Pesticide Co., Ltd.) (positive control), parent capsaicin (a), intermediate (bd) and compounds 1-36 prepared in Example 1, acetone (solvent, Chengdu Kelong Chemical Reagent Factory, analytical grade), Tween 80, and water.

[0209] 3. Bioassay method: The FAO-recommended slide immersion method is used.

[0210] ① Preparation of 0.1‰ Tween 80 stock solution: Weigh 25mg Tween 80 and dissolve it in 5mL of acetone solution, then dilute with distilled water to 250mL for later use.

[0211] ② Preparation of primary screening solution: Weigh 3.0 mg of the test compound, dissolve it in 120 μL of acetone (2% of the target volume), and then dilute to 6.0 mL with the prepared 0.1‰ Tween 80 solution to prepare a 500 mg / L solution for primary screening.

[0212] ③ Preparation of test mites: Attach 1cm wide double-sided tape to one end of a glass slide. Use a No. 0 brush to select healthy, active, and uniformly aged female adult spider mites (Tetranychus carmineus). Carefully and neatly attach their backs to the double-sided tape, about 35 mites per slide, arranged in 2 rows. Place the slides with the test mites in an iron tray lined with a moist sponge. Place the iron tray in a light incubator at 26±1℃, relative humidity 60%~80%, and light intensity L∶D=14h∶10h. After 4 hours, examine with a stereomicroscope, remove dead and inactive individuals, and record the number of live mites on each slide.

[0213] ④ Immersion in medication: Immerse the end of the slide with the mite in the test medication solution and shake for 5 seconds. Then remove the slide and carefully absorb the excess medication with a small filter paper strip (be careful not to touch the mite). Place the slide back in the iron tray and put it in a light incubator under the same rearing conditions. One slide is one treatment. Each treatment is repeated 3 times. Use 0.1‰ Tween 80 solution as a blank control.

[0214] ⑤ Results Statistics: After 24 hours of treatment with the drug, the slides were removed and examined under a stereomicroscope. During the examination, the mites were gently touched with the tip of a brush; those whose chelicerae did not move were considered dead, and the number of dead individuals was recorded. The observation and recording continued for 72 hours. The results are shown in Table 1.

[0215] Table 1. Acaricidal activity of capsaicin, intermediate (bd), and derivatives 1-36 of this invention.

[0216]

[0217]

[0218]

[0219] The results showed that the acaricidal activities of compounds 2, 3, 8, 16, 23, 2948h and 72h were significantly improved compared with capsaicin, and the acaricidal activity of compound 13 at 72h was significantly improved compared with capsaicin. They are expected to be used to develop and prepare efficient, environmentally friendly and low-toxic plant-derived acaricides.

[0220] Example 3: Bioassay Experiment of Oriented Armyworm

[0221] 1. Test insect: Early 3rd instar Eastern armyworm (Mythimna separata Walker), provided by the Pollution-Free Pesticide Research Center of Northwest A&F University.

[0222] 2. Samples and reagents: parent capsaicin, azadirachtin (positive control), intermediate (bd) and compounds 1-36 prepared in Example 1, acetone (solvent, Chengdu Kelong Chemical Reagent Factory, analytical grade).

[0223] 3. Biometric Testing Methods:

[0224] The small-leaved butterfly addition method (Zhang Xinghe and Zhao Shanhuan, 1983): Acetone was used as a blank control, and azadirachtin was used as a reagent control. The activity of the test compound at a concentration of 1 mg / mL was determined. A layer of filter paper was placed at the bottom of a 9 cm diameter glass petri dish, and water was added to keep it moist. Ten early third-instar larvae were picked from each dish, and three replicates were set for each treatment sample. Freshly picked oat leaves were cut into 1×1 cm pieces after removing the main veins. 2 Leaf butterflies were immersed for 3 seconds in pre-prepared test and control solutions, then air-dried before being fed to the test insects. They were reared at approximately 25°C, with humidity ranging from 35% to 80% and a light duration of 12 hours per 12 hours. After the test insects finished consuming the oat leaves, leaf butterflies containing the drug solution were added. After 48 hours of rearing, they were fed fresh leaves without the drug solution until they emerged. The amount of food consumed, the number of surviving insects, and the symptoms observed were recorded regularly. The experimental results were used to calculate the corrected mortality rate (%) of the test insects at different stages using the following formula.

[0225]

[0226] Table 2. Stomach toxicity activities of capsaicin (a), intermediates (bd) and derivatives 1-36 of this invention against *Myxocytosporum tobira*.

[0227]

[0228]

[0229] The results showed that compounds 1-36 were more effective than capsaicin in controlling the Eastern armyworm, and some capsaicin ester derivatives (3, 6, 7, 9, 13, 15-18, 20, 27, 32, 34) achieved a final mortality rate of 51.4%-65.7% against the Eastern armyworm, which was higher than that of the commercially available azadirachtin (48.6%). This indicates that the compounds of this invention have good growth and development activity against lepidopteran pests, represented by the Eastern armyworm, and therefore hold promise for use in the preparation of environmentally friendly, low-toxicity plant-derived insecticides.

Claims

1. A capsaicin ester derivative, characterized in that, Its chemical structural formula is shown in formula (I). (I) In the structure shown in equation (I), R is selected from one of the following structures: (2) R = o-fluorophenyl; (3) R = m-fluorophenyl; (6) R = m-chlorophenyl; (7) R = p-chlorophenyl; (8) R = o-bromophenyl; (9) R = m-bromophenyl; (13) R = m-nitrophenyl; (15) R = m-trifluoromethylphenyl; (16) R = o-methylphenyl; (18) R = p-methylphenyl; (20) R = o-methoxyphenyl; (23) R = unsubstituted cinnamyl; (27) R = -(CH2)4CH3; (32) R = -(CH2) 10 CH3; (34)R=-(CH2) 12 CH3.

2. The application of capsaicin ester derivatives of claim 1, wherein R is a group of (3), (6), (7), (9), (13), (15), (18), (20), (27), (32) and (34), in the preparation of insecticides.

3. The application of capsaicin ester derivatives of claim 1, wherein R is a group of (3), (6), (7), (9), (13), (15), (18), (20), (27), (32) and (34), in the preparation of insecticides for lepidopteran pests.

4. The application of capsaicin ester derivatives of claim 1, wherein R is a (2), (3), (8), (16) and (23) group, in the preparation of acaricides.

5. The method for preparing capsaicin ester compounds according to claim 1, characterized in that, The preparation method includes: Step 1: The compound shown in formula (a) reacts with 1-bromo-3-methyl-2-butene to prepare intermediate b, the intermediate b having the structural formula shown in formula (II): （a） (Ⅱ) Step 2: Intermediate b reacts with selenium dioxide to obtain intermediate c, the structural formula of which is shown in formula (Ⅲ): (III) Step 3: Intermediate c is reduced to obtain intermediate d, the structural formula of which is shown in formula (Ⅳ): (IV) Step 4: Intermediate d reacts with RCOOH to prepare the compound shown in formula (Ⅰ), wherein RCOOH is selected from one of the following: autoic acid, dodecanoic acid, tetradecanoic acid, o-fluorobenzoic acid, m-fluorobenzoic acid, m-chlorobenzoic acid, p-chlorobenzoic acid, o-bromobenzoic acid, m-bromobenzoic acid, m-nitrobenzoic acid, m-trifluoromethylbenzoic acid, o-methylbenzoic acid, p-methylbenzoic acid, o-methoxybenzoic acid, and cinnamic acid.

6. The method for preparing capsaicin ester derivatives according to claim 5, characterized in that, Step 2 is carried out in a dimethyl sulfoxide solution at a temperature of 100-110℃ for 20-30 minutes.

7. The method for preparing capsaicin ester derivatives according to claim 5, characterized in that, Step 4 is carried out in anhydrous dichloromethane, with the addition of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) at a reaction temperature of 20-30℃.

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