Capsaicin ester derivative as well as preparation method and application thereof

Abstract

The invention relates to capsaicin ester derivatives as well as a preparation method and application thereof. The structural general formula of the series of capsaicin ester derivatives is as shown in formula (I), wherein R is selected from alkyl, substituted or non-substituted phenyl and non-substituted cinnamyl. Experiments prove that the insecticidal activity of part of compounds in the capsaicin ester derivatives to armyworms is equivalent to that of commercialized botanical pesticide toosendanin, and even higher than that of toosendanin; part of the derivatives have better acaricidal activity on tetranychus cinnabarinus, and the activity is remarkably improved compared with that of parent capsaicin, so that the derivatives are expected to be used for preparing efficient, environment-friendly and low-toxicity plant source insecticides / acaricides. # imgabs0 #

Description

Technical Field

[0001] The invention relates to capsaicin ester derivatives and application of the series of capsaicin derivatives in preparing botanical insecticides / acaricides. Background Art

[0002] Capsaicin, also known as nonivamide (structurally shown in Formula V), is naturally present in peppers of the Solanaceae family.

[0003]

[0004] Studies have found that capsaicin (Nonivamide) is composed 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

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

[0007] To this end, the chemical structural formula of the capsaicin ester derivatives provided by the present invention is as 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 = o-chlorophenyl; (16) R = m-chlorophenyl; (17) R = m-chlorophenyl; (18) R = o-bromophenyl; (19) R = m-bromophenyl; (20) R = m-bromophenyl; (21) R = m-bromophenyl; (22) R = m-nitrophenyl; (23) R = m-nitrophenyl; (24) R = m-nitrophenyl; (25) R = m-nitrophenyl; (26) R = m-nitrophenyl; (27) R = m-nitrophenyl; (28) R = m-nitrophenyl; (29) R = m-nitrophenyl; (30) R = m-nitrophenyl; (31) R = m-nitrophenyl; (32) R = m-nitrophenyl; (33) R = m-nitrophenyl; (34) R = m-nitrophenyl; (35) R = m-nitrophenyl; (36) R = m-nitrophenyl; (37) R = m-nitrophenyl; (38) R = m-nitrophenyl; (39) R = m-nitrophenyl; (40) R = m-nitrophenyl; (41) R = m-nitrophenyl; (42) R = m-nitrophenyl; (43) 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 compound, the preparation method comprising:

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

[0015]

[0016] Step 2, intermediate b reacts with tin dioxide to obtain intermediate c, wherein the intermediate c has a structural formula as shown in formula (III):

[0017]

[0018] Step 3, intermediate c is subjected to reduction reaction to obtain intermediate d, wherein the intermediate d has a structural formula as shown in formula (IV):

[0019]

[0020] Step 4, the intermediate d is reacted with RCOOH to prepare a compound represented by formula (I), wherein R is selected from alkyl, substituted or unsubstituted phenyl, and unsubstituted cinnamyl.

[0021] Optionally, the reaction of step 2 is carried out in a dimethyl sulfoxide solution, the reaction temperature is 100-110° C., and the reaction time is 20-30 min. The reaction of step 4 is carried out in anhydrous dichloromethane, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) are added simultaneously, and the reaction temperature is 20-30° C. The RCOOH is selected from one of 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 for preparing insecticides. And the capsaicin ester derivatives of the present invention are used for preparing miticides. The insecticide targets pests including common lepidopteran pests in agriculture, such as common armyworms, diamondback moths, etc. The mites refer to common mites in agriculture, such as cinnabarinus spider mites, two-spotted spider mites, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the H NMR spectrum of intermediate b.

[0024] Figure 2 This is the H NMR spectrum of intermediate c.

[0025] Figure 3 This is the H NMR spectrum of intermediate d.

[0026] Figure 4 is the H NMR spectrum of compound 1. DETAILED DESCRIPTION

[0027] Unless otherwise specified, the terms used herein are understood according to those of ordinary skill in the relevant art.

[0028] The synthetic route of the capsaicin ester derivatives of the present invention is exemplified as follows:

[0029]

[0030] With reference 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° C., 9-12 h) to obtain intermediate b;

[0032] Subsequently, an appropriate amount of intermediate b and tin dioxide are dissolved in a suitable solvent (such as dimethyl sulfoxide) and suitable conditions (such as 100-110° C., 20-30 min) 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 subjected to reduction reaction under suitable conditions (such as 0°C, 30-40 min) to obtain intermediate d;

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

[0035] The following are specific embodiments of the present invention to further explain the present invention in detail.

[0036] Example 1: Preparation of Capsaicin Ester Derivative Compound 1-36

[0037] (1) Preparation of intermediate b:

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

[0039] (2) Preparation of intermediate c:

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

[0041] (3) Preparation of intermediate d:

[0042] 2.66mmol of intermediate c was dissolved in 15mL of methanol, then placed in an ice bath (0°C), 7.99mmol of sodium borohydride was added, and the reaction was continued for 30-40min. After TLC detection, water was added to quench the reaction after the reaction was complete, ethyl acetate (20mL×3) was added, the organic phases were combined, dried, concentrated, and separated by column chromatography to obtain intermediate d with a yield of 84%.

[0043] Preparation method of compound 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 in 5 mL of anhydrous dichloromethane and stirred at room temperature for 16 h; TLC detection, after the reaction was complete, 30 mL of ethyl acetate was added to dilute, and then 0.1 M hydrochloric acid aqueous solution, 5% sodium bicarbonate aqueous solution and saturated brine were added in sequence for washing, the organic phase was dried and concentrated, and compound 1-36 (yield 19-94%) was separated by thin layer chromatography.

[0045] The compounds 1-36 prepared by the above preparation method have the following general formulae, and correspond to compounds having structures of 1 to 36 respectively:

[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 phenyl; (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 spectrum characteristics of the 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 spectrum characteristics of the 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 spectrum characteristics of the 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 spectrum characteristics of the 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 spectrum characteristics of the 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 spectrum characteristics of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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 spectrum characteristics of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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 spectrum characteristics of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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 spectrum characteristics of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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) Infrared spectrum and nuclear magnetic resonance spectrum of the 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 insects: Tetranychus cinnabarinus Boisduval, which was reared by the Plant Protection Laboratory of Northwest Agriculture and Forestry University.

[0207] 2. Samples and reagents:

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

[0209] 3. Bioassay method: Use the slide immersion method recommended by FAO:

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

[0211] ② Preparation of preliminary 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 0.1‰ Tween 80 to prepare a 500 mg / L solution for preliminary screening.

[0212] ③ Preparation of test mites: stick a 1cm wide double-sided tape on one end of the slide, use a No. 0 brush to select healthy and active female adult cinnabarinus mites of the same age, carefully and neatly stick their backs on the double-sided tape, stick about 35 mites to each slide, arrange them in 2 rows, put the slide with the test mites on an iron plate padded with a moist sponge, and put the iron plate in a light incubator under the conditions of 26±1℃, relative humidity 60%~80%, and light L:D=14h:10h. After 4 hours, check with a stereo microscope, remove dead and inactive individuals, and record the number of live mites on each slide.

[0213] ④ Soak in medicine: Dip the end of the glass slide with the mite stuck on it in the test solution for 5 seconds after shaking, then take it out, carefully absorb the excess solution with a small filter paper strip (be careful not to touch the mite body), then put it back on the iron plate, and place it in a light incubator under the same breeding conditions. One glass slide is one treatment, and each treatment is repeated 3 times, with 0.1‰ Tween 80 solution as the blank control.

[0214] ⑤ Result statistics: After 24 hours of immersion treatment, the slides were taken out and examined under a stereomicroscope. During the examination, the mites were lightly 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 was 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 the present invention

[0216]

[0217]

[0218]

[0219] The results showed that the acaricidal activity of compounds 2, 3, 8, 16, 23, 29 at 48 h and 72 h was significantly improved compared with that of capsaicin, and the acaricidal activity of compound 13 at 72 h was significantly improved compared with that of capsaicin, and they are expected to be used in the development and preparation of highly efficient, environmentally friendly and low-toxic botanical acaricides.

[0220] Example 3: Oriental armyworm bioassay experiment

[0221] 1. Test insects: 3rd instar Oriental armyworm (Mythimna separata Walker), provided by the Pollution-free Pesticide Research Center of Northwest Agriculture and Forestry University.

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

[0223] 3. Bioassay method:

[0224] Leaf butterfly addition method (Zhang Xing and Zhao Shanhuan 1983): Use acetone as blank control and toosendanin as agent control to determine the activity of the test compound at a concentration of 1 mg / mL; spread a layer of filter paper on the bottom of a 9 cm diameter glass culture dish and add water to keep it moist. Pick 10 early 3rd instar larvae from each dish, and set three replicates for each treatment sample. Remove the main veins from the freshly picked oat leaves and cut them into 1×1 cm 2 The small leaf butterflies are immersed in the pre-prepared test solution and control solution for 3 seconds, and then fed to test insects after natural drying; they are raised under the conditions of room temperature of about 25℃, humidity of 35%-80%, and light time of 12h / 12h. After the test insects have eaten the oat leaves, the leaf butterflies with the solution are added. After 48 hours of breeding, they are fed with fresh leaves without the solution until they emerge. The feeding amount, number of survivors, symptoms, etc. of the test insects are recorded regularly; the test results are used to calculate the corrected mortality rate (%) of the test insects at different stages according to the following formula.

[0225]

[0226] Table 2. Gastric poison activity of capsaicin (a), intermediate (bd) and derivatives 1-36 of the present invention against oriental armyworm

[0227]

[0228]

[0229] The results show that the control effects of compounds 1-36 on oriental armyworms are all improved compared with capsaicin, and the final mortality of some capsaicin ester derivatives (3, 6, 7, 9, 13, 15-18, 20, 27, 32, 34) on oriental armyworms is 51.4%-65.7%, which is higher than the commercialized toosendanin (48.6%). This shows that the compounds of the present invention have good growth and development activity against lepidopteran pests represented by oriental armyworms, and therefore are expected to be used in the preparation of environmentally friendly, low-toxic botanical insecticides.

Claims

1. A capsaicin ester derivative, characterized in that: Its chemical structure is shown in formula (I), Wherein, R is selected from an alkyl group, a phenyl group, a substituted phenyl group or an unsubstituted cinnamyl group.

2. The capsaicin ester derivative according to claim 1, characterized in that 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 = 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.

3. Use of the capsaicin ester derivatives according to claim 1 or 2 for preparing insecticides.

4. Use of the capsaicin ester derivatives according to claim 1 or 2 for preparing insecticides for lepidopteran pests.

5. Use of the capsaicin ester derivatives according to claim 1 or 2 for preparing acaricides.

6. The method for preparing capsaicin ester compounds according to claim 1, characterized in that: The preparation method comprises: Step 1, capsaicin reacts with 1-bromo-3-methyl-2-butene to obtain intermediate b, the structural formula of intermediate b is shown in formula (II): Step 2, intermediate b reacts with tin dioxide to obtain intermediate c, wherein the intermediate c has a structural formula as shown in formula (III): Step 3, intermediate c is subjected to reduction reaction to obtain intermediate d, wherein the intermediate d has a structural formula as shown in formula (IV): Step 4, the intermediate d is reacted with RCOOH to prepare a compound represented by formula (I), wherein R is selected from alkyl, substituted or unsubstituted phenyl, and unsubstituted cinnamyl.

7. The method for preparing capsaicin ester derivatives according to claim 5, characterized in that: The reaction in step 2 is carried out in a dimethyl sulfoxide solution at a reaction temperature of 100-110° C. and a reaction time of 20-30 min.

8. The method for preparing capsaicin ester derivatives according to claim 5, characterized in that: Step 4 The reaction is carried out in anhydrous dichloromethane, while adding 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP), and the reaction temperature is 20-30°C.

9. The method for preparing capsaicin ester derivatives according to claim 5, characterized in that: The RCOOH is selected from one of 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.

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