Abstract
Due to the extensive use of agrochemicals resulting in the emergence of pesticide resistance and ecological environment problems, the research and development of new alternatives for crop protection is highly desirable. In order to discover potent natural product-based insecticide candidates, a series of new cholesterol ester derivatives containing cinnamic acid-like fragments at the C-7 position were synthesized. Some derivatives showed potent pesticidal activities. Against Mythimna separata Walker, compounds 2a, Id, Ig, and IIg showed 2.1–2.4-fold growth-inhibitory activity of the precursor cholesterol. Against Plutella xylostella Linnaeus, compounds Ig, IIf, and IIi exhibited 1.9–2.1-fold insecticidal activity of cholesterol. These results will pave the way for the future synthesis of cholesterol-based derivatives as agrochemicals.
Keywords: cholesterol, cinnamic acid, structural modification, agricultural activity
1. Introduction
Cholesterol (1), a biological endogenous substance, has shown a variety of antitumor, antioxidant, anti-inflammatory, and insecticide activities [1,2,3,4,5,6,7,8,9,10]. Cinnamic acid (Figure 1), as a main component of Cinnamomum cassia Presl, has displayed a range of pharmaceutical and agricultural activities [11,12,13]. In addition, several cholesterol oxime esters containing cinnamic acid-like fragments (1′) have shown promising insecticidal activities [14]. Nowadays, due to the extensive and irrational use of chemical insecticides resulting in pest resistance and ecological environment problems, the research and development of new pesticides for crop protection is highly desirable [15,16,17,18]. Because of the characteristics of natural secondary metabolites as an unparalleled source of bioactive products, currently, the study of natural product-based insecticides as an important alternative to classic agrochemicals has received much attention [19,20,21]. Therefore, in order to develop prospective cholesterol-based pesticide candidates, a series of new cholesterol derivatives I and II (Figure 1) were designed and synthesized by a combination of cholesterol and cinnamic acid-like fragments via the ester bond at the C-7 position of cholesterol. Meanwhile, two typically crop-threatening insect pests, Mythimna separata Walker (Lepidoptera: Noctuidae) and Plutella xylostella Linnaeus (Lepidoptera: Plutellidae), were used as the tested biotargets for assessment of the insecticidal activities of cholesterol derivatives I and II [22,23].
Figure 1.
Design of cholesterol esters derivatives I and II.
2. Materials and Methods
Multi-generation sensitive strains of Mythimna separata and Plutella xylostella (3rd instar larvae) were raised in our lab. Cholesterol was purchased from Aladdin Chemistry Co., Ltd. (Shanghai, China). The melting point (mp) was determined using the XT-415 digital melting point apparatus (Beijing Tech Instruments, Ltd., Beijing, China) and was uncorrected. 1H NMR spectra (Supplementary Materials) were obtained using Avance III 500 MHz equipment (Bruker, Germany). High-resolution mass spectra (HRMS) were obtained with a MicrOTOF Q II instrument (Bruker, Germany). Infrared spectroscopy (IR) was obtained with a TENSOR-27 instrument (Bruker, Germany).
2.1. Synthesis of Compounds 2a and 2b
A mixture of cholesterol (1, 5 mmol), triethylamine (10 mmol), and substituted acyl chloride (7 mmol) in dry CH2Cl2 (20 mL) was stirred at room temperature for 14 or 17 h. Then, CH2Cl2 (30 mL) was added to the mixture, which was washed with brine. The organic phase was dried over anhydrous Na2SO4 and purified by silica gel column chromatography eluting with petroleum ether/dichloromethane (4/1, v/v) to obtain 2a and 2b.
Data for 2a: CAS: 604-32-0. Yield: 79%, white solid, mp 188–190 °C; IR cm−1 (KBr): 2948, 1717, 1656, 1531, 1454, 1370, 1271, 1110, 710; 1H NMR (500 MHz, CDCl3) δ: 8.05 (d, J = 7.5 Hz, 2H, Ar-H), 7.56 (t, J = 7.5 Hz, 1H, Ar-H), 7.44 (t, J = 7.5 Hz, 2H, Ar-H), 5.42 (d, J = 5.0 Hz, 1H, H-6), 4.83–4.89 (m, 1H, H-3), 2.47 (d, J = 8.5 Hz, 2H), 1.97–2.03 (m, 3H), 1.90–1.93 (m, 1H), 1.80–1.86 (m, 1H), 1.69–1.78 (m, 1H), 1.45–1.61 (m, 7H), 1.33–1.38 (m, 3H), 1.09–1.27 (m, 8H), 1.07 (s, 3H), 0.99–1.02 (m, 2H), 0.93 (d, J = 6.5 Hz, 3H), 0.87 (s, 3H), 0.86 (s, 3H), 0.69 (s, 3H). HRMS (ESI): calcd for C34H50O2Na ([M + Na]+), 513.3616; found, 513.3709.
Data for 2b: CAS: 30591-44-7. Yield: 89%, white solid, mp 180–182 °C; IR cm−1 (KBr): 2949, 2859, 1710, 1464, 1276, 1112, 750; 1H NMR (500 MHz, CDCl3) δ: 7.93 (d, J = 8.0 Hz, 2H, Ar-H), 7.23 (d, J = 8.0 Hz, 2H, Ar-H), 5.42 (d, J = 5.0 Hz, 1H, H-6), 4.81–4.87 (m, 1H, H-3), 2.46 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H), 1.97–2.03 (m, 3H), 1.89–1.92 (m, 1H), 1.82–1.85 (m, 1H), 1.68–1.76 (m, 1H), 1.46–1.59 (m, 7H), 1.33–1.38 (m, 3H), 1.09–1.27 (m, 8H), 1.06 (s, 3H), 0.99–1.02 (m, 2H), 0.92 (d, J = 6.5 Hz, 3H), 0.87 (s, 3H), 0.86 (s, 3H), 0.68 (s, 3H). HRMS (ESI): calcd for C35H52O2Na ([M + Na]+), 527.3865; found, 527.3862.
2.2. Synthesis of Compounds 3a and 3b
A mixture of compounds 2a and 2b (4 mmol), CrO3 (4 mmol), pyridine (8 mmol), and 70% t-BuOOH (40 mmol) in dry CH2Cl2 (30 mL) was stirred at room temperature for 5 or 12 h. The mixture was extracted by CH2Cl2 (30 mL × 2). The combined organic phase was washed with saturated aq. NaHSO3 (15 mL × 3) and brine (15 mL), dried over anhydrous Na2SO4 and purified by silica gel column chromatography eluting with petroleum ether/dichloromethane (1/3, v/v), yielded 3a and 3b.
Data for 3a: CAS: 6997-41-7. Yield: 93%, white solid, mp 158–160 °C; IR cm−1 (KBr): 2944, 2866, 1717, 1667, 1459, 1275, 1113, 712; 1H NMR (500 MHz, CDCl3) δ: 8.05 (d, J = 7.5 Hz, 2H, Ar-H), 7.58 (t, J = 7.5 Hz, 1H, Ar-H), 7.46 (t, J = 7.5 Hz, 2H, Ar-H), 5.75 (s, 1H, H-6), 4.94–5.01 (m, 1H, H-3), 2.60–2.72 (m, 2H), 2.38–2.43 (m, 1H), 2.23–2.28 (m, 1H), 2.11–2.14 (m, 1H), 2.01–2.06 (m, 2H), 1.79–1.94 (m, 2H), 1.48–1.61 (m, 5H), 1.34–1.39 (m, 5H), 1.26 (s, 3H), 1.07–1.15 (m, 6H), 1.01–1.04 (m, 1H), 0.93 (d, J = 6.5 Hz, 3H), 0.87 (s, 3H), 0.86 (s, 3H), 0.69 (s, 3H). HRMS (ESI): calculated for C34H48O3Na ([M + Na]+), 527.3506; found, 527.3501.
Data for 3b: Yield: 74%, white solid, mp 161–162 °C; IR cm−1 (KBr): 2949, 2865, 1715, 1667, 1461, 1278, 1112, 746; 1H NMR (500 MHz, CDCl3) δ: 7.93 (d, J = 7.5 Hz, 2H, Ar-H), 7.24 (d, J = 8.0 Hz, 2H, Ar-H), 5.74 (s, 1H, H-6), 4.92–4.99 (m, 1H, H-3), 2.58–2.71 (m, 2H), 2.41 (s, 3H), 2.23–2.27 (m, 1H), 2.09–2.14 (m, 1H), 2.00–2.06 (m, 2H), 1.89–1.94 (m, 1H), 1.78–1.83 (m, 1H), 1.48–1.59 (m, 4H), 1.27–1.39 (m, 7H), 1.25 (s, 3H), 1.06–1.18 (m, 6H), 1.00–1.04 (m, 1H), 0.93 (d, J = 6.5 Hz, 3H), 0.87 (d, J = 2.0 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.69 (s, 3H). HRMS (ESI): calculated for C35H50O3Na ([M + Na]+), 541.3658; found, 541.3659.
2.3. Synthesis of Compounds 4a and 4b
Compound 3a or b (4 mmol) was dissolved in methanol/dichloromethane (1/1, v/v), and sodium borohydride (6 mmol) was added in batches under an ice bath. Then, it was raised naturally to room temperature. When the reaction was complete, methanol was removed and ethyl acetate (30 mL) was added to the mixture, which was washed with brine. The organic phase was dried over anhydrous Na2SO4, concentrated, and purified by silica gel column chromatography eluting with petroleum ether/dichloromethane (1/1, v/v) to obtain 4a and 4b.
Data for 4a: CAS: 17974-80-0. Yield: 65%, white solid, mp 192–193 °C; IR cm−1 (KBr): 3490, 2946, 2859, 1691, 1456, 1282, 1122, 708; 1H NMR (500 MHz, CDCl3) δ: 8.05 (d, J = 7.5 Hz, 2H, Ar-H), 7.56 (t, J = 7.5 Hz, 1H, Ar-H), 7.45 (t, J = 7.5 Hz, 2H, Ar-H), 5.36 (s, 1H, H-6), 4.85–4.91 (m, 1H, H-3), 3.89 (d, J = 8.0 Hz, 1H, H-7), 2.48–2.50 (m, 2H), 2.02–2.04 (m, 2H), 1.86–1.93 (m, 2H), 1.70–1.84 (m, 2H), 1.28–1.58 (m, 12H), 1.14–1.22 (m, 6H), 1.11 (s, 3H), 0.98–1.04 (m, 1H), 0.93 (d, J = 6.5 Hz, 3H), 0.88 (d, J = 2.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.70 (s, 3H). HRMS (ESI): calculated for C34H50O3Na ([M + Na]+), 529.3645; found, 529.3658.
Data for 4b: Yield: 68%, white solid, mp 189–191 °C; IR cm−1 (KBr): 3483, 2948, 2861, 1688, 1285, 1121, 1026, 751; 1H NMR (500 MHz, CDCl3) δ: 7.93 (d, J = 8.0 Hz, 2H, Ar-H), 7.23 (d, J = 8.0 Hz, 2H, Ar-H), 5.35 (s, 1H, H-6), 4.83–4.89 (m, 1H, H-3), 3.89 (d, J = 8.0 Hz, 1H, H-7), 2.46–2.49 (m, 2H), 2.40 (s, 3H), 1.99–2.04 (m, 2H), 1.86–1.92 (m, 2H), 1.72–1.82 (m, 2H), 1.30–1.56 (m, 12H), 1.12–1.21 (m, 6H), 1.11 (s, 3H), 1.00–1.04 (m, 1H), 0.93 (d, J = 6.5 Hz, 3H), 0.87 (d, J = 2.5 Hz, 3H), 0.86 (d, J = 2.5 Hz, 3H), 0.70 (s, 3H). HRMS (ESI): calculated for C35H52O3Na ([M + Na]+), 543.3814; found, 543.3814.
2.4. General Procedure for Synthesis of Target Compounds I(a–i)–II(a–i)
Compound 4a or 4b (0.4 mmol) reacted with cinnamic acids (5a–i, 0.6 mmol) in dry CH2Cl2 (5 mL) in the presence of EDCI (0.6 mmol) and DMAP (0.2 mmol) at room temperature for 10–34 h. Then, the mixture was diluted with CH2Cl2 (20 mL). It was washed with brine, dried over anhydrous Na2SO4, and purified by PTLC eluting with petroleum ether/dichloromethane (v/v = 4:1) or petroleum ether/ethyl acetate (v/v = 15:1) to afford I(a–i)–II(a–i) in 14−53% yields.
Data forIa: Yield: 18%, white solid, mp 105–106 °C; IR cm−1 (KBr): 2946, 2863, 1712, 1634, 1497, 1451, 1266, 1244, 1269, 1110, 710; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 8.0 Hz, 2H, Ar-H), 7.59 (d, J = 16.0 Hz, 1H, H-3′), 7.52–7.54 (m, 1H, Ar-H), 7.41–7.44 (m, 2H, Ar-H), 7.00–7.04 (m, 2H, Ar-H), 6.81 (d, J = 8.0 Hz, 1H, Ar-H), 6.26 (d, J = 16.0 Hz, 1H, H-2′), 6.00 (s, 2H, –OCH2O–), 5.35 (s, 1H, H-6), 5.20 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.49 (d, J = 8.5 Hz, 2H), 2.03–2.06 (m, 2H), 1.92–1.96 (m, 1H), 1.73–1.83 (m, 3H), 1.47–1.59 (m, 5H), 1.30–1.36 (m, 4H), 1.19–1.24 (m, 4H), 1.16 (s, 3H), 1.06–1.13 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.84 (d, J = 2.0 Hz, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C44H56O6Na ([M + Na]+), 703.3975; found, 703.3979.
Data forIb: Yield: 21%, white solid, mp 106–107 °C; IR cm−1 (KBr): 2944, 2864, 1711, 1636, 1507, 1459, 1280, 1243, 1167, 708; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 7.5 Hz, 2H, Ar-H), 7.52–7.57 (m, 2H), 7.44 (t, J = 7.5 Hz, 2H, Ar-H), 7.02–7.05 (m, 2H, Ar-H), 6.85 (d, J = 8.0 Hz, 1H, Ar-H), 6.28 (d, J = 15.5 Hz, 1H, H-2´), 5.36 (s, 1H, H-6), 5.20 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 4.25–4.28 (m, 4H, –OCH2CH2O–), 2.49 (d, J = 8.5 Hz, 2H), 2.02–2.07 (m, 2H), 1.93–1.95 (m, 1H), 1.73–1.81 (m, 3H), 1.47–1.62 (m, 5H), 1.29–1.34 (m, 4H), 1.19–1.22 (m, 4H), 1.16 (s, 3H), 1.05–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.84 (d, J = 2.0 Hz, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C45H58O6Na ([M + Na]+), 717.4134; found, 717.4131.
Data for Ic: Yield: 32%, white solid, mp 106–108 °C; IR cm−1 (KBr): 2959, 2858, 1723, 1639, 1455, 1213, 679; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 7.5 Hz, 2H, Ar-H), 7.69 (d, J = 16.0 Hz, 1H, H-3′), 7.52–7.55 (m, 3H, Ar-H), 7.41–7.44 (m, 2H, Ar-H), 7.37–7.38 (m, 3H, Ar-H), 6.44 (d, J = 16.0 Hz, 1H, H-2′), 5.36 (s, 1H, H-6), 5.22 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.50 (d, J = 8.0 Hz, 2H), 2.03–2.07 (m, 2H), 1.93–1.97 (m, 1H), 1.73–1.83 (m, 3H), 1.47–1.60 (m, 5H), 1.29–1.33 (m, 4H), 1.20–1.24 (m, 4H), 1.17 (s, 3H), 1.04–1.14 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.84 (d, J = 2.5 Hz, 3H), 0.73 (s, 3H). HRMS (ESI): calculated for C43H56O4Na ([M + Na]+), 659.4030; found, 659.4076.
Data for Id: Yield: 14%, white solid, mp 89–91 °C; IR cm−1 (KBr): 2955, 2860, 1713, 1640, 1510, 1457, 1276, 1231, 1168, 705; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 7.5 Hz, 2H, Ar-H), 7.65 (d, J = 16.0 Hz, 1H, H-3′), 7.50–7.56 (m, 3H, Ar-H), 7.44 (t, J = 7.5 Hz, 2H, Ar-H), 7.05–7.08 (m, 2H, Ar-H), 6.36 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.22 (d, J = 9.0 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.50 (d, J = 8.0 Hz, 2H), 2.03–2.06 (m, 2H), 1.93–1.97 (m, 1H), 1.73–1.82 (m, 3H), 1.47–1.60 (m, 5H), 1.29–1.33 (m, 4H), 1.19–1.22 (m, 4H), 1.17 (s, 3H), 1.06–1.12 (m, 4H), 0.97–0.99 (m, 1H), 0.93 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.84 (d, J = 2.0 Hz, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C43H55FO4Na ([M + Na]+), 677.3951; found, 677.3982.
Data for Ie: Yield: 29%, white solid, mp 115–117 °C; IR cm−1 (KBr): 2944, 2862, 1711, 1635, 1507, 1459, 1278, 1167, 1116, 1069, 710; 1H NMR (500 MHz, CDCl3) δ: 8.02–8.04 (m, 2H, Ar-H), 7.63 (d, J = 16.0 Hz, 1H, H-3′), 7.52–7.56 (m, 1H, Ar-H), 7.41–7.46 (m, 4H, Ar-H), 7.34–7.36 (m, 2H, Ar-H), 6.40 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.50 (d, J = 8.0 Hz, 2H), 2.02–2.07 (m, 2H), 1.93–1.97 (m, 1H), 1.73–1.84 (m, 3H), 1.41–1.63 (m, 5H), 1.27–1.34 (m, 4H), 1.19–1.24 (m, 4H), 1.16 (s, 3H), 1.06–1.13 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 1.5 Hz, 3H), 0.84 (d, J = 2.0 Hz, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C43H55ClO4Na ([M + Na]+), 693.3681; found, 693.3687.
Data for If: Yield: 18%, white solid, mp 112–114 °C; IR cm−1 (KBr): 2945, 2860, 1711, 1638, 1456, 1273, 1171, 816, 706; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 7.5 Hz, 2H, Ar-H), 7.61 (d, J = 16.0 Hz, 1H, H-3′), 7.50–7.56 (m, 3H, Ar-H), 7.41–7.44 (m, 2H, Ar-H), 7.37–7.39 (m, 2H, Ar-H), 6.42 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.49 (d, J = 8.0 Hz, 2H), 2.03–2.06 (m, 2H), 1.93–1.96 (m, 1H), 1.70–1.84 (m, 3H), 1.45–1.62 (m, 5H), 1.30–1.35 (m, 4H), 1.20–1.24 (m, 4H), 1.16 (s, 3H), 1.06–1.13 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 4.0 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C43H55BrO4Na ([M + Na]+), 737.3172, 739.3169; found, 737.3181, 739.3161.
Data for Ig: Yield: 20%, white solid, mp 98–100 °C; IR cm−1 (KBr): 2949, 2864, 1715, 1641, 1275, 1173, 1123, 1037, 1013, 985, 833, 709; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 8.0 Hz, 2H, Ar-H), 7.69 (d, J = 16.0 Hz, 1H, H-3′), 7.63 (s, 4H, Ar-H), 7.53–7.56 (m, 1H, Ar-H), 7.41–7.44 (m, 2H, Ar-H), 6.51 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.23 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.50 (d, J = 8.5 Hz, 2H), 2.04–2.06 (m, 2H), 1.94–1.97 (m, 1H), 1.73–1.83 (m, 3H), 1.45–1.62 (m, 5H), 1.30–1.36 (m, 4H), 1.22–1.25 (m, 4H), 1.17 (s, 3H), 1.07–1.12 (m, 4H), 0.98–1.01 (m, 1H), 0.93 (d, J = 6.0 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.73 (s, 3H). HRMS (ESI): calculated for C44H55F3O4Na ([M + Na]+), 727.3950; found, 727.3958.
Data for Ih: Yield: 53%, white solid, mp 90–92 °C; IR cm−1 (KBr): 2945, 2862, 1713, 1638, 1456, 1274, 1169, 808, 708; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 7.5 Hz, 2H, Ar-H), 7.66 (d, J = 16.0 Hz, 1H, H-3′), 7.53–7.55 (m, 1H, Ar-H), 7.41–7.43 (m, 4H, Ar-H), 7.19 (d, J = 7.5 Hz, 2H, Ar-H), 6.39 (d, J = 16.5 Hz, 1H, H-2′), 5.36 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 2.50 (d, J = 8.5 Hz, 2H), 2.37 (s, 3H), 2.03–2.05 (m, 2H), 1.93–1.96 (m, 1H), 1.73–1.82 (m, 3H), 1.46–1.64 (m, 5H), 1.30–1.36 (m, 4H), 1.22–1.25 (m, 4H), 1.17 (s, 3H), 1.06–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 4.5 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.73 (s, 3H). HRMS (ESI): calculated for C44H58O4Na ([M + Na]+), 673.4227; found, 673.6233.
Data for Ii: Yield: 30%, white solid, mp 100–102 °C; IR cm−1 (KBr): 2945, 2862, 1710, 1635, 1605, 1260, 1166, 824, 708; 1H NMR (500 MHz, CDCl3) δ: 8.04 (d, J = 7.0 Hz, 2H, Ar-H), 7.64 (d, J = 16.0 Hz, 1H, H-3′), 7.52–7.55 (m, 1H, Ar-H), 7.46–7.49 (m, 2H, Ar-H), 7.44 (t, J = 7.5 Hz, 2H, Ar-H), 6.88–6.91 (m, 2H, Ar-H), 6.30 (d, J = 15.5 Hz, 1H, H-2′), 5.36 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.85–4.91 (m, 1H, H-3), 3.83 (s, 3H), 2.50 (d, J = 8.5 Hz, 2H), 2.03–2.05 (m, 2H), 1.93–1.96 (m, 1H), 1.72–1.84 (m, 3H), 1.46–1.60 (m, 5H), 1.30–1.38 (m, 4H), 1.22–1.25 (m, 4H), 1.16 (s, 3H), 1.06–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 3.5 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C44H58O5Na ([M + Na]+), 689.4197; found, 689.4182.
Data for IIa: Yield: 16%, white solid, mp 98–100 °C; IR cm−1 (KBr): 2952, 2860, 1702, 1635, 1451, 1231, 1109, 808, 704; 1H NMR (500 MHz, CDCl3) δ: 7.91–8.04 (m, 2H, Ar-H), 7.59 (d, J = 16.0 Hz, 1H, H-3′), 7.44 (t, J = 7.5 Hz, 1H, Ar-H), 7.23 (d, J = 8.0 Hz, 1H, Ar-H), 7.00–7.03 (m, 2H, Ar-H), 6.81 (d, J = 7.5 Hz, 1H, Ar-H), 6.26 (d, J = 16.0 Hz, 1H, H-2′), 6.00 (s, 2H, –OCH2O–), 5.35 (s, 1H, H-6), 5.20 (d, J = 8.5 Hz, 1H, H-7), 4.83–4.91 (m, 1H, H-3), 2.47–2.50 (m, 2H), 2.40 (s, 2H), 2.03–2.05 (m, 2H), 1.92–1.95 (m, 1H), 1.71–1.83 (m, 3H), 1.59–1.62 (m, 2H), 1.47–1.54 (m, 3H), 1.30–1.36 (m, 4H), 1.18–1.24 (m, 5H), 1.16 (s, 3H), 1.06–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 6.0 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C45H58O6Na ([M + Na]+), 717.4131; found, 717.4138.
Data for IIb: Yield: 21%, white solid, mp 107–109 °C; IR cm−1 (KBr): 2941, 2861, 1711, 1638, 1509, 1461, 1280, 805, 748; 1H NMR (500 MHz, CDCl3) δ: 7.92 (d, J = 8.0 Hz, 2H, Ar-H), 7.57 (d, J = 16.0 Hz, 1H, H-3´), 7.23 (d, J = 8.0 Hz, 2H, Ar-H), 7.02–7.05 (m, 2H, Ar-H), 6.86 (d, J = 8.5 Hz, 1H, Ar-H), 6.28 (d, J = 16.0 Hz, 1H, H-2´), 5.35 (s, 1H, H-6), 5.19 (d, J = 8.5 Hz, 1H, H-7), 4.83–4.89 (m, 1H, H-3), 4.26–4.29 (m, 4H, –OCH2CH2O–), 2.48 (d, J = 8.5 Hz, 2H), 2.40 (s, 3H), 2.01–2.05 (m, 2H), 1.91–1.95 (m, 1H), 1.74–1.79 (m, 3H), 1.44–1.54 (m, 5H), 1.29–1.31 (m, 3H), 1.20–1.22 (m, 5H), 1.16 (s, 3H), 1.05–1.09 (m, 4H), 0.99–1.00 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.84 (d, J = 2.5 Hz, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C46H60O6Na ([M + Na]+), 731.4288; found, 731.4285.
Data for IIc: Yield: 45%, white solid, mp 112–114 °C; IR cm−1 (KBr): 2940, 2862, 1706, 1640, 1273, 1175, 1112, 990, 944, 758; 1H NMR (500 MHz, CDCl3) δ: 7.93 (d, J = 8.0 Hz, 2H, Ar-H), 7.69 (d, J = 16.0 Hz, 1H, H-3′), 7.51–7.53 (m, 2H, Ar-H), 7.36–7.38 (m, 3H, Ar-H), 7.22 (d, J = 8.0 Hz, 2H, Ar-H), 6.44 (d, J = 16.0 Hz, 1H, H-2′), 5.36 (s, 1H, H-6), 5.22 (d, J = 8.5 Hz, 1H, H-7), 4.83–4.90 (m, 1H, H-3), 2.49 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H), 2.03–2.05 (m, 2H), 1.92–1.95 (m, 1H), 1.72–1.85 (m, 3H), 1.46–1.61 (m, 4H), 1.30–1.38 (m, 4H), 1.19–1.26 (m, 5H), 1.16 (s, 3H), 1.03–1.13 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.0 Hz, 3H), 0.84 (d, J = 2.0 Hz, 3H), 0.72 (s, 3H). HRMS [ESI]: calculated for C44H58O4Na ([M + Na]+), 673.4233; found, 673.4231.
Data for IId: Yield: 19%, white solid, mp 108–110 °C; IR cm−1 (KBr): 2948, 2863, 1712, 1639, 1609, 1274, 1168, 1108, 829, 748; 1H NMR (500 MHz, CDCl3) δ: 7.92 (d, J = 7.5 Hz, 2H, Ar-H), 7.64 (d, J = 16.0 Hz, 1H, H-3′), 7.50–7.52 (m, 2H, Ar-H), 7.23 (d, J = 8.5 Hz, 2H, Ar-H), 7.05–7.08 (m, 2H, Ar-H), 6.36 (d, J = 16.5 Hz, 1H, H-2′), 5.34 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.83–4.89 (m, 1H, H-3), 2.49 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H), 2.03–2.05 (m, 2H), 1.93–1.95 (m, 1H), 1.69–1.82 (m, 3H), 1.57–1.63 (m, 2H), 1.45–1.50 (m, 3H), 1.31–1.36 (m, 4H), 1.21–1.25 (m, 4H), 1.16 (s, 3H), 1.06–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 5.0 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C44H57FO4Na ([M + Na]+), 691.4139; found, 691.4138.
Data for IIe: Yield: 27%, white solid, mp 96–98 °C; IR cm−1 (KBr): 2927, 2854, 1727, 1643, 1215, 1113, 806, 690; 1H NMR (500 MHz, CDCl3) δ: 7.92 (d, J = 8.0 Hz, 2H, Ar-H), 7.63 (d, J = 16.0 Hz, 1H, H-3′), 7.44–7.46 (m, 2H, Ar-H), 7.33–7.36 (m, 2H, Ar-H), 7.23 (d, J = 8.0 Hz, 2H, Ar-H), 6.40 (d, J = 16.0 Hz, 1H, H-2′), 5.34 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.83–4.89 (m, 1H, H-3), 2.48 (d, J = 8.5 Hz, 2H), 2.40 (s, 3H), 2.03–2.06 (m, 2H), 1.92–1.95 (m, 1H), 1.74–1.81 (m, 3H), 1.44–1.55 (m, 5H), 1.29–1.31 (m, 3H), 1.19–1.23 (m, 5H), 1.16 (s, 3H), 1.06–1.10 (m, 4H), 0.97–0.99 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.86 (d, J = 2.5 Hz, 3H), 0.84 (d, J = 2.0 Hz, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C44H57ClO4Na ([M + Na]+), 707.3843; found, 707.3843.
Data for IIf: Yield: 20%, white solid, mp 96–98 °C; IR cm−1 (KBr): 2946, 2862, 1713, 1637, 1272, 1171, 1110, 818, 748; 1H NMR (500 MHz, CDCl3) δ: 7.91–8.04 (m, 2H, Ar-H), 7.61 (d, J = 16.0 Hz, 1H, H-3′), 7.52 (d, J = 7.0 Hz, 2H, Ar-H), 7.39 (d, J = 7.0 Hz, 2H, Ar-H), 7.23 (d, J = 7.0 Hz, 2H, Ar-H), 6.42 (d, J = 16.0 Hz, 1H, H-2′), 5.34 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.84–4.90 (m, 1H, H-3), 2.48 (d, J = 8.5 Hz, 2H), 2.40 (s, 2H), 2.03–2.06 (m, 2H), 1.93–1.95 (m, 1H), 1.72–1.84 (m, 3H), 1.59–1.63 (m, 2H), 1.44–1.52 (m, 3H), 1.30–1.37 (m, 4H), 1.20–1.26 (m, 5H), 1.16 (s, 3H), 1.04–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 4.5 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C44H57BrO4Na ([M + Na]+), 751.3338; found, 751.3333.
Data for IIg: Yield: 18%, white solid, mp 84–86 °C; IR cm−1 (KBr): 2948, 2864, 1715, 1275, 1173, 1122, 833, 748; 1H NMR (500 MHz, CDCl3) δ: 7.92 (d, J = 7.5 Hz, 2H, Ar-H), 7.69 (d, J = 16.0 Hz, 1H, H-3′), 7.63 (s, 4H, Ar-H), 7.23 (d, J = 8.0 Hz, 2H, Ar-H), 6.50 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.23 (d, J = 8.0 Hz, 1H, H-7), 4.82–4.90 (m, 1H, H-3), 2.49 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H), 2.03–2.06 (m, 2H), 1.93–1.96 (m, 1H), 1.67–1.85 (m, 4H), 1.47–1.62 (m, 4H), 1.30–1.41 (m, 4H), 1.21–1.23 (m, 4H), 1.17 (s, 3H), 1.06–1.12 (m, 4H), 0.96–1.01 (m, 1H), 0.93 (d, J = 6.0 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.73 (s, 3H). HRMS (ESI): calculated for C45H57F3O4Na ([M + Na]+), 741.4107; found, 741.4101.
Data for IIh: Yield: 26%, white solid, mp 93–95 °C; IR cm−1 (KBr): 2947, 2863, 1712, 1635, 1272, 1169, 1109, 811, 749; 1H NMR (500 MHz, CDCl3) δ: 7.92 (d, J = 7.5 Hz, 2H, Ar-H), 7.66 (d, J = 16.0 Hz, 1H, H-3′), 7.43 (d, J = 7.5 Hz, 2H, Ar-H), 7.23 (d, J = 7.5 Hz, 2H, Ar-H), 7.19 (d, J = 7.5 Hz, 2H, Ar-H), 6.39 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.82–4.89 (m, 1H, H-3), 2.49 (d, J = 8.5 Hz, 2H), 2.40 (s, 3H), 2.37 (s, 3H), 2.03–2.05 (m, 2H), 1.92–1.95 (m, 1H), 1.71–1.84 (m, 3H), 1.60 (s, 2H), 1.47–1.54 (m, 3H), 1.30–1.41 (m, 4H), 1.19–1.23 (m, 4H), 1.16 (s, 3H), 1.03–1.12 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 4.5 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C45H60O4Na ([M + Na]+), 687.4389; found, 687.4390.
Data for IIi: Yield: 34%, white solid, mp 97–99 °C; IR cm−1 (KBr): 2946, 2863, 1711, 1634, 1607, 1263, 1167, 826, 749; 1H NMR (500 MHz, CDCl3) δ: 7.91–8.04 (m, 2H, Ar-H), 7.64 (d, J = 16.0 Hz, 1H, H-3′), 7.48 (d, J = 7.5 Hz, 2H, Ar-H), 7.23 (d, J = 7.5 Hz, 2H, Ar-H), 6.90 (d, J = 8.0 Hz, 2H, Ar-H), 6.31 (d, J = 16.0 Hz, 1H, H-2′), 5.35 (s, 1H, H-6), 5.21 (d, J = 8.5 Hz, 1H, H-7), 4.83–4.90 (m, 1H, H-3), 3.83 (s, 3H), 2.47–2.50 (m, 2H), 2.40 (s, 3H), 2.03–2.05 (m, 2H), 1.92–1.95 (m, 1H), 1.69–1.82 (m, 3H), 1.61 (s, 2H), 1.46–1.54 (m, 3H), 1.31–1.37 (m, 4H), 1.20–1.23 (m, 4H), 1.16 (s, 3H), 1.03–1.13 (m, 4H), 0.97–1.01 (m, 1H), 0.92 (d, J = 5.0 Hz, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H). HRMS (ESI): calculated for C45H60O5Na ([M + Na]+), 703.4338; found, 703.4337.
2.5. Biological Assay
2.5.1. Insecticidal Activity of Compounds I(a–i)–II(a–i) against M. separata
Thirty-six early 3rd-instar larvae of M. separata were selected as the tested insects for each compound. Solutions of tested compounds (rotenone as a positive control) were prepared in acetone (containing 0.5% N-methylpyrrolidone) at 1 mg/mL. After being dipped into the corresponding solution for 3 s, wheat leaf discs (1 × 1 cm) were taken out and dried. Wheat leaf discs were treated by acetone (containing 0.5% N-methylpyrrolidone) alone as the blank control group (CK). Some of the above discs were added to each culture dish (12 insects per dish). Once the discs were consumed, additional ones were added. After 48 h, the rest of compound-soaked discs were cleaned out, and the untreated ones were added until the end of pupae (temperature: 25 ± 2 °C; RH: 65–80%; photoperiod: light/dark = 12 h/12 h). Their corrected final mortality rate values were calculated as follows: corrected mortality rate (%) = (T − C) × 100/(100% − C); C is the mortality rate of CK, and T is the mortality rate of the treated M. separata [4,24].
2.5.2. Insecticidal Activity of Compounds I(a–i)–II(a–i) against P. xylostella
For each compound, 45 3rd-instar larvae of P. xylostella were selected. Solutions of tested compounds (β-cypermethrin as a positive control) were prepared in acetone (containing 0.5% N-methylpyrrolidone) at 1 mg/mL. Fresh cabbage leaf discs (0.5 × 0.5 cm) were dipped into the corresponding solution for 3 s and dried. Fresh cabbage leaf discs (0.5 × 0.5 cm) were treated by acetone (containing 0.5% N-methylpyrrolidone) alone as the blank control group (CK). Some of the above discs were added to each culture dish (15 insects per dish). Once the discs were consumed, additional ones were added (temperature: 25 ± 2 °C; RH: 65–80%; photoperiod: light/dark = 14 h/10 h). Their 24 and 48 h corrected mortality rate values were calculated in the same way as mentioned above. Finally, the 48 h LC50 values of some potent compounds were calculated [24].
3. Results and Discussion
3.1. Chemistry
As shown in Scheme 1, intermediates 2a and 2b were prepared in 79 and 89% yields from one reacting with acyl chlorides [4,24]. Then, compounds 2a and 2b were oxidized by CrO3/t-BuOOH to give compounds 3a and 3b in 93% and 74% yields, respectively. In the presence of sodium borohydride, to our delight, the carbonyl group at the C-7 position of 3a and 3b was stereoselectively reduced to β-OH, and the corresponding compounds 4a and 4b were obtained in 65% and 68% yields, respectively. Finally, compounds 4a and 4b reacted with the cinnamic acid-like fragments (5a–i) to afford target compounds I(a–i)−II(a–i) in 14–53% yields [7]. Their structures were characterized by HRMS, melting points, IR, and 1H NMR. Notably, the steric structure of 4a (CCDC: 2214110) was further determined by X-ray diffraction (Figure 2). Obviously, configurations of the ester group at the C-3 position and the hydroxyl group at the C-7 position of 4a were all β.
Scheme 1.
Synthesis of target compounds I(a–i)−II(a–i).
Figure 2.
X-ray crystal structure of compound 4a.
3.2. Insecticidal Activities
The results of the insecticidal activity of I(a–i)–II(a–i) against M. separata treated at 1 mg/mL are shown in Table 1. Among them, the corrected final mortality rates (CFMRs) of 2a, Id, Ig, and IIg were 45.4%, 48.4%, 51.5%, and 46.8%, respectively, whereas the CFMR of the precursor 1 was only 21.2%; that is, the growth-inhibitory activity of compounds 2a, Id, Ig, and IIg was 2.1–2.4-fold that of cholesterol. Compared with 1, compounds 2a,b; 3a,b; and 4a,b showed better insecticidal activity, indicating that structural modifications at the C-3 and C-7 positions were necessary for insecticidal activity. Moreover, compounds 2a–4a (R1 = Ph) showed more promising insecticidal activity than the corresponding ones 2b–4b (R1 = 4-MePh) (e.g., 2a vs. 2b; 3a vs. 3b; 4a vs. 4b). To compounds Ia–Ii (R1 = Ph), the introduction of cinnamic acids containing the fluorine atom or CF3 on the hydroxyl group of compound 4a resulted in promising compounds. For example, the CFMRs of Id (R2 = H, R3 = 4-F) and Ig (R2 = H, R3 = 4-CF3) were 48.4% and 51.5%, respectively, and the CFMRs of compounds Ie (R2 = H, R3 = 4-Cl) and If (R2 = H, R3 = 4-Br) were the same as that of 4a. Although the CFMR of Ii (R2 = H, R3 = 4-OMe) was 42.4%, the CFMRs of Ia (R2R3 = 3,4-OCH2O-), Ib (R2R3 = 3,4-OCH2CH2O-), and Ih (R2 = H, R3 = 4-Me) were only 33.3%, 36.3%, and 30.3%, respectively. The same structure–activity relationships were also observed for compounds IIa–IIi (R1 = 4-MePh): for instance, the CFMRs of IId (R2 = H, R3 = 4-F) and IIg (R2 = H, R3 = 4-CF3) were 37.5% and 46.8%, respectively, whereas the CFMRs of IIa–c,e,f,h,i were 25.0–34.3%. This demonstrates that the introduction of the fluorine atom or CF3 on the para position of the phenyl of Ic and IIc was very important for the insecticidal activity against M. separata.
Table 1.
Insecticidal activity of compounds I(a–i)–II(a–i) against M. separata at 1 mg/mL.
| Compound | Corrected Final Mortality Rate (Mean ± SE, %) a |
|---|---|
| 1 | 21.2 ± 2.7 |
| 2a | 45.4 ± 4.8 |
| 2b | 28.1 ± 2.7 |
| 3a | 42.4 ± 2.7 |
| 3b | 31.2 ± 2.7 |
| 4a | 39.3 ± 2.7 |
| 4b | 34.3 ± 4.8 |
| Ia | 33.3 ± 2.7 |
| Ib | 36.3 ± 4.8 |
| Ic | 27.2 ± 4.8 |
| Id | 48.4 ± 2.7 |
| Ie | 39.3 ± 2.7 |
| If | 39.3 ± 2.7 |
| Ig | 51.5 ± 2.7 |
| Ih | 30.3 ± 2.7 |
| Ii | 42.4 ± 2.7 |
| IIa | 25.0 ± 4.8 |
| IIb | 31.2 ± 2.7 |
| IIc | 28.1 ± 2.7 |
| IId | 37.5 ± 5.5 |
| IIe | 25.0 ± 4.8 |
| IIf | 34.3 ± 4.8 |
| IIg | 46.8 ± 2.7 |
| IIh | 31.2 ± 2.7 |
| IIi | 28.1 ± 2.7 |
| rotenone | 87.8 ± 2.7 |
a Values are mean ± SE of three replicates.
The results of the insecticidal activity of I(a–i)–II(a–i) against P. xylostella treated at 1 mg/mL are shown in Table 2. Among them, the CFMRs of Ig, IIf, and IIi were 40.9%, 44.1%, and 41.8%, respectively, whereas the CFMR of the precursor 1 was only 18.6%. Similarly, compounds 2a–4a (R1 = Ph) showed better insecticidal activity against P. xylostella than the corresponding ones 2b–4b (R1 = 4-MePh); for compounds Ia–Ii (R1 = Ph), the introduction of cinnamic acids containing the fluorine atom or CF3 on the hydroxyl group of compound 4a can result in the promising compounds Id (R2 = H, R3 = 4-F) and Ig (R2 = H, R3 = 4-CF3). However, for IIa–IIi (R1 = 4-MePh), compounds IIf (R2 = H, R3 = 4-Br) and IIi (R2 = H, R3 = 4-OMe) showed potent insecticidal activity against P. xylostella.
Table 2.
The insecticidal activity of compounds I(a–i)–II(a–i) against P. xyllostella at 1 mg/mL.
| Compound | Corrected Mortality Rate (Mean ± SE, %) a | |
|---|---|---|
| 24 h | 48 h | |
| 1 | 6.8 ± 2.2 | 18.6 ± 2.2 |
| 2a | 13.6 ± 2.2 | 23.2 ± 0 |
| 2b | 15.5 ± 2.2 | 20.4 ± 2.2 |
| 3a | 15.9 ± 2.2 | 25.5 ± 2.2 |
| 3b | 11.1 ± 2.2 | 22.7 ± 2.2 |
| 4a | 22.2 ± 2.2 | 29.5 ± 2.2 |
| 4b | 17.7 ± 2.2 | 25.0 ± 3.8 |
| Ia | 22.2 ± 2.2 | 31.8 ± 3.8 |
| Ib | 11.1 ± 2.2 | 25.0 ± 3.8 |
| Ic | 13.3 ± 0 | 22.7 ± 2.2 |
| Id | 24.4 ± 2.2 | 38.6 ± 3.8 |
| Ie | 8.9 ± 2.2 | 29.5 ± 2.2 |
| If | 20.0 ± 0 | 36.3 ± 2.2 |
| Ig | 26.6 ± 3.8 | 40.9 ± 2.2 |
| Ih | 15.5 ± 2.2 | 27.2 ± 2.2 |
| Ii | 17.7 ± 2.2 | 34.0 ± 2.2 |
| IIa | 15.9 ± 2.2 | 27.9 ± 2.2 |
| IIb | 20.0 ± 3.8 | 36.3 ± 2.2 |
| IIc | 13.3 ± 3.8 | 20.4 ± 2.2 |
| IId | 15.9 ± 2.2 | 25.5 ± 2.2 |
| IIe | 22.2 ± 2.2 | 34.0 ± 2.2 |
| IIf | 25.0 ± 3.8 | 44.1 ± 3.8 |
| IIg | 20.4 ± 2.2 | 34.8 ± 4.4 |
| IIh | 11.3 ± 0 | 18.6 ± 2.2 |
| IIi | 20.4 ± 2.2 | 41.8 ± 2.2 |
| β-cypermethrin | 56.8 ± 2.2 | 97.6 ± 2.2 |
a Values are mean ± SE of three replicates.
As described in Table 3, three potent compounds, Ig, IIf, and IIi, were further evaluated against P. xylostella, and their LC50 values were 1.560, 1.390, and 1.508 mg/mL, respectively. Namely, compared with that of their precursor 1 (LC50: 2.946 mg/mL), they exhibited 1.9–2.1-fold more potent insecticidal activity.
Table 3.
LC50 values at 48 h of compounds 1, Ig, IIf, and IIi against P. xyllostella a.
| Compound | Linear Regression Equation | LC50 (mg/mL) | Confidence Interval 95% (mg/mL) | r |
|---|---|---|---|---|
| 1 | Y = −0.816 + 1.738 X | 2.946 | 2.293–3.923 | 0.992 |
| Ig | Y = −0.253 + 1.308 X | 1.560 | 1.136–2.329 | 0.989 |
| IIf | Y = –0.201 + 1.405 X | 1.390 | 1.021–1.982 | 0.997 |
| IIi | Y = −0.239 + 1.339 X | 1.508 | 1.095–2.232 | 0.998 |
| β-cypermethrin | Y = 1.583 + 2.054 X | 0.170 | 0.132–0.211 | 0.989 |
a Values are mean ± SE of three replicates.
4. Conclusions
In summary, to develop new natural product-based pesticide candidates, a series of new cholesterol ester derivatives containing cinnamic acid-like fragments at the C-7 position were prepared. Against M. separata, compounds 2a, Id, Ig, and IIg showed 2.1–2.4 times more potent growth-inhibitory activity than cholesterol. Against P. xylostella, compounds Ig, IIf, and IIi exhibited 1.9–2.1 times more promising insecticidal activity than cholesterol. The structure–activity relationships of the compounds suggest that the introduction of the fluorine atom or CF3 on the para position of the phenyl of Ic and IIc was very important for the insecticidal activity against M. separata; and against P. xylostella, the introduction of the fluorine atom or CF3 on the para position of the phenyl of Ic was necessary for insecticidal activity, whereas the introduction of the bromine atom or methoxy on the para position of the phenyl of IIc was vital for insecticidal activity. These results will provide a basis for guiding the synthesis of novel cholesterol derivatives as new pesticidal agents in the future.
Acknowledgments
We thank Hongli Zhang for his finishing 1H NMR spectra.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/molecules27238437/s1, 1H NMR spectra.
Author Contributions
Formal analysis, H.W.; Investigation, Z.W.; Resources, S.Z.; Data curation, R.L. and J.X.; Project administration, H.X.; Funding acquisition, M.L. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
Sample Availability
Samples of the compounds are available from the authors.
Funding Statement
This research was funded by the National Natural Science Foundation of China (No. 31872013).
Footnotes
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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