10-Oxime and Their

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Semisynthesis of Esters of Fraxinellone C4/10-Oxime and Their Pesticidal Activities Qin Li, Xiaobo Huang, Shaochen Li, Jingchun Ma, Min Lv, and Hui Xu J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b01995 • Publication Date (Web): 24 Jun 2016 Downloaded from http://pubs.acs.org on June 26, 2016

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Journal of Agricultural and Food Chemistry

Semisynthesis of Esters of Fraxinellone C4/10-Oxime and Their Pesticidal Activities

Qin Li†, Xiaobo Huang†, Shaochen Li†, Jingchun Ma†, Min Lv*, †, and Hui Xu*, †,‡

†

College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi Province,

China. ‡

Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F

University, Yangling 712100, Shaanxi Province, China.

*M. Lv, Tel: 8629-8709-1952. Fax: 8629-8709-1952. E-mail: [email protected]. *H. Xu, Tel: 8629-8709-1952. Fax: 8629-8709-1952. E-mail: [email protected].

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ACS Paragon Plus Environment


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Abstract

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Twenty esters of fraxinellone C4/10-oxime were synthesized and determined by melting

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points, optical rotation, infrared spectra, proton nuclear magnetic resonance spectra, and

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high-resolution mass spectra. Two steric configurations of 7i and 8i were unambiguously

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confirmed by X-ray crystallography. Additionally, their pesticidal activities were assessed on

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two typical lepidopteran pests, Mythimna separata Walker and Plutella xylostella Linnaeus.

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Generally, all compounds exhibited less potent oral toxicity than toosendanin against

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3rd-instar larvae of P. xylostella. However, all compounds showed the growth inhibitory

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property against early 3rd-instar larvae of M. separata. Notably, compounds 7m, 8b, 8k, 9

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and 11 displayed more potent pesticidal activity than toosendanin. This demonstrated that

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introducing the C-4 carbonyl or oxime group on the fraxinellone resulted in more promising

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derivatives than those bearing a C-10 carbonyl or oxime substituent.

13 14 15 16 17 18 19 20

KEYWORDS: fraxinellone, structural modification, pesticidal activity, natural products-based

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insecticide, Mythimna separata Walker, Plutella xylostella Linnaeus

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INTRODUCTION

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Mythimna separata Walker (Oriental armyworm; Lepidoptera: Noctuidae) and Plutella

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xylostella Linnaeus (diamondback moth; Lepidoptera: Plutellidae) are two typical

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lepidopteran insect pests and hard to control. The infestation of these two insect pests very

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easily occurs, mainly because they have developed multiple resistances to commonly used

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conventional agrochemicals resulting in population outbreaks, affecting yields of maize,

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wheat, rice and some crucifer crops.1-7 Consequently, the search for new potential alternatives

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to effectively and selectively control insect pests has recently received considerable attention

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in the agricultural field.8-18

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Fraxinellone, 1 (Figure 1), a degraded limonoid, exhibited interesting pesticidal

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activities.19-21 To improve the agrochemical activities of compound 1, structural modification

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at its C-4 or C-10 position (A ring) was carried out in our group. Twenty-two compounds of

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fraxinellone-based esters,22 2 and 3, and hydrazones,23 4 and 5 (Figure 1) displayed higher

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pesticidal activities against early 3rd-instar larvae of M. separata than toosendanin. More

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recently, nine esters of obacunone C7-oxime, 6 (Figure 1) at 1 mg/mL have exhibited

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promising pesticidal activities against early 3rd-instar larvae of M. separata with the final

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mortality rates (FMRs) greater than 60%.24 Based upon the above results, here we

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synthesized two series of new fraxinellone derivatives, 7 and 8 (Figure 1) by introducing the

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C4/10 oxime ester moiety on compound 1 as pesticidal agents against M. separata and P.

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xylostella.

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MATERIALS AND METHODS

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Chemicals. Hydroxylamine hydrochloride and t-butyl hydroperoxide (t-BuOOH) were

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obtained from Aladdin Chemical Industrial Inc. (Shanghai, China). Ethyl acetate, petroleum 3



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ether, pyridine, dichloromethane, absolute ethanol, and 1,4-dioxane were obtained from Bodi

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Chemical Industrial Inc. (Tianjin, China). Sodium carbonate (Na2CO3), selenium dioxide

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(SeO2), anhydrous sodium sulfate (Na2SO4), and sodium hydrogen sulfite (NaHSO3) were

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obtained from Kelong Industrial Inc. (Chengdu, China). Fraxinellone (1) was extracted and

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obtained from Dictamnus dasycarpus.22 Two intermediates, fraxinellonone, 9 (30% yield) and

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3-formyl fraxinellone, 10 (27% yield) (Figure 2) were prepared as previously.22

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Instruments. Melting point (mp) was determined using the XT-4 digital melting point

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apparatus (Beijing Tech Instrument Ltd., Beijing, China). Optical rotation was measured

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using an Autopol III automatic polarimeter (Rudolph Research Analytical, NJ). Infrared (IR)

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spectra were measured by a TENSOR 27 spectrometer (Bruker, Ettlingen, Germany). Proton

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nuclear magnetic resonance spectra (1H NMR) were carried out with the Avance III 500 MHz

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equipment (Bruker, Karlsruhe, Germany). High-resolution mass spectra (HRMS) were

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carried out with LTQ FT Ultra instrument (Thermo Fisher Scientific Inc., MA). X-ray

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crystallography was recorded on a SMART APEX II equipment (Bruker, Karlsruhe,

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Germany).

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Synthesis of Fraxinellone C4-Oxime, 11, and Fraxinellone C10-Oxime, 12. A mixture of

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hydroxylamine hydrochloride (1.5 mmol), compound 9 or 10 (0.5 mmol) and pyridine (0.5

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mL) in 10 mL of C2H5OH was stirred at 80 oC. After 7 h, the reaction was complete, and

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ethanol was removed. To the residue, 15 mL of saturated aq. sodium bicarbonate was added.

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Then, the mixture was extracted with 30 mL of ethyl acetate three times. After dried over

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anhydrous Na2SO4, the solution was concentrated and purified by column chromatography

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(200-300 mesh silica gel) eluting with ethyl acetate/petroleum ether (v/v = 1/3) to afford

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compound 11 (89% yield) or 12 (91% yield) as a white solid. 4


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Data for 11: Mp 150–152 oC; [α] 20D 15 (c 2.5, CHCl3); IR cm-1 (KBr): 3439, 3153, 2931,

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1731, 1644, 1224, 1032, 982; 1H NMR (500 MHz, CDCl3) δ: 8.59 (s, 1H, -OH), 7.49 (s, 1H,

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H-2′), 7.46 (s, 1H, H-5′), 6.36 (s, 1H, H-4′), 5.02 (s, 1H, H-8), 3.14–3.19 (m, 1H, H-5),

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2.30–2.42 (m, 4H, H-5, 10), 1.92–1.96 (m, 1H, H-6), 1.69–1.75 (m, 1H, H-6), 0.91 (s, 3H,

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H-11); HRMS (ESI): Calcd for C14H16O4N ([M+H]+), 262.1074; Found, 262.1074.

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Data for 12: Mp 122–124 oC; [α]20D -34 (c 3.4, CHCl3); IR cm-1 (KBr): 3318, 3154, 3006,

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2924, 1757, 1648, 1271, 1045, 940; 1H NMR (500 MHz, CDCl3) δ: 8.99 (s, 1H, H-10), 7.49

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(s, 1H, H-2′), 7.46 (s, 1H, H-5′), 6.36 (s, 1H, H-4′), 5.00 (s, 1H, H-8), 2.67 (dd, J = 19.5, 6.0

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Hz, 1H, H-4), 2.38–2.45 (m, 1H, H-4), 1.94–1.98 (m, 1H, H-5), 1.84–1.87 (m, 1H, H-6),

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1.71–1.80 (m, 1H, H-5), 1.50–1.56 (m, 1H, H-6), 0.95 (s, 3H, H-11); HRMS (ESI): Calcd for

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C14H16O4N ([M+H]+), 262.1074; Found, 262.1074.

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General Procedure for Preparation of Esters of Fraxinellone C4/10-Oxime (7a–n and

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8a,b,e,f,i,k). A mixture of compound 11 or 12 (0.15 mmol), N,N′-dicyclohexylcarbodiimide

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(DCC, 0.18 mmol), corresponding carboxylic acids RCO2H (0.18 mmol), and

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4-dimethylaminopyridine (DMAP, 0.03 mmol) in 5 mL of dry CH2Cl2 was stirred at room

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temperature. After 3-20 h, 20 mL of CH2Cl2 was added to the mixture, which was washed

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successively with 15 mL of H2O, 15 mL of 0.1 M aq. HCl, 15 mL of 5% aq. Na2CO3, and 15

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mL of brine. After dried over anhydrous Na2SO4, the solution was concentrated and purified

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by

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dichloromethane/petroleum ether) to produce compounds 7a–n and 8a,b,e,f,i,k in 81–95%

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yields. Exemplary data for 7a–d and 8a,b,e are as follows:

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Data for 7a: Yield: 86%, white solid, mp 134–136 oC; [α] 20D 26 (c 2.7, CHCl3); IR cm-1

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(KBr): 3119, 2930, 1757, 1654, 1225, 1073, 951; 1H NMR (500 MHz, CDCl3) δ: 7.50 (s, 1H,

PTLC

eluting

with

ethyl

acetate/petroleum

ether

5


(or

ethyl

acetate/


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H-2′), 7.47 (s, 1H, H-5′), 6.35 (s, 1H, H-4′), 5.03 (s, 1H, H-8), 3.16–3.21 (m, 1H, H-5),

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2.47–2.55 (m, 1H, H-5), 2.41 (s, 3H, H-10), 2.27 (s, 3H, -CH3), 1.92–1.96 (m, 1H, H-6),

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1.73–1.79 (m, 1H, H-6), 0.92 (s, 3H, H-11); HRMS (ESI): Calcd for C16H18O5N ([M+H]+),

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304.1179; Found, 304.1179.

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Data for 7b: Yield: 88%, white solid, mp 85–87 oC; [α] 20D 22 (c 2.1, CHCl3); IR cm-1 (KBr):

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3146, 2940, 1746, 1652, 1224, 1069, 995; 1H NMR (500 MHz, CDCl3) δ: 7.46–7.50 (m, 2H,

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H-2′, 5′), 6.35 (s, 1H, H-4′), 5.03 (s, 1H, H-8), 3.15-3.20 (m, 1H, H-5), 2.47–2.58 (m, 3H,

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H-5, -CH2CH3), 2.41 (s, 3H, H-10), 1.92–1.95 (m, 1H, H-6), 1.73–1.79 (m, 1H, H-6), 1.23 (t,

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J = 7.5 Hz, 3H, -CH2CH3), 0.92 (s, 3H, H-11); HRMS (ESI): Calcd for C17H20O5N ([M+H]+),

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318.1336; Found, 318.1336.

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Data for 7c: Yield: 90%, white solid, mp 94–96 oC; [α] 20D 17 (c 2.5, CHCl3); IR cm-1 (KBr):

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3148, 2939, 1765, 1651, 1222, 1077, 925; 1H NMR (500 MHz, CDCl3) δ: 7.47–7.50 (m, 2H,

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H-2′, 5′), 6.35 (s, 1H, H-4′), 5.03 (s, 1H, H-8), 3.15–3.20 (m, 1H, H-5), 2.47–2.54 (m, 3H,

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H-5, -CH2CH2CH3), 2.42 (s, 3H, H-10), 1.92–1.96 (m, 1H, H-6), 1.73–1.79 (m, 3H, H-6,

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-CH2CH2CH3), 1.00 (t, J = 7.5 Hz, 3H, -(CH2)2CH3), 0.92 (s, 3H, H-11).

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Data for 7d: Yield: 91%, white solid, mp 89–91 oC; [α] 20D 16 (c 3.2, CHCl3); IR cm-1 (KBr):

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3137, 2968, 1745, 1654, 1224, 1084, 954; 1H NMR (500 MHz, CDCl3) δ: 7.47–7.50 (m, 2H,

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H-2′, H-5′), 6.35 (s, 1H, H-4′), 5.03 (s, 1H, H-8), 3.14–3.20 (m, 1H, H-5), 2.47–2.54 (m, 3H,

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H-5, -CH2(CH2)2CH3), 2.42 (s, 3H, H-10), 1.92–1.96 (m, 1H, H-6), 1.68–1.79 (m, 3H, H-6,

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-CH2CH2CH2CH3), 1.39–1.44 (m, 2H, -(CH2)2CH2CH3), 0.93 (t, J = 7.5 Hz, 3H, -(CH2)3CH3),

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0.92 (s, 3H, H-11); HRMS (ESI): Calcd for C19H24O5N ([M+H]+), 346.1649; Found,

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346.1646.

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Data for 8a: Yield: 93%, white solid, mp 103–105 oC; [α]20D -13 (c 2.8, CHCl3); IR cm-1 6


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(KBr): 3034, 2959, 2874, 1765, 1650, 1200, 1050, 942; 1H NMR (500 MHz, CDCl3) δ: 9.20

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(s, 1H, H-10), 7.50 (s, 1H, H-2′), 7.47 (s, 1H, H-5′), 6.36 (s, 1H, H-4′), 5.04 (s, 1H, H-8), 2.83

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(dd, J = 20.0, 6.5 Hz, 1H, H-4), 2.50–2.58 (m, 1H, H-4), 2.20 (s, 3H, -CH3), 1.96–2.00 (m,

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1H, H-5), 1.86–1.90 (m, 1H, H-6), 1.72–1.82 (m, 1H, H-5), 1.51–1.57 (m, 1H, H-6), 0.97 (s,

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3H, H-11); HRMS (ESI): Calcd for C16H18O5N ([M+H]+), 304.1179; Found, 304.1180.

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Data for 8b: Yield: 93%, white solid, mp 101–103 oC; [α] 20D -19 (c 3.3, CHCl3); IR cm-1

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(KBr): 3151, 3071, 2956, 1729, 1653, 1286, 1070, 965; 1H NMR (500 MHz, CDCl3) δ: 9.19

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(s, 1H, H-10), 7.46–7.49 (m, 2H, H-2′, 5′), 6.36 (s, 1H, H-4′), 5.02 (s, 1H, H-8), 2.83 (dd, J =

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20.5, 6.5 Hz, 1H, H-4), 2.51–2.59 (m, 1H, H-4), 2.44 (q, J = 7.5 Hz, 2H, -CH2CH3),

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1.95–2.00 (m, 1H, H-5), 1.86–1.89 (m, 1H, H-6), 1.74–1.82 (m, 1H, H-5), 1.51–1.57 (m, 1H,

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H-6), 1.21 (t, J = 7.5 Hz, 3H, -CH2CH3), 0.97 (s, 3H, H-11); HRMS (ESI): Calcd for

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C17H20O5N ([M+H]+), 318.1336; Found, 318.1336.

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Data for 8e: Yield: 90%, white solid, mp 168–170 oC; [α]20D -13 (c 2.3, CHCl3); IR cm-1

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(KBr): 3145, 3031, 2959, 1745, 1656, 1267, 1086, 963, 763, 711; 1H NMR (500 MHz, CDCl3)

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δ: 9.40 (s, 1H, H-10), 8.11–8.12 (m, 2H, Ph-H), 7.60–7.63 (m, 1H, Ph-H), 7.47–7.51 (m, 4H,

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H-2′, 5′, Ph-H), 6.37 (s, 1H, H-4′), 5.06 (s, 1H, H-8), 2.92 (dd, J = 20.0, 6.0 Hz, 1H, H-4),

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2.60–2.68 (m, 1H, H-4), 1.99–2.04 (m, 1H, H-5), 1.88–1.92 (m, 1H, H-6), 1.76–1.85 (m, 1H,

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H-5), 1.54–1.60 (m, 1H, H-6), 0.99 (s, 3H, H-11); HRMS (ESI): Calcd for C21H20O5N

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([M+H]+), 366.1336; Found, 366.1333.

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Biological Assay.

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Oral Toxicity of 1; 7a–n; 8a,b,e,f,i,k; and 9–12 against Plutella xylostella.25 Thirty

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3rd-instar larvae of P. xylostella were selected to each compound. Solutions of 1; 7a–n;

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8a,b,e,f,i,k; 9–12; and toosendanin (a positive control) were prepared in acetone at 20 mg/mL. 7



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The corresponding solution (1µL) was added to a fresh wheat leaf disc (0.5×0.5 cm), and

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dried (a blank control group (CK): only treated by acetone). One piece of the above discs was

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offered to and consumed by each insect, which was raised in each well of 12- or 24-well

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culture plates for 48 h (temperature: 25 ± 2 °C; relative humidity (RH): 65–80%; photoperiod:

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light/dark (L/D) = 16/8 h). Their corrected mortality rate values were calculated as follows:

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corrected mortality rate (%) = (T − C) × 100/ (100% − C); C is the mortality rate of CK, and T

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is the mortality rate of the treated P. xylostella.

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Growth Inhibitory Activity of 1; 7a–n; 8a,b,e,f,i,k; and 9–12 against Mythimna

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separata.26 Thirty early 3rd-instar larvae of M. separata were selected to each compound.

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Solutions of 1; 7a–n; 8a,b,e,f,i,k; 9–12; and toosendanin (a positive control) were prepared in

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acetone at 1 mg/mL. After dipped into the corresponding solution for 3 s, wheat leaf discs

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(1×1 cm) were taken out, and dried (a blank control group (CK): only treated by acetone).

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Several above discs were added to each culture dish (ten insects per dish). Once the discs

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were consumed, additional ones were added. After 48 h, the rest of compound-soaked discs

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was cleaned out, and the untreated ones were added till the end of pupae (temperature: 25 ±

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2 °C; RH: 65–80%; photoperiod: L/D = 12/12 h). Their corrected mortality rate values were

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calculated as follows: corrected mortality rate (%) = (T − C) × 100/ (100% − C); C is the

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mortality rate of CK, and T is the mortality rate of the treated M. separata.

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RESULTS AND DISCUSSION

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Synthesis. Fraxinellonone (9) and 3-formyl fraxinellone (10) were firstly obtained as

158

described previously (Figure 2).22 Then, hydroxylamine hydrochloride reacting with

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compounds 9 or 10 afforded fraxinellone C4-oxime (11) or fraxinellone C10-oxime (12).

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Finally, twenty esters of fraxinellone C4/10-oxime (7a–n and 8a,b,e,f,i,k) were obtained by 8


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reaction of different carboxylic acids with compounds 11 and 12, respectively. Their

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structures were determined by melting points, optical rotation, infrared spectra, proton

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nuclear magnetic resonance spectra, and high-resolution mass spectra. In addition, the E

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configuration of trisubstituted C=N of 7i and 8i was confirmed by means of X-ray

165

crystallography (Figures 3 and 4). Crystallographic data (excluding structure factors) of 7i

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and 8i were deposited at the Cambridge Crystallographic Data Centre (CCDC) with

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deposition numbers of 1469445 and 1469434, respectively.

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Insecticidal Activities. The oral toxicity of compounds 1; 7a–n; 8a,b,e,f,i,k; and 9–12

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against P. xylostella treated at 20 µg/larvae is shown in Table 1. Among all derivatives, only

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compounds 8f and 12 had mortality rates of 40.0% and 43.3%, respectively, after 48 h. In

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general, all compounds exhibited less potent oral toxicity than toosendanin.

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The growth inhibitory activity of compounds 1; 7a–n; 8a,b,e,f,i,k; and 9–12 against M.

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separata treated at 1 mg/mL is outlined in Table 2. Among all derivatives, compounds 7h,m;

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8a,b,f,k; 9; and 11 showed higher pesticidal activity than toosendanin. Compounds 7m, 8b,

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8k, 9 and 11, especially, displayed the most potent pesticidal activity with FMRs about 70%;

176

for instance, FMRs of 7m, 8b, 8k, 9 and 11 were 73.3%, 70.0%, 70.0%, 73.3%, and 70.0%,

177

respectively. Times for 50% mortality of 7a,b,d,h,j,m; 8a,b,f,k; 9; and 11 were 31, 6, 32, 28,

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29, 16, 6, 11, 21, 15, 9, and 10 days, respectively; whereas the time for 50% mortality of 1

179

was 29 days (Figure 5). Obviously, after structural modifications of 1, the times for 50%

180

mortality of some derivatives were shortened when compared with that of 1. In particular, the

181

times for 50% mortality of 7b and 8a were shortened to 6 days. In addition, the times for

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different growth stages of M. separata treated with 1; 7a,b,d,h,j,m; 8a,b,f,k; 9; and 11 are

183

shown in Figure 6. It demonstrated that the times from the larvae to the adult in the treated 9



184

groups were prolonged (30–32 days vs 29 days for CK). The symptoms for the treated M.

185

separata during three stages were also found: (1) during the first 48 h, the dead larvae had

186

thin and wrinkled bodies at the larval stage (Figure 7); (2) during the pupation stage, some

187

malformed and dead pupae were present (Figure 8); during the adult emergence stage, some

188

moths have been malformed from eclosion (Figure 9). This suggested that fraxinellone

189

derivatives probably affected the insect molting hormone.

190

Introduction of the C-4 carbonyl or oxime group on the fraxinellone led to more

191

promising derivatives than those having a C-10 carbonyl or oxime substituent (FMRs: 9

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(73.3%) vs 10 (36.7%); 11 (70.0%) vs 12 (46.7%)). Moreover, the pesticidal activities of 10

193

and 12 were less potent than that of 1. To C4-oxime ester derivatives of fraxinellone (7a–n),

194

except 7m (containing the 4-fluorobenzoyl at its oxime fragment; FMR: 73.3%), no

195

compounds were more potent than their precursors 9 and 11. Interestingly, introducing the

196

acetyl, propionyl, 3-methylbenzoyl or 4-nitrobenzoyl on the oxime group of 12 produced

197

potent compounds 8a,b,f,k, FMRs of which were 66.7%, 70.0%, 66.7%, and 70.0%,

198

respectively. Finally, the percentages of FMRs at three different growth stages of compounds

199

1; 7a,b,d,h,j,m; 8a,b,f,k; 9; and 11 are shown in Table 3. More than half of FMRs for

200

compounds 1, 7a,b,d,h,j; 8a,b,f,k; 9; and 11 were at the larval stage; especially the

201

percentages of FMRs at the larval stage of 7b and 8a were equal to, or greater than 90%. This

202

results were different with those of 2′(2′,6′)-(di)chloropicropodophyllotoxins (more than half

203

of FMRs were generally at the pupation stage).26 On the other hand, the pesticidal activity of

204

esters of fraxinellone C4/10-oxime was usually less potent than that of fraxinellone-based

205

hydrazone derivatives;23 whereas in general their pesticidal activity was more pronounced

206

than that of C4/10-ester derivatives of fraxinellone.22 10


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In conclusion, twenty esters of fraxinellone C4/10-oxime were semi-synthesized from

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fraxinellone and determined by the spectra analysis. Two steric configurations of 7i and 8i

209

were confirmed by X-ray crystallography. Although all compounds exhibited less potent oral

210

toxicity against P. xylostella than toosendanin, they showed growth inhibitory activity against

211

M. separata, and the times from the larvae to the adult in the treated groups were all

212

prolonged. It suggested that fraxinellone derivatives perhaps affected the insect molting

213

hormone. Notably, compounds 7m, 8b, 8k, 9 and 11 displayed the most potent pesticidal

214

activity, and they could be used as the lead compounds for further chemical modifications.

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ASSOCIATED CONTENT

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Supporting Information

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The Supporting Information is available free of charge on the ACS Publications website at

218

DOI:

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compounds.

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AUTHOR INFORMATION

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Corresponding Authors

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*(M.L.) Phone/fax: +86-29-87091952. E-mail: [email protected].

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*(H.X.) Phone/fax: +86-29-87091952. E-mail: [email protected].

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Funding

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The present research was supported by Special Funds of Central Colleges Basic Scientific

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Research Operating Expenses (No. 2014YB091, 2452015096), and National Natural Science

227

Foundation of China (No. 31000862).

228

Notes

229

The authors declare no competing financial interest.

Data on 1H NMR, HRMS, optical rotation, IR, and melting points of target

11



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Figure Captions. Figure 1. Chemical structures of fraxinellone (1) and its derivatives (2-5, 7 and 8), and obacunone derivatives (6). Figure 2. Synthesis of esters of fraxinellone C4/10-oxime (7a-n and 8a,b,e,f,i,k). Figure 3. X-ray crystal structure of 7i. Figure 4. X-ray crystal structure of 8i. Figure 5. Times for 50% mortality of compounds 1; 7a,b,d,h,j,m; 8a,b,f,k; 9; and 11 against M. separata. Figure 6. Times for different developmental stages of M. separata treated with compounds 1; 7a,b,d,h,j,m; 8a,b,f,k; 9; and 11. Figure 7. Representative abnormal larvae of M. separata produced by compounds 12 (LQ-2), 8a (LQ-6), 8f (LQ-7), 9 (LQ-21), 11 (LQ-22), 7j (LQ-31), and 7g (LQ-32) at 1 mg/mL during the larval period (CK: blank control group). Figure 8. Representative malformed pupae of M. separata produced by compounds 8i (LQ-3), 8f (LQ-7), 7i (LQ-23), 7f (LQ-26), 7e (LQ-34), 7c (LQ-44), and 8k (LQ-46) at 1 mg/mL during the pupation period (CK: blank control group). Figure 9. Representative malformed moth of M. separata produced by compounds 10 (LQ-1), 12 (LQ-2), 8f (LQ-7), 7i (LQ-23), 7a (LQ-28), 7g (LQ-32), and 7k (LQ-39) at 1 mg/mL during the stage of adult emergence (CK: blank control group).

16


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Figure 1.

17



Figure 2.

18


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Figure 3.

19



Figure 4.

20


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Figure 5.

21



Larvae

From the first larva pupated to the last one

Pupae

From the first adult emergenced to the last one

Figure 6.

22


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Figure 7.

23



Figure 8.

24


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Figure 9.

.

25



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Table 1. Oral Toxicity of Compounds 1; 7a–n; 8a,b,e,f,i,k; and 9–12 Against P. xylostella Treated at 20 µg/Larvaea compound

a

corrected mortality rate (%) 24 h

48 h

1

13.3 ± 6.7

43.3 ± 3.3

9

0±0

16.7 ± 8.8

10

0±0

20.0 ± 5.8

11

3.3 ± 3.3

33.3 ± 8.8

12

13.3 ± 6.7

43.3 ± 8.8

7a

3.3 ± 3.3

30.0 ± 5.8

7b

6.7 ± 6.7

26.7 ± 3.3

7c

3.3 ± 3.3

10.0 ± 0

7d

0±0

26.7 ± 3.3

7e

3.3 ± 3.3

26.7 ± 3.3

7f

0±0

10.0 ± 0

7g

0±0

20.0 ± 0

7h

3.3 ± 3.3

20.0 ± 5.8

7i

0±0

13.3 ± 6.7

7j

10.0 ± 5.8

26.7 ± 3.3

7k

10.0 ± 5.8

33.3 ± 6.7

7l

6.7 ± 6.7

26.7 ± 8.8

7m

6.7 ± 3.3

23.3 ± 3.3

7n

6.7 ± 6.7

30.0 ± 5.8

8a

0±0

16.7 ± 3.3

8b

3.3 ± 3.3

16.7 ± 3.3

8e

13.3 ± 3.3

30.0 ± 0

8f

10.0 ± 5.8

40.0 ± 5.8

8i

3.3 ± 3.3

16.7 ± 3.3

8k

0±0

20.0 ± 5.8

toosendanin

0±0

50.0 ± 0

blank control

0±0

0±0

Values are the mean ± SD of three replicates.

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Table 2. Growth Inhibitory Activity of Compounds 1; 7a–n; 8a,b,e,f,i,k; and 9–12 Against M. separata on Leaves Treated with a Concentration of 1 mg/mLa compound

a

corrected mortality rate (%) 10 days

20 days

33 days

1

26.7 ± 3.3

33.3 ± 6.7

56.7 ± 3.3

9

50.0 ± 5.8

53.3 ± 3.3

73.3 ± 3.3

10

6.7 ± 3.3

13.3 ± 3.3

36.7 ± 3.3

11

50.0 ± 5.8

53.3 ± 6.7

70.0 ± 0

12

26.7 ± 8.8

36.7 ± 3.3

46.7 ± 6.7

7a

26.7 ± 8.8

33.3 ± 3.3

50.0 ± 5.8

7b

56.7 ± 6.7

56.7 ± 6.7

56.7 ± 6.7

7c

16.7 ± 3.3

30.0 ± 0

36.7 ± 3.3

7d

36.7 ± 6.7

40.0 ± 5.8

50.0 ± 5.8

7e

23.3 ± 3.3

36.7 ± 3.3

43.3 ± 3.3

7f

0±0

16.7 ± 6.7

40.0 ± 10.0

7g

30.0 ± 5.8

33.3 ± 3.3

36.7 ± 8.8

7h

40.0 ± 5.8

43.3 ± 3.3

60.0 ± 0

7i

3.3 ± 3.3

16.7 ± 6.7

26.7 ± 3.3

7j

40.0 ± 5.8

40.0 ± 0

56.7 ± 12.0

7k

16.7 ± 8.8

20.0 ± 5.8

46.7 ± 3.3

7l

3.3 ± 3.3

23.3 ± 3.3

46.7 ± 8.8

7m

33.3 ± 3.3

66.7 ± 3.3

73.3 ± 8.8

7n

43.3 ± 3.3

43.3 ± 3.3

46.7 ± 8.8

8a

60.0 ± 0

63.3 ± 6.7

66.7 ± 8.8

8b

46.7 ± 3.3

50.0 ± 5.8

70.0 ± 5.8

8e

0±0

6.7 ± 3.3

22.3 ± 3.3

8f

26.7 ± 3.3

46.7 ± 6.7

66.7 ± 6.7

8i

6.7 ± 3.3

26.7 ± 3.3

36.7 ± 3.3

8k

43.3 ± 6.7

63.3 ± 3.3

70.0 ± 0

toosendanin

26.7 ± 3.3

40.0 ± 5.8

56.7 ± 6.7

blank control

0±0

0±0

0±0

Values are the mean ± SD of three replicates.

‘

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Table 3. Final Mortality Rates of Compounds 1; 7a,b,d,h,j,m; 8a,b,f,k; 9; and 11 at Three Different Growth Stages of M. separata. compound 1 9 11 7a 7b 7d 7h 7j 7m 8a 8b 8f 8k toosendanin

percentage of final mortality rate at three different stages (%) larvae pupae adult 53.0 72.7 71.4 53.4 100.0 73.4 66.7 70.6 45.4 90.0 71.4 55.0 71.4 53.0

23.5 9.1 9.6 26.6 0 13.3 5.5 11.8 45.4 5.0 14.3 25.0 23.9 29.4

28


23.5 18.2 19.0 20.0 0 13.3 27.8 17.6 9.2 5.0 14.3 20.0 4.7 17.6

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TOC graphic

29


10-Oxime and Their

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