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. 2017 Sep 20;2(9):5974–5980. doi: 10.1021/acsomega.7b01106

Application of Sustainable Natural Bioresources in Agriculture: Iodine-Mediated Oxidative Cyclization for Metal-Free One-Pot Synthesis of N-Phenylpyrazole Sarisan Analogues as Insecticidal Agents

Lailiang Qu †, Hongyu Xu ‡, Xiaoguang Wang †, Mengxing Huang †, Li Deng †, Yong Guo †,*
PMCID: PMC6044580  PMID: 30023758

Abstract

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In view of potential agricultural activity of sarisan (isolated from many plants or easily synthesized from sesamol, another biorenewable natural product) analogues, many research studies on the application of these biorenewable and abundant natural resources have been proceeded. A series of novel sarisan analogues containing N-phenylpyrazole were synthesized and evaluated for their insecticidal activity against a crop-threatening insect pest, Mythimna separata Walker. Meanwhile, an iodine-mediated oxidative intramolecular C–N bond formation methodology has been established for the one-pot synthesis of these N-phenylpyrazole-containing sarisan analogues. This practical one-pot methodology is metal-free and requires no separation of the less stable intermediate hydrazones. In addition, it was found that compounds 8l–r exhibited more promising insecticidal activity with the final mortality rates (FMRs) >62.1%, when compared with the positive control toosendanin. Especially, compound 8r with 2-fluoro-4-bromophenyl showed the most potent insecticidal activity, the FMR of which was 79.3%. On the basis of this, some interesting results of structure–activity relationships were also discussed.

1. Introduction

Mythimna separata Walker (oriental armyworm), also known as the Northern armyworm, is a typical crop-threatening pest, which is mainly distributed in China, India, Korea, and also other countries.1,2 The larvae of this insect pest can cause a great deal of damage to many cereal crops such as wheat, maize, and rice during its seasonal outbreaks.3,4 Although lots of synthetic chemical pesticides have been used to control insect pest outbreaks and also have played a crucial role in modern agriculture, the overuse and abuse of synthetic chemical pesticides over the years lead to considerable concern for pest resistance, pesticide residue, and other side effects on human health.5−7 Thus, there are urgent needs to discover new promising alternatives from the sustainable natural bioresources to effectively and selectively control the insect pest.

Sarisan (I, Figure 1), possessing a piperonyl moiety, is a biorenewable manoligan and isolated from many species of plants, such as Ligusticum mutellina,8Piper solmsianum C. DC,9Piper sarmentosum,10Saururus chinensis,11 and Beilschmiedia miersii.12 Its isomer, myristicin (II, Figure 1), is a well-known synergist for carbamates, pyrethroids, and other pesticides, of which synergistic activity is similar to commercial synergist piperonyl butoxide12,13 (V, Figure 1). Sarisan also shows a variety of biological activities including antimicrobial activity,8 anti-septic activity,12 and psychopharmacologic effect,14 especially its pesticidal activity against armyworms15 and different kinds of mosquitoes.16 In addition, pyrazole derivatives are one of the most interesting class of N-heterocyclic compounds that have remarkable biological activities in the areas of both pharmacological and agricultural activities, such as anticancer,17,18 antitubercular,19 antimicrobial,20 analgesic,21 insecticidal,22 acaricidal,23 herbicidal activities,24 and so forth. The well-known fipronil (III, Figure 1) is a representative pesticide containing the N-phenylpyrazole moiety for control of insects on wheat, corn, and other cereal crops, which was exploited by Rhône-Poulenc Inc., in 1987 and showed prominent insecticidal activity.25 In 1996, Bayer CropScience AG discovered another well-known insecticide ethiprole (IV, Figure 1), which belongs to fipronil derivative.26 The difference between them is that only trifluoromethylsulfinyl of fipronil was substituted by ethylsulfinyl. What is more, as far as we know, little attention has been paid to the introduction of the active substructure N-phenylpyrazole at the active position (C-3, 6, 1′, 2′, or 3′ position) of sarisan. Inspired by these interesting results and also in prolongation of our research on the discovery of new biorenewable natural product-based pesticides, in this paper, we designed and took advantage of iodine as a mediator to smoothly synthesize a series of N-phenylpyrazole sarisan analogues by one-pot methodology. Besides, we have evaluated the insecticidal activity of all the title compounds against M. separata and discussed the structure–activity relationships (SARs).

Figure 1.

Figure 1

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Structures of sarisan (I) and its related compounds (II–V).

2. Results and Discussion

2.1. Synthesis

As shown in Scheme 1, compounds 2–4 and the key intermediate 3-formylsarisan (5) were acquired as per our reported procedures.27 We used sesamol as the starting material to synthesize sarisan analogues instead of utilizing sarisan separated from plants, which not only can save economic costs but also can protect plant resources. First, sesamol was reacted with allylbromide and K2CO3 to afford allyl ether 2 in 93% yield, followed by Claisen rearrangement to afford phenol 3. Second, compound 3 was reacted with SnCl4, paraformaldehyde, and 1,8-diazabicyclo[5.4.0]undec-7-ene to afford 4 in 58% yield, and then methylation of compound 4 with CH3I–K2CO3 in acetone smoothly afforded 3-formylsarisan (5) in 87% yield. Finally, compound 6 was prepared by the condensation of compound 5 with acetophenone in KOH/MeOH/H2O and subsequently reacted with the corresponding hydrazine hydrochlorides 7a–t in EtOH to afford the target N-phenylpyrazole sarisan analogues 8a–t via I2-mediated oxidative cyclization. The structures of all target compounds were characterized through 1H/13C NMR, infrared (IR) spectroscopy, and melting point (mp).

Scheme 1. Synthetic Route for the Preparation of N-Phenylpyrazole Sarisan Analogues 8a–t.

Scheme 1

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However, above all, considering the synthesis of compound 8a as the template (Table 1), the reaction conditions for the synthesis of N-phenylpyrazole sarisan analogues via I2-mediated oxidative cyclization and different solvents were investigated. Initially, we investigated the amount of iodine for the one-pot synthesis of 8a in EtOH at reflux. The results indicated that a mixture of 6 and 7a in the presence of molecular iodine (2.0 equiv) was the best reaction condition and gave 8a in 89% yield. To further optimize the reaction conditions, we screened two commonly used solvents [N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO)] and found that this reaction did not proceed well in DMF/DMSO at 80 °C in the presence of 2.0 equiv of I2. Especially, when DMSO was used as the solvent, only a very small amount of 8a was formed in 7% yield. With the optimal one-pot reaction conditions (1.0 equiv of 6, 2.0 equiv of 7a, and 2.0 equiv of iodine in ethanol at refluxing temperature) in hand, we continued to optimize the reaction conditions by using two-step condensation. At first, compound 6 was condensed with 7a in ethanol at reflux to form the intermediate hydrazone 6a. After the first-step condensation was complete, compound 6a was separated from the reaction system, redissolved in EtOH, treated with 2.0 equiv of I2, and then heated to reflux, which also provided the desired compound 8a in 75% yield. In addition, a plausible mechanism for the formation of these N-phenylpyrazole sarisan analogues 8a–t is proposed. As shown in Scheme 2, the oxidative iodination of hydrazone 6a–t produces iodide intermediates A–T. Subsequently, intermediates A′–T′ are formed via an SN2′-type cyclization of compounds A–T, with the formation of a new C–N bond. Finally, the deprotonation of compounds A′–T′ affords the target N-phenylpyrazole sarisan analogues 8a–t.

Table 1. Optimization of the Reaction Conditions for the Synthesis of Compound 8aa.

2.1.

entry substrates equiv of I2 solvent temp yield (%)b
1c 6 + 7a 1.0 EtOH reflux 69
2c 6 + 7a 1.5 EtOH reflux 73
3c 6 + 7a 2.0 EtOH reflux 89
4c 6 + 7a 2.5 EtOH reflux 70
5c 6 + 7a 2.0 DMF 80 °C 60
6c 6 + 7a 2.0 DMSO 80 °C 7
7d 7a 2.0 EtOH reflux 75
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a

Optimal reaction conditions (entry 3): 6 (0.4 mmol), 7a (0.8 mmol), I2 (0.8 mmol), EtOH, and reflux.

b

Isolated yields after silica gel column chromatography.

c

A reaction mixture of 6, 7a, and I2 in EtOH/DMF was directly heated to reflux.

d

First, a mixture of 6 and 7a in EtOH was stirred at reflux, and after the reaction was complete, 6a was separated from the reaction system and then redissolved in EtOH, treated with I2, and heated to reflux.

Scheme 2. Proposed Mechanism for the Formation of N-Phenylpyrazole Sarisan Analogues 8a–t.

Scheme 2

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2.2. Insecticidal Activity

As shown in Table 2, the insecticidal activity of compounds I and 8a–t against M. separata Walker was evaluated as the final mortality rates (FMRs) at 1 mg mL–1. Toosendanin, a commercial insecticide derived from Melia azedarach, was used as the positive control. We used corn leaves treated with acetone alone as a blank control. Among all the tested samples, compounds 8c and 8e showed equivalent insecticidal activity to the positive control toosendanin with the FMR = 51.7%, which was higher than the parent compound I with the FMR = 44.8%. Compounds 8b and 8l–r exhibited more potent insecticidal activity than toosendanin, and their FMRs were all higher than 51.7%. Especially, compound 8r showed excellent insecticidal activity with the FMR = 79.3%, which was 27.6% higher than that of toosendanin. In addition, we found that the corresponding FMRs of 33 days were generally higher than those of 20 and 10 days, which indicated that these title compounds showed delayed insecticidal activity.28 Administration of the target compounds to the larvae of M. separata resulted in an array of developmental abnormalities, affecting growth, molting, and metamorphosis. For example, as shown in Figure 2, because of feeding too much of compound-treated leaves within the first 48 h, some larvae died with the symptoms of blackened, wrinkled, and dehydrated bodies. This phenomenon may be due to the effects of the N-phenylpyrazole sarisan analogues on nutritional or digestive interference.29,30 In the second stage of pupation, many pupae could not molt into normal pupae and then died (Figure 3). Similarly, during the last stage of the emergence period, many malformed moths were observed with shrunk, short, or immature wings and dead toward the end (Figure 4). The appearance of these malformed pupae and moths suggested that these compounds might disrupt the endocrine control of molting.31,32 This experimental phenomenon was different from traditionally synthetic pesticides, such as organophosphates, organochlorine pesticides, and so forth, which often kill most of the insect pests within a few hours33 This symptom indicated that the effect of the title compounds could cause toxicity to the treated larvae as they suffered from ecdysial stasis and inhibition of development, resulting in the suppression of larval–pupal ecdysis and adult emergence. In this way, these N-phenylpyrazole sarisan analogues can affect reproduction, reducing egg production and disrupting endocrine system.34,35 On the other hand, to make further investigation of this phenomenon, we analyzed the percentages of FMRs of the representative compounds 8l–r and toosendanin at three different growth stages of M. separata (Figure 5). We found that more than half of dead M. separata due to compounds 8l–r and toosendanin were at the larval period. This result could further demonstrate that the administration of the target compounds to the treated insect pests mainly inhibit larval–pupal ecdysis, which resulted in the death of most of the insects during pupation.

Table 2. Insecticidal Activity of Compounds I and 8a–t against M. separata on Leaves Treated at a Concentration of 1 mg mL–1a.

  corrected mortality rate (±SD)
compound 10 days 20 days 33 days
sarisan (I) 13.3 (±3.3) 26.7 (±3.3) 44.8 (±3.3)
8a (QLL-105) 13.3 (±3.3) 33.3 (±3.3) 44.8 (±6.7)
8b (QLL-90) 30.0 (±5.8) 46.7 (±6.7) 55.2 (±3.3)
8c (QLL-89) 26.7 (±3.3) 46.7 (±3.3) 51.7 (±3.3)
8d (QLL-91) 16.7 (±3.3) 33.3 (±3.3) 44.8 (±3.3)
8e (QLL-88) 23.3 (±3.3) 40.0 (±5.8) 51.7 (±3.3)
8f (QLL-87) 16.7 (±3.3) 33.3 (±3.3) 44.8 (±3.3)
8g (QLL-81) 20.0 (±0) 33.3 (±3.3) 44.8 (±3.3)
8h (QLL-99) 16.7 (±3.3) 26.7 (±3.3) 34.5 (±3.3)
8i (QLL-93) 20.0 (±0) 33.3 (±3.3) 41.4 (±3.3)
8j (QLL-95) 23.3 (±3.3) 36.7 (±3.3) 44.8 (±3.3)
8k (QLL-96) 16.7 (±3.3) 30.0 (±0) 37.9 (±0)
8l (QLL-100) 30.0 (±0) 46.7 (±3.3) 65.5 (±3.3)
8m (QLL-101) 23.3 (±3.3) 43.3 (±3.3) 62.1 (±3.3)
8n (QLL-94) 26.7 (±3.3) 50.0 (±0) 69.0 (±5.8)
8o (QLL-102) 30.0 (±5.8) 46.7 (±3.3) 62.1 (±3.3)
8p (QLL-97) 36.7 (±3.3) 53.3 (±3.3) 65.5 (±3.3)
8q (QLL-98) 36.7 (±3.3) 46.7 (±3.3) 62.1 (±3.3)
8r (QLL-103) 46.7 (±3.3) 63.3 (±3.3) 79.3 (±0)
8s (QLL-104) 20.0 (±0) 33.3 (±3.3) 41.4 (±3.3)
8t (QLL-106) 23.3 (±3.3) 43.3 (±3.3) 48.3 (±5.8)
toosendanin 13.3 (±3.3) 40.0 (±0) 51.7 (±3.3)
blank control 0 (±0) 0 (±0) 3.3 (±3.3)
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a

Values are the mean ± SD of three replicates.

Figure 2.

Figure 2

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The representative abnormal larvae pictures of 8c (QLL-89), 8d (QLL-91), 8j (QLL-95), 8l (QLL-100), 8n (QLL-94), 8q (QLL-98), and 8r (QLL-103) during the larval period (CK: blank control group).

Figure 3.

Figure 3

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The representative malformed pupae pictures of 8b (QLL-90), 8d (QLL-91), 8e (QLL-88), 8j (QLL-95), 8l (QLL-100), 8n (QLL-94), and 8p (QLL-97) during the pupation period (CK: blank control group).

Figure 4.

Figure 4

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The representative malformed moth pictures of 8b (QLL-90), 8c (QLL-89), 8j (QLL-95), 8n (QLL-94), 8p (QLL-97), 8q (QLL-98), and 8r (QLL-103) during the emergence period (CK: blank control group).

Figure 5.

Figure 5

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The percentages of the FMRs of compounds 8l, 8m, 8n, 8o, 8p, 8q, and 8r and toosendanin during three different growth periods.

Finally, we also have discovered some interesting results of SARs of the tested compounds. The introduction of N-(fluorophenyl)pyrazole at the C-3 position of sarisan could lead to more potent compounds than those possessing chlorophenyl, bromophenyl, and electron-donating groups on the phenyl ring [e.g., FMRs: 8b (55.2%), 8e (51.7%) versus 8d (44.8%), 8f (44.8%), 8g (44.8%), 8h (34.5%), and 8k (37.9%)]. Interestingly, we found that the introduction of polyhalogenated phenylpyrazole at the C-3 position of sarisan could lead to more promising analogues than monohalogenated phenylpyrazole, except for compound 8t. For example, the FMRs of 8l (R = 3,4-difluorophenyl), 8m (R = 3,4-dichlorophenyl), 8n (R = 2,4-dichlorophenyl), 8o (R = 3,5-difluorophenyl), 8p (R = 2-chloro-4-fluorophenyl), 8q (R = 2-chloro-5-fluorophenyl), and 8r (R = 2-fluoro-4-bromophenyl) were all higher than 62.1%. Especially, the introduction of N-(2-fluoro-4-bromophenyl)pyrazole at the C-3 position of sarisan exhibited the most potent insecticidal activity.

3. Conclusions

In summary, a series of novel N-phenylpyrazole sarisan analogues were prepared and their insecticidal activities were evaluated against a crop-threatening agricultural insect pest, M. separata Walker. Among all the target compounds, compounds 8l–r exhibited more promising insecticidal activity with their FMRs higher than 62.1%, when compared with the positive control toosendanin. Especially, compound 8r with 2-fluoro-4-bromophenyl showed the most potent insecticidal activity, whose FMR was 79.3%. On the other hand, we have established an efficient methodology for the synthesis of N-phenylpyrazole sarisan analogues through iodine-mediated oxidative intramolecular C–N bond formation. This practical one-pot methodology is metal-free and requires no separation of the less stable intermediates hydrazones. Their SARs indicated that introduction of N-(fluorophenyl)pyrazole or polyhalogenated phenylpyrazole at the C-3 position of sarisan could lead to more potent compounds, especially introduction of N-(2-fluoro-4-bromo-phenyl)pyrazole. These promising results are of importance to the application of sarisan analogues as biorenewable pesticidal agents in crop protection.

4. Experimental Section

4.1. Instrument and Materials

Sesamol (99.0%) and different substituted phenylhydrazine hydrochlorides (95.0%) were obtained from Macklin Biochemical Inc. Analytical thin-layer chromatography (TLC) and preparative TLC (PTLC) were performed by silica gel plates using silica gel GF254 (Qingdao Haiyang Chemical Co., Ltd., Qingdao, China). Other reagents were of analytical grade and purchased from Innochem Co., Ltd. and KeLong Chemical Reagent Co., Ltd. Anhydrous solvents were purified and dried in terms of standard procedures. The mps were recorded on a digital mp instrument (Beijing Tech Instrument Co., Ltd.) and were uncorrected. IR spectra were detected as dry films (KBr) on a PE-1710 Fourier-transform-IR spectrometer (PerkinElmer, Waltham, MA, USA). The 1H/13C NMR data were recorded on a Bruker Avance (400/100 MHz) NMR spectrometer (Bruker, Bremerhaven, Germany) using CDCl3 as the solvent and tetramethylsilane as the internal standard. In addition, compounds 2–5 were prepared using the same method as our previous report.27

4.2. General Procedure for the Synthesis of Compound 6

A mixture of compound 5 (5 mmol, 1100.4 mg), acetophenone (7.5 mmol, 901.1 mg), and KOH (15 mmol, 841.5 mg) in MeOH/H2O (2:1 v/v) was stirred at 0–5 °C for 2 h. When the reaction was complete, the mixture was diluted with water (10 mL) and extracted with CH2Cl2 (20 mL × 3). The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified through silica gel column chromatography (petroleum ether/ethyl acetate, 8:1, v/v) to afford the desired ketone α,β-unsaturated 6.

4.2.1. Data for 6

Yellow solid: yield 99%; 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 7.2 Hz, 2H, −Ph), 7.88–7.98 (m, 2H, double bond), 7.56–7.60 (m, 1H, −Ph), 7.48 (t, J = 7.2 Hz, 2H, −Ph), 6.71 (s, 1H, H-6), 6.09 (s, 2H, −OCH2O−), 5.88–5.98 (m, 1H, H-2′), 5.06–5.10 (m, 2H, H-3′), 3.73 (s, 3H, −OCH3), 3.35 (d, J = 6.4 Hz, 2H, H-1′).

4.3. General Procedure for the Synthesis of Compound 6a

A mixture of compound 6 (0.4 mmol, 128.8 mg) and phenylhydrazine hydrochloride (0.8 mmol, 115.7 mg) in absolute ethanol (10 mL) was refluxed. After the reaction was complete depending on TLC analysis, the solvent was concentrated under reduced pressure. The residue was finally purified by PTLC to provide the intermediate 6a.

4.3.1. Data for 6a

White solid: yield 98%; 1H NMR (400 MHz, DMSO): δ 8.86 (s, 1H, −NH−), 7.53–7.63 (m, 3H, −Ph), 7.44 (d, J = 16.4 Hz, 1H, double bond), 7.31 (d, J = 6.8 Hz, 2H, −Ph), 7.17 (d, J = 4.0 Hz, 4H, −Ph), 6.74–6.78 (m, 1H, −Ph), 6.61 (s, 1H, H-6), 6.11 (d, J = 16.4 Hz, 1H, double bond), 6.10 (s, 2H, −OCH2O−), 5.82–5.92 (m, 1H, H-2′), 4.98–5.02 (m, 2H, H-3′), 3.38 (s, 3H, −OCH3), 3.20 (d, J = 6.4 Hz, 2H, H-1′). 13C NMR (100 MHz, DMSO): δ 149.2, 146.0, 144.7, 143.3, 143.3, 137.3, 134.3, 131.8, 129.3, 129.0, 128.5, 128.7, 124.8, 121.1, 119.4, 115.6, 113.9, 113.1, 107.8, 101.4, 61.3, 33.1.

4.4. General Procedure for the Synthesis of Compounds 8a–t

To a stirred solution of α,β-unsaturated ketone 6 (0.4 mmol, 128.8) and the corresponding hydrazine hydrochlorides (0.8 mmol, 115.7 mg) in ethanol was added molecular iodine (0.8 mmol, 203.0 mg), and then the reaction was heated to reflux under N2. When the reaction was complete according to TLC analysis, the solvent was concentrated, quenched with 5% Na2S2O3, and then extracted with ethyl acetate (20 mL × 3). The combined organic layer was dried over anhydrous sodium sulfate, concentrated, and purified through PTLC to afford the target compounds 8a–t. The example data of compounds 8a–e are listed as follows, whereas those of other compounds are depicted in the Supporting Information.

4.4.1. Data for 8a

Yellow liquid: yield 89%; IR cm–1 (KBr): 3065, 2932, 2896, 1599, 1499, 1457, 1399, 1207, 1051, 768, 693; 1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.2 Hz, 2H, −Ph), 7.40–7.44 (m, 4H, −Ph), 7.30–7.35 (m, 3H, −Ph), 7.23–7.27 (m, 1H, −Ph), 6.94 (s, 1H, H-6), 6.66 (s, 1H, H-4″), 5.82–5.92 (m, 1H, H-2′), 5.71 (s, 2H, −OCH2O−), 4.96–5.05 (m, 2H, H-3′), 3.44 (s, 3H, −OCH3), 3.27 (d, J = 6.4 Hz, 2H, H-1′); 13C NMR (100 MHz, CDCl3): δ 152.0, 149.9, 144.5, 143.4, 140.8, 137.0, 134.9, 133.0, 128.6, 128.6, 127.9, 127.0, 125.8, 123.4, 115.7, 110.0, 107.8, 106.8, 101.4, 61.2, 33.9.

4.4.2. Data for 8b

Yellow liquid: yield 61%; IR cm–1 (KBr): 3704, 2933, 2887, 1508, 1459, 1208, 1050, 764, 668; 1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 7.6 Hz, 2H, −Ph), 7.40–7.50 (m, 4H, −Ph), 7.29–7.35 (m, 1H, −Ph), 7.05–7.17 (m, 2H, −Ph), 7.00 (s, 1H, H-6), 6.62 (s, 1H, H-4″), 5.79–5.87 (m, 1H, H-2′), 5.67 (s, 2H, −OCH2O−), 4.90–5.01 (m, 2H, H-3′), 3.46 (s, 3H, −OCH3), 3.24 (d, J = 6.0 Hz, 2H, H-1′).

4.4.3. Data for 8c

Yellow liquid: yield 88%; IR cm–1 (KBr): 3063, 2931, 2899, 1492, 1456, 1207, 1121, 1048, 764, 694; 1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 7.6 Hz, 2H, −Ph), 7.38–7.43 (m, 4H, −Ph), 7.31–7.34 (m, 1H, −Ph), 7.20–7.28 (m, 2H, −Ph), 6.97 (s, 1H, H-6), 6.60 (s, 1H, H-4″), 5.73–5.83 (m, 3H, −OCH2O–, and H-2′), 4.94 (dd, J = 1.6, 10.0 Hz, 1H, H-3′), 4.82 (dd, J = 1.6, 17.6 Hz, 1H, H-3′), 3.47 (s, 3H, −OCH3), 3.19 (d, J = 6.4 Hz, 2H, H-1′).

4.4.4. Data for 8d

Yellow liquid: yield 82%; IR cm–1 (KBr): 3071, 2933, 2890, 1594, 1484, 1456, 1207, 1052, 766, 660; 1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 7.2 Hz, 2H, −Ph), 7.56 (s, 1H, −Ph), 7.41–7.45 (m, 2H, −Ph), 7.32–7.36 (m, 1H, −Ph), 7.20–7.26 (m, 3H, −Ph), 6.94 (s, 1H, H-6), 6.69 (s, 1H, H-4″), 5.83–5.93 (m, 1H, H-2′), 5.79 (s, 2H, −OCH2O−), 4.96–5.06 (m, 2H, H-3′), 3.42 (s, 3H, −OCH3), 3.27 (d, J = 6.4 Hz, 2H, H-1′).

4.4.5. Data for 8e

White solid: yield 67%; mp 63–65 °C; IR cm–1 (KBr): 3074, 2974, 2938, 2892, 1511, 1467, 1210, 1053, 851, 769, 693; 1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 7.2 Hz, 2H, −Ph), 7.37–7.44 (m, 4H, −Ph), 7.31–7.35 (m, 1H, −Ph), 6.98 (t, J = 8.4 Hz, 2H, −Ph), 6.93 (s, 1H, H-6), 6.67 (s, 1H, H-4″), 5.82–5.92 (m, 1H, H-2′), 5.76 (s, 2H, −OCH2O−), 4.95–5.05 (m, 2H, H-3′), 3.43 (s, 3H, −OCH3), 3.26 (d, J = 6.4 Hz, 2H, H-1′).

4.5. Biological Assay

The insecticidal activity of compounds I and 8a–t against M. separata was evaluated by the leaf-dipping method in line with the previously reported method.36,37 Thirty pre-third-instar larvae of the same size and level of health (10 larvae per group) were chosen as the tested pests for each compound. Acetone solutions of compounds I and 8a–t and toosendanin (used as a positive control) were prepared at the concentration of 1 mg mL–1. Fresh corn leaves were cut into leaf disks (1 × 1 cm2), dipped into the sample solution for 3 s, then taken out, and dried in RT. The larvae of tested groups were fed with compound-coated leaves, whereas the larvae of blank control group (CK) were fed with acetone-treated leaves alone. Several treated leaf disks were kept in each dish. Once the treated leaves were consumed, the corresponding ones were added to the dish. After 48 h, the larvae were treated with untreated fresh leaves and observed until the adult emergence (temperature: 25 ± 2 °C; relative humidity: 65–80%; and photoperiod: (light/dark) = 12/12 h). The corrected mortality rate values of the tested compounds were calculated by the following formula: corrected mortality rate (%) = (T – C) × 100/(1 – C), where T is the mortality rate of the tested samples and C is the mortality rate of CK.

Supporting Information Available

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.7b01106.

  • 1H/13C NMR, IR, and mp data for all the target compounds (PDF)

Author Contributions

These authors contributed equally to this work.

We would like to thank the National Natural Science Foundation of China (no. 21502176) and the China Postdoctoral Science Foundation (no. 2015M582207) for research funding.

The authors declare no competing financial interest.

Supplementary Material

ao7b01106_si_001.pdf (599.9KB, pdf)

References

  1. Xiao H.-J.; Fu X.-W.; Liu Y.-Q.; Wu K.-M. Synchronous vitellogenin expression and sexual maturation during migration are negatively correlated with juvenile hormone levels in Mythimna separata. Sci. Rep. 2016, 6, 33309. 10.1038/srep33309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Liu Z.; Wang X.; Lei C.; Zhu F. Sensory genes identification with head transcriptome of the migratory armyworm, Mythimna separata. Sci. Rep. 2017, 7, 46033. 10.1038/srep46033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Sharma H. C.; Sullivan D. J.; Bhatnagar V. S. Population dynamics and natural mortality factors of the Oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae), in South-Central India. Crop Prot. 2002, 21, 721–732. 10.1016/s0261-2194(02)00029-7. [DOI] [Google Scholar]
  4. Feng H.-Q.; Zhao X.-C.; Wu X.-F.; Wu B.; Wu K.-M.; Cheng D.-F.; Guo Y.-Y. Autumn migration of Mythimna separata (Lepidoptera: Noctuidae) over the Bohai Sea in northern China. Environ. Entomol. 2008, 37, 774–781. 10.1093/ee/37.3.774. [DOI] [PubMed] [Google Scholar]
  5. Köhler H.-R.; Triebskorn R. Wildlife ecotoxicology of pesticides: can we track effects to the population level and beyond?. Science 2013, 341, 759–765. 10.1126/science.1237591. [DOI] [PubMed] [Google Scholar]
  6. Heckel D. G. Insecticide resistance after silent spring. Science 2012, 337, 1612–1614. 10.1126/science.1226994. [DOI] [PubMed] [Google Scholar]
  7. Yadav I. C.; Devi N. L.; Syed J. H.; Cheng Z.; Li J.; Zhang G.; Jones K. C. Current status of persistent organic pesticides residues in air, water, and soil, and their possible effect on neighboring countries: a comprehensive review of India. Sci. Total Environ. 2015, 511, 123–137. 10.1016/j.scitotenv.2014.12.041. [DOI] [PubMed] [Google Scholar]
  8. Villegas M.; Vargas D.; Msonthi J. D.; Marston A.; Hostettmann K. Isolation of the antifungal compounds falcarindiol and sarisan from Heteromorpha trifoliata. Planta Med. 1988, 54, 36–37. 10.1055/s-2006-962326. [DOI] [PubMed] [Google Scholar]
  9. Bizzo H. R.; Lopes D.; Abdala R. V.; Pimentel F. A.; De Souza J. A.; Pereira M. V. G.; Bergter L.; Guimarães E. F. Sarisan from leaves of Piper affinis hispidinervum C. DC (long pepper). Flavour Fragrance J. 2001, 16, 113–115. 10.1002/ffj.957. [DOI] [Google Scholar]
  10. Masuda T.; Inazumi A.; Yamada Y.; Padolina W. G.; Kikuzaki H.; Nakatani N. Antimicrobial phenylpropanoids from Piper sarmentosum. Phytochemistry 1991, 30, 3227–3228. 10.1016/0031-9422(91)83180-s. [DOI] [Google Scholar]
  11. Seo C.-S.; Lee Y.-K.; Kim Y.-J.; Jung J.-S.; Jahng Y.; Chang H.-W.; Song D.-K.; Son J.-K. Protective Effect of Lignans against Sepsis from the Roots of Saururus chinensis. Biol. Pharm. Bull. 2008, 31, 523–526. 10.1248/bpb.31.523. [DOI] [PubMed] [Google Scholar]
  12. Kumamoto J.; Scora R. W. Structure of sarisan, an isomer of myristicin, isolated from the leaf oil of Beilschmiedia miersii. J. Agric. Food Chem. 1970, 18, 544–545. 10.1021/jf60169a006. [DOI] [Google Scholar]
  13. Majerus S. L.; Alibhai N.; Tripathy S.; Durst T. New syntheses of dillapiol [4,5-dimethoxy-6-(2-propenyl)-1,3-benzodioxole], its 4-methylthio and other analogs. Can. J. Chem. 2000, 78, 1345–1355. 10.1139/v00-138. [DOI] [Google Scholar]
  14. Moreira D. L.; Souza P. O.; Kaplan M. A. C.; Pereira N. A.; Cardoso G. L.; Guimarães E. F. An. Acad. Bras. Cienc. 2001, 73, 33–57. 10.1590/s0001-37652001000100004. [DOI] [PubMed] [Google Scholar]
  15. Passreiter C. M.; Akhtar Y.; Isman M. B. Insecticidal activity of the essential oil of Ligusticum mutellina roots. Z. Naturforsch., C: J. Biosci. 2005, 60, 411–414. 10.1515/znc-2005-5-608. [DOI] [PubMed] [Google Scholar]
  16. Arnason J. T.; Durst T.; Foster B.. Derivatives of dillapiol and related monolignans and use thereof. U.S. Patent 9,386,767, 2016.
  17. Dawood K. M.; Eldebss T. M. A.; El-Zahabi H. S. A.; Yousef M. H.; Metz P. Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents. Eur. J. Med. Chem. 2013, 70, 740–749. 10.1016/j.ejmech.2013.10.042. [DOI] [PubMed] [Google Scholar]
  18. Koca I.; Özgür A.; Coşkun K. A.; Tutar Y. Synthesis and anticancer activity of acyl thioureas bearing pyrazole moiety. Bioorg. Med. Chem. 2013, 21, 3859–3865. 10.1016/j.bmc.2013.04.021. [DOI] [PubMed] [Google Scholar]
  19. Pathak R. B.; Chovatia P. T.; Parekh H. H. Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Bioorg. Med. Chem. Lett. 2012, 22, 5129–5133. 10.1016/j.bmcl.2012.05.063. [DOI] [PubMed] [Google Scholar]
  20. Gouda M. A.; Berghot M. A.; El-Ghani G. E. A.; Khalil A. M. Synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4, 5, 6, 7-tetrahydrobenzothiophene moiety. Eur. J. Med. Chem. 2010, 45, 1338–1345. 10.1016/j.ejmech.2009.12.020. [DOI] [PubMed] [Google Scholar]
  21. Vijesh A. M.; Isloor A. M.; Shetty P.; Sundershan S.; Fun H. K. New pyrazole derivatives containing 1,2,4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents. Eur. J. Med. Chem. 2013, 62, 410–415. 10.1016/j.ejmech.2012.12.057. [DOI] [PubMed] [Google Scholar]
  22. Song H.; Liu Y.; Xiong L.; Li Y.; Yang N.; Wang Q. Design, synthesis, and insecticidal activity of novel pyrazole derivatives containing α-hydroxymethyl-N-benzyl carboxamide, α-chloromethyl-N-benzyl carboxamide, and 4,5-dihydrooxazole moieties. J. Agric. Food Chem. 2012, 60, 1470–1479. 10.1021/jf204778v. [DOI] [PubMed] [Google Scholar]
  23. Dai H.; Li G.; Chen J.; Shi Y.; Ge S.; Fan C.; He H. Synthesis and biological activities of novel 1,3,4-thiadiazole-containing pyrazole oxime derivatives. Bioorg. Med. Chem. Lett. 2016, 26, 3818–3821. 10.1016/j.bmcl.2016.04.094. [DOI] [PubMed] [Google Scholar]
  24. Waldrep T. W.; Beck J. R.; Lynch M. P.; Wright F. L. Synthesis and herbicidal activity of 1-aryl-5-halo and 1-aryl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamides. J. Agric. Food Chem. 1990, 38, 541–544. 10.1021/jf00092a045. [DOI] [Google Scholar]
  25. Tingle C. C. D.; Rother J. A.; Dewhurst C. F.; Lauer S.; King W. J.. Fipronil: environmental fate, ecotoxicology, and human health concerns. Reviews of Environmental Contamination and Toxicology; Springer: New York, 2003; pp 1–66. [DOI] [PubMed] [Google Scholar]
  26. Caboni P.; Sammelson R. E.; Casida J. E. Phenylpyrazole insecticide photochemistry, metabolism, and GABAergic action: ethiprole compared with fipronil. J. Agric. Food Chem. 2003, 51, 7055–7061. 10.1021/jf030439l. [DOI] [PubMed] [Google Scholar]
  27. Guo Y.; Qu L.; Wang X.; Huang M.; Jia L.; Zhang Y. Iodine-catalyzed oxidative cyclisation for the synthesis of sarisan analogues containing 1,3,4-oxadiazole as insecticidal agents. RSC Adv. 2016, 6, 93505–93510. 10.1039/c6ra22343e. [DOI] [Google Scholar]
  28. Xu H.Comments to, Insecticide resistance after silent spring, 2013, http://comments.sciencemag.org/content/10.1126/science.1226994.
  29. Kirkbride-Smith A. E.; Bell H. A.; Edwards J. P. Effects of three vertebrate hormones on the growth, development, and reproduction of the tomato moth, Lacanobia oleracea L. (Lepidoptera: Noctuidae). Environ. Toxicol. Chem. 2001, 20, 1838–1845. . [DOI] [PubMed] [Google Scholar]
  30. Henrick C. A.; Staal G. B.; Siddall J. B. Alkyl 3,7,11-trimethyl-2,4-dodecadienoates, a new class of potent insect growth regulators with juvenile hormone activity. J. Agric. Food Chem. 1973, 21, 354–359. 10.1021/jf60187a043. [DOI] [PubMed] [Google Scholar]
  31. Bengochea P.; Christiaens O.; Amor F.; Viñuela E.; Rougé P.; Medina P.; Smagghe G. Insect growth regulators as potential insecticides to control olive fruit fly (Bactrocera oleae Rossi): insect toxicity bioassays and molecular docking approach. Pest Manage. Sci. 2013, 69, 27–34. 10.1002/ps.3350. [DOI] [PubMed] [Google Scholar]
  32. Wang Q. L.; Liu T.-X. Effects of Three Insect Growth Regulators on Encarsia formosa (Hymenoptera: Aphelinidae), an Endoparasitoid of Bemisia tabaci (Hemiptera: Aleyrodidae). J. Econ. Entomol. 2016, 109, 2290–2297. 10.1093/jee/tow216. [DOI] [PubMed] [Google Scholar]
  33. Koh D.; Jeyaratnam J. Pesticides hazards in developing countries. Sci. Total Environ. 1996, 188, S78–S85. 10.1016/0048-9697(96)05279-5. [DOI] [PubMed] [Google Scholar]
  34. Dhadialla T. S.; Carlson G. R.; Le D. P. New insecticides with ecdysteroidal and juvenile hormone activity. Annu. Rev. Entomol. 1998, 43, 545–569. 10.1146/annurev.ento.43.1.545. [DOI] [PubMed] [Google Scholar]
  35. Wing K. D.; Slawecki R. A.; Carlson G. R. RH 5849, a nonsteroidal ecdysone agonist: effects on larval Lepidoptera. Science 1988, 241, 470–472. 10.1126/science.241.4864.470. [DOI] [PubMed] [Google Scholar]
  36. Guo Y.; Yan Y.; Yu X.; Wang Y.; Zhi X.-Y.; Hu Y.; Xu H. Synthesis and insecticidal activity of some novel fraxinellone-based esters. J. Agric. Food Chem. 2012, 60, 7016–7021. 10.1021/jf301734h. [DOI] [PubMed] [Google Scholar]
  37. Guo Y.; Qu H.; Zhi X.; Yu X.; Yang C.; Xu H. Semisynthesis and insecticidal activity of some fraxinellone derivatives modified in the B ring. J. Agric. Food Chem. 2013, 61, 11937–11944. 10.1021/jf404195m. [DOI] [PubMed] [Google Scholar]

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