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Article

Insecticidal Activity of Cyanohydrin and Monoterpenoid Compounds

1
Department of Entomology, Iowa State University, Ames, IA 50011 USA
2
Agriculture Canada, Vineland, ON, Canada
3
Department of Biochemistry, University of Wisconsin - Madison, Madison, WI 53706 USA
*
Author to whom correspondence should be addressed.
Molecules 2000, 5(4), 648-654; https://doi.org/10.3390/50400648
Submission received: 29 February 2000 / Accepted: 24 March 2000 / Published: 3 April 2000

Abstract

:
The insecticidal activities of several cyanohydrins, cyanohydrin esters and monoterpenoid esters (including three monoterpenoid esters of a cyanohydrin) were evaluated. Topical toxicity to Musca domestica L. adults was examined, and testing of many compounds at 100 μg/fly resulted in 100% mortality. Topical LD50 values of four compounds for M. domestica were calculated. Testing of many of the reported compounds to brine shrimp (Artemia franciscana Kellog) resulted in 100% mortality at 10 ppm, and two compounds caused 100% mortality at 1 ppm. Aquatic LC50 values were calculated for five compounds for larvae of the yellow fever mosquito (Aedes aegypti (L.)). Monoterpenoid esters were among the most toxic compounds tested in topical and aquatic bioassays.

Introduction

There is a growing need for effective, biodegradable pest-control compounds. Nineteen new major pesticides were introduced from 1961 to 1970, eight from 1971 to 1980, and only three from 1981 to 1985 [1]. Several recent publications from our laboratory have reported insect activity in cyanohydrin [2] and monoterpenoid compounds [3,4,5]. Naturally occurring cyanohydrins from flax, cassava, bamboo, peach pits and almonds probably serve a chemical defense function in the plants to protect against insect herbivory [6]. Hundreds of monoterpenoids are produced in plant essential oils, and apparently serve a defensive function as well [7]. In the current work we report the synthesis and biological activities of several new simple cyanohydrins, as well as novel cyanohydrin esters and monoterpenoid esters. Three compounds were monoterpenoid esters of a potent synthetic cyanohydrin, 1-cyano-1-hydroxy-2-propene (1; synonyms: CHP, 2-hydroxy-3-butenenitrile, acrolein cyanohydrin). CHP is an analog of two naturally occurring cyanohydrins in flax. These three cyanohydrins, CHP, methyl ethyl ketone cyanohydrin and dimethyl ketone cyanohydrin, have been shown to be potent insect fumigants [2]. We examined the activity in topical application to adult house flies (Musca domestica L.), as well as in aquatic bioassay to brine shrimp (Artemia franciscana Kellog) and the larvae of the yellow fever mosquito (Aedes aegypti (L.)).

Results and Discussion

The cyanohydrins synthesized by the methods reported in this study and tested against the invertebrates are shown in Figure 1.
Figure 2 shows the structures of cyanohydrin esters synthesized by the reported methods. Note that compounds 12, 13 and 15 are monoterpenoid esters of the cyanohydrin CHP (1).
Figure 3 shows the structures of esters of two monoterpenoids, cinnamic acid and cironellic acid.
Topical testing on M. domestica showed that most of the cyanohydrins and their analogs had LD50 values between 10 and 100 μg/fly (Table 1). Monoterpenoid esters containing the alcoholic moieties CHP (12, 13 and 15), propargyl (20 and 24) and allyl (19 and 23), all three of which are unsaturated, were the most effective. The presence of the CHP moiety was not always associated with high toxicity, and esterification of CHP with acetate, propionate or pivalate moieties produced less effective compounds than esterification of CHP with monoterpenoid moieties (compare 79 to 12, 13 and 15 in Table 1). More studies need to be conducted in order to determine the nature of toxicity in relation to structure.
The three cyanohydrin-monoterpenoid esters were among the most toxic compounds tested, with CHP citronellate (13) being the most toxic, showing 91% mortality at 10 μg/fly. CHP decanoate (12), CHP cinnamate (15), allyl cinnamate (19) and propargyl cinnamate (20) showed appreciable mortality at 10 μg/fly as well. Topical LD50 values on M. domestica (95% fiducial limit) were calculated by using SAS [8] and are reported in Table 2.
Aquatic testing with A. franciscana resulted in 100% mortality at 100 ppm for nearly all compounds tested (Table 3).
Several compounds showed 100% mortality at 10 ppm, and two compounds, propyl citronellate (22) and allyl citronellate (23), displayed 100% mortality at 1 ppm. The most toxic compounds tested on A. franciscana were esters of cinnamic acid or citronellic acid. Esterification of CHP with monoterpenoid moieties produced more effective compounds than esterification with the smaller moieties (compare 12, 13 and 15 to 7 and 911 in Table 3). The cyanohydrins and cyanohydrin esters were of lower toxicity than monoterpenoid esters (1724), except for CHP citronellate (13) and CHP cinnamate (15).
Aquatic LC50 values (95% fiducial limit) for A. aegypti larvae were calculated by using SAS [8] and are reported in Table 4.
For all tests, it appeared that esterification of CHP (1) with a nonmonoterpenoid moiety resulted in equal or lower activity in relation to CHP itself, and this was possibly related to moiety size and polarity. This result was also seen in the comparison of mandelonitrile (4) to mandelonitrile acetate (16) in topical LD50 values for M. domestica. Esterification of CHP with a monoterpenoid moiety, however, resulted in equal or higher activity in relation to CHP in topical and aquatic testing. Only three CHP-monoterpenoid esters were tested in this study; therefore, any conclusions regarding comparative effectiveness due to the properties of the monoterpenoid moieties are speculative. It is possible that their hydrolysis in vivo results in two insecticidal moieties, CHP and a monoterpenoid acid.
The limited series presented here indicates that alcoholic moieties containing double or triple bonds may be more effective than saturated ones, as methyl and propyl monoterpenoid esters were less effective than CHP, allyl or propargyl esters. Monoterpenoid esters were in most cases more toxic than monoterpenoid cyanohydrins. Esterification of some monoterpenoids has been demonstrated previously to enhance insecticidal activity [4,5].

Experimental

The structures of compounds 16 are shown in Figure 1, and the numerical designations used in this paper are as follows: 1-cyano-1-hydroxy-2-propene (CHP) (1), citronellyl cyanohydrin (i. e., the cyanohydrin synthesized from citronellal) (2), citryl cyanohydrin (3), mandelonitrile (4), 4-hydroxy-mandelonitrile (5) and cinnamyl cyanohydrin (6).
Structures of cyanohydrin esters are shown in Figure 2, and are named as follows: CHP acetate (7), CHP propionate (8), CHP pivalate (9), CHP acrylate (10), CHP 3-chloropropionate (11), CHP decanoate (12), CHP citronellate (13), CHP 4-fluorobenzoate (14), CHP cinnamate (15) and mandelonitrile acetate (16).
Monoterpenoid esters tested are shown in Figure 3: methyl cinnamate (17), propyl cinnamate (18), allyl cinnamate (19), propargyl cinnamate (20), methyl citronellate (21), propyl citronellate (22), allylcitronellate (23) and propargyl citronellate (24).
Compounds 13 and 6 were synthesized from potassium cyanide and their corresponding aldehyde. Stoichiometric amounts of potassium cyanide, the reactant aldehyde and glacial acetic acid were required. Potassium cyanide (KCN) was added to anhydrous diethyl ether and stirred with a magnetic stir bar. The aldehyde corresponding to the desired cyanohydrin was added slowly to the reaction mixture. Glacial acetic acid was added, and the reaction proceeded until the reactant aldehyde was no longer detected by thin-layer chromatography. The ethereal reaction mixture was washed three times with a saturated aqueous NaHCO3 solution, and the aqueous portion was back-extracted with three volumes of diethyl ether and the water layer discarded. The diethyl ether was removed by rotary evaporation, and the product purified by using column chromotography as necessary. Compounds 4 and 5 were purchased from Sigma Chemical (St. Louis, MO, USA).
Cyanohydrin esters 811, 14 and 16 were synthesized from their corresponding cyanohydrins and acid chlorides, following the method of Rice and Coats [4]. A method more suitable for synthesizing esters from cyanohydrins and carboxylic acids, utilizing dimethylaminopyridine (DMAP) and dicyclo-hexylcarboxiimide (DCC), was used for esters 1213 and 15 [5]. This method was also used for the synthesis of monoterpenoid esters 1724. Compound 7 (also known as 2-acetoxy butenenitrile) was purchased from Aldrich Chemical (Milwaukee, WI, USA).
Topical bioassays to M. domestica (Orlando regular strain) were conducted after Rice and Coats [4] using a 1-μl volume of acetone to deliver the chemical to the thoracic venters of house flies. The mosquito larvae (A. aegypti) and brine shrimp (A. franciscana) were tested by adding the chemical to water according to the method of Tsao et al. [9]. The mosquito larvae were provided by Dr. W. A. Rowley, Medical Entomology Laboratory at Iowa State University, Ames, IA. The brine shrimp were purchased from Carolina Biological Supply (Burlington, NC).

Acknowledgments

We thank the Program for Women in Science and Engineering at Iowa State University, Ames, IA. We also thank the Iowa Soybean Promotion Board for partial funding of this project. This is journal paper J-18803 of the Iowa Agriculture and Home Economics Experiment Station, Iowa State University, Ames, IA, project number 3187.

References and Notes

  1. Ku, H.S. Potential industrial applications of allelochemicals and their problems. In Allelochemicals: Role in Agriculture and Forestry; ACS Symposium Series #330; American Chemical Society: Washington, DC, 1987; pp. 449–454. [Google Scholar]
  2. Peterson, C.J.; Tsao, R.; Coats, J.R. Naturally occurring cyanohydrins, analogues and derivatives as potential fumigants. Pest Management Science. (in press).
  3. Lee, S.; Tsao, R.; Coats, J.R. Influence of dietary applied monoterpenoids and derivatives on survival and growth of the European corn borer (Lepidoptera: Pyralidae). J. Econ. Entomol. 1999, 92, 56–67. [Google Scholar] [CrossRef]
  4. Rice, P.J.; Coats, J.R. Insecticidal properties of monoterpenoid derivatives to the house fly (Diptera: Muscidae) and the red flour beetle (Coleoptera: Tenebrionidae). Pestic. Sci. 1994, 41, 195–202. [Google Scholar] [CrossRef]
  5. Tsao, R.; Lee, S.; Rice, P.J.; Jensen, C.; Coats, J.R. Monoterpenoids and their synthetic derivatives as leads for new insect-control agents. In Synthesis and Chemistry of Agrochemicals IV; Feynes, J.G., Basarab, G.S., Eds.; ACS Symposium Series; American Chemical Society: Washington, DC, 1995; pp. 312–324. [Google Scholar]
  6. Tewe, O.O.; Iyayi, E.A. Cyanogenic glycosides. In Toxicants of Plant Origin, vol. II; Cheeke, P.R., Ed.; CRC Press: Boca Raton, FL, 1989; pp. 43–60. [Google Scholar]
  7. Wise, M.L.; Croteau, R. Monoterpene biosynthesis. In Comprehensive Natural Products Chemistry, Vol. 2; Barton, D., Nakanishi, K., Meth-Cohn, O., Eds.; Elsevier: Amsterdam, 1999; pp. 97–153. [Google Scholar]
  8. SAS Institute. Ultrix SAS, Version 6.09 SAS User’s Guide; SAS Institute: Cary, NC, 1991. [Google Scholar]
  9. Tsao, R.; Reuber, M.; Johnson, L.; Coats, J.R. Insecticidal toxicities of glucosinolate–containing extracts from crambe seeds. J. Agric. Entomol. 1996, 13, 109–120. [Google Scholar]
  • Samples Availability: Available from the authors.
Figure 1. Structures of cyanohydrin compounds tested in this study.
Figure 1. Structures of cyanohydrin compounds tested in this study.
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Figure 2. Structures of cyanohydrin esters.
Figure 2. Structures of cyanohydrin esters.
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Figure 3. Monoterpenoid esters.
Figure 3. Monoterpenoid esters.
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Table 1. Results of topical toxicity testing on M. domestica (percentage mortality).
Table 1. Results of topical toxicity testing on M. domestica (percentage mortality).
Compound100 μg/fly10 μg/fly1 μg/fly
1CHP10005
7CHP acetate10000
8CHP propionate10000
9CHP pivalate8000
12CHP decanoate100640
13CHP citronellate100910
15CHP cinnamate87500
17Methyl cinnamate50010
18Propyl cinnamate3800
19Allyl cinnamate100404
20Propargyl cinnamate100350
21Methyl citronellate5754
22Propyl citronellate4100
23Allyl citronellate100175
24Propargyl citronellate100150
Control (acetone blank)0
Table 2. Topical LD50 values to Musca domestica (expressed in μg/fly) and 95% fiducial limits.
Table 2. Topical LD50 values to Musca domestica (expressed in μg/fly) and 95% fiducial limits.
CompoundLD5095% FL
2Citronellyl cyanohydrin> 50
3Citryl cyanohydrin> 50
4Mandelonitrile7.065.45, 8.54
54-Hydroxy mandelonitrile33.125.5, 47.5
6Cinnamyl cyanohydrin12.710.2, 15.7
16Mandelonitrile acetate14.511.8, 17.8
Table 3. Results of acute (24-hr) toxicity testing on Artemia franciscana (percentage mortality).
Table 3. Results of acute (24-hr) toxicity testing on Artemia franciscana (percentage mortality).
Compound100 ppm10 ppm1 ppm
1CHP1006320
3Citryl cyanohydrin8700
6Cinnamyl cyanohydrin1001525
7CHP acetate000
9CHP pivalate1003023
10CHP acrylate1004330
11CHP chloropropionate1004333
12CHP decanoate1009515
13CHP citronellate10010040
14CHP 4-fluorobenzoate202713
15CHP cinnamate10010095
17Methyl cinnamate1008035
18Propyl cinnamate10010065
19Allyl cinnamate10010095
20Propargyl cinnamate10010090
21Methyl citronellate10010045
22Propyl citronellate100100100
23Allyl citronellate100100100
24Propargyl citronellate1006425
Control4
Table 4. LD50 values (expressed in ppm) to Aedes aegypti larvae and 95% fiducial limits.
Table 4. LD50 values (expressed in ppm) to Aedes aegypti larvae and 95% fiducial limits.
CompoundLC5095% FL
1CHP2.751.94, 3.80
9CHP pivalate8.224.59, 17.8
10CHP acrylate5.193.55, 7.72
11CHP chloropropionate14.09.68, 23.9
14CHP 4-fluorobenzoate3.771.78, 7.78

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MDPI and ACS Style

Peterson, C.J.; Tsao, R.; Eggler, A.L.; Coats, J.R. Insecticidal Activity of Cyanohydrin and Monoterpenoid Compounds. Molecules 2000, 5, 648-654. https://doi.org/10.3390/50400648

AMA Style

Peterson CJ, Tsao R, Eggler AL, Coats JR. Insecticidal Activity of Cyanohydrin and Monoterpenoid Compounds. Molecules. 2000; 5(4):648-654. https://doi.org/10.3390/50400648

Chicago/Turabian Style

Peterson, Chris J., Rong Tsao, Aimee L. Eggler, and Joel R. Coats. 2000. "Insecticidal Activity of Cyanohydrin and Monoterpenoid Compounds" Molecules 5, no. 4: 648-654. https://doi.org/10.3390/50400648

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