Fourth Generation Insecticides

14 Fourth Generation Insecticides W. S. BOWERS

Downloaded by UNIV OF MICHIGAN ANN ARBOR on October 24, 2014 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/bk-1977-0037.ch014

New York State Agricultural Experiment Station, Geneva, Ν. Y.

Following discovery of the insect juvenile hormones and their importance to insect development, agricultural scientists became excited about the possibility of using these hormones for insect control. The presence of the juvenile hormones (JH) throughout immature development and during adult l i f e was readily demonstrated by classical endocrinological techniques. It was soon shown that these hormones prevent precocious development during the larval and nymphal stages and that adult insects required JH in order to permit development of the ovaries. C. M. Williams (1) prepared the f i r s t active extract from the cecropia moth and showed that this extract prevented adult development when applied to insect pupae. Treated pupae molted into morphogenetic monsters and died. Treatment of other stages produced no ill effects. From these studies i t became clear that during the transformation of the immature insect into the adult (during the pupal stage) the juvenile hormones must be absent. This short developmental period is completely deranged when supplied with JH. Three juvenile hormones in Figure 1 were identified by Bowers et a l . (2), Roller et a l . (3), Meyer et a l . ( 4 ) , Judy et a l . ( 5 ) . Although the natural juvenile hormones soon proved to be too labile under f i e l d conditions, many analogs were prepared which in addition to increased s t a b i l i t y were much more active than the natural hormones, Bowers ( 6 ) , Pallos et al. (7), Slama et a l . ( 8 ) . Zoecon has registered one analog (9) for control of floodwater mosquitos and manure-breeding f l i e s . The overall utility of control of insects with JH, however, is limited to those insects which can be brought into contact with the hormones during their brief period of sensitivity ( i . e . pupal or last -stage nymph). Under most f i e l d conditions insects exist in all stages of development and all but the last developmental stages are unaffected by excess JH since these are stages which require JH. Taking a somewhat different view, we reasoned that since juvenile hormones are required throughout most of an insect's 271

In Pesticide Chemistry in the 20th Century; Plimmer, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.


Figure 2.

Induction of precocious metamorphosis in the cotton stainer Dysdercus cingulatus with Precocene II



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l i f e , a more g e n e r a l l y u s e f u l method of i n s e c t c o n t r o l would be by preventing the s e c r e t i o n o f these hormones. Thus, a hormone antagonist should stop immature development and cause the i n s e c t to molt prematurely to an a d u l t . Likewise, an adult i n s e c t without j u v e n i l e hormone could not develop i t s ovaries and would be sterile. C e r t a i n adult i n s e c t s r e q u i r e JH f o r the production o f sex pheromones and might be rendered u n a t t r a c t i v e by a hormone antagonist. Insect diapause i n c e r t a i n l a r v a e (10) i s caused by an excess of JH, while adult diapause r e s u l t s from a lack o f JH (11, 12). I n t e r f e r i n g with the presence or absence o f JH during these stages could be d i s a s t r o u s f o r i n s e c t s . Our strategy f o r an endocrinologie approach to i n s e c t c o n t r o l t h e r e f o r e was based upon the search f o r a n t i - j u v e n i l e hormones. JH analogs have been found i n plants (.13, 14) so i t seemed p o s s i b l e that anti-hormones might a l s o e x i s t i n p l a n t s . We began t o extract p l a n t s with apolar solvents and t e s t e d these e x t r a c t s by contact and fumigation against the cotton s t a i n e r , Dysdercus c i n g u l a t u s , and the milkweed bug, Oncopeltus f a s c i a t u s . Eventually we found that the e x t r a c t o f the bedding p l a n t , Ageratum houstonianum, contained two potent a n t i - j u v e n i l e hormones. By contact and fumigation the e x t r a c t induced milkweed bug and cotton s t a i n e r nymphs to molt to t i n y a d u l t s , s k i p p i n g one or more o f t h e i r immature stages. These miniature adults d i d not reproduce and q u i c k l y died (Figure 2). Treatment o f adult females prevented ovarian development o r , i f developed ovaries were present at the time of treatment, the ovaries were caused t o regress to the undeveloped s t a t e . We were unable to induce precocious metamorphosis i n other i n s e c t Orders, but could s t e r i l i z e many of the adult stages by treatment with the e x t r a c t . I s o l a t i o n and i d e n t i f i c a t i o n o f the two n a t u r a l a n t i j u v e n i l e hormones revealed two simple chromenes; 7-methoxy-2,2dimethyl chromene and 6,7-dimethoxy-2,2-dimethyl chromene (Figure 3). Since these compounds induced precocious metamorphosis, we c a l l e d them Precocene I and II r e s p e c t i v e l y . Subsequently we found that both compounds had been p r e v i o u s l y i d e n t i f i e d and synthesized (JJ5, 16_, 17). We developed an e f f i c i e n t synthesis f o r these compounds^ shown i n Figure 4. In a d d i t i o n a l b i o l o g i c a l work we found that v i r g i n female American cockroaches, P e r i p l a n e t a americana, stopped producing t h e i r sex a t t r a c t a n t f o l l o w i n g treatment with Precocene I I , while milkweed bug and Mexican bean b e e t l e eggs t r e a t e d with Precocene II were unable to hatch. Normal non-diapausing Colorado potato b e e t l e s t r e a t e d with Precocene II promptly l e f t t h e i r food p l a n t s , burrowed i n t o the s o i l and entered diapause. A l l of these b i o l o g i c a l e f f e c t s o f the precocenes i n d i c a t e d that the s e c r e t i o n o f the j u v e n i l e hormones had been prevented. We t e s t e d t h i s hypothesis by t r e a t i n g i n s e c t s with both Precocene II and j u v e n i l e hormone. We found t h a t , when these compounds



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Precocene Figure 3.

/0

Precocene I I

I

Anti-juvenile hormones from Ageratum houstoni-

anum

PH

R

R = H,-OMe Figure 4. Synthesis of precocene. Reaction of an appropriate phenol with dimethyl acrylic acid and polyphosphoric acid (PPA) on the steam bath gives the chromanone in quantitative yield. Reduction with lithium aluminum hydride (LAH) and brief treatment with 4N hydrochloriic acid gives the chromene.



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were combined, milkweed bug nymphs developed normally, adult i n s e c t s developed t h e i r ovaries s u c c e s s f u l l y and produced v i a b l e eggs. Thus, the e f f e c t s o f the precocenes are f u l l y r e v e r s i b l e and confirm our hypothesis that they are a c t i n g to prevent the s e c r e t i o n o f the j u v e n i l e hormones. As p r e v i o u s l y s t a t e d , these compounds do not show a n t i j u v e n i l e hormone a c t i v i t y against a l l i n s e c t s , but open the door to a new mode o f i n s e c t c o n t r o l which a f f e c t s most i n s e c t stages and provides a broader dimension t o the e n d o c r i n o l o g i e s t r a t e g y of i n s e c t c o n t r o l . I f the j u v e n i l e hormones and t h e i r analogs are representa t i v e o f t h i r d - g e n e r a t i o n p e s t i c i d e s ( 1 8 ) , the a n t i - j u v e n i l e hormones may be considered i n a fourth-generation concept.

Literature Cited (1) Williams, C. Μ., Nature (1956) 178, 212. (2) Bowers, W. S., Thompson, M. J., Uebel, E. C . , Life Science (1965) 4, 2323. (3) R o l l e r , H. K . , Dahm, H., Sweeley, C. C . , Trost, Β. Μ., Angew. Chem. (1967) 79, 190. (4) Meyer, A. S., Schneiderman, Η. Α., Hanzman, Ε . , Ko, J . Η., Proc. N a t l . Acad. S c i . U. S. (1968) 60, 853. (5) Judy, K. J., Schooley, D. Α., Dunham, L. L . , H a l l , M. S., Bergot, B. J., S i d d a l l , J . B . , Proc. Natl. Acad. S c i . U. S. (1973) 70, 1509. (6) Bowers, W. S., Science (1969) 164, 323. (7) Pallos, F. Μ., Menn, J. J., Letchworth, P. Ε . , Miaullis,J.Β., Nature (1971) 232, 486. (8) Slama, Κ., Romanuk, Μ., Sorm, F . , "Insect Hormones and Bio -analogues" 477 pp., Springer Verlag, New York, 1974. (9) Hendrick, C. Α., S t a a l , G. B . , S i d d a l l , J . Β., J . Agr. Food Chem. (1973) 21, 354. (10) Chippendale, G. Μ., Y i n , C. Μ., Nature (1973) 246, 511. (11) de Wilde, J., De Boer, J . Α., J . Insect Physiol. (1961) 6, 152. (12) Bowers, W. S., Blickenstaff, C. C . , Science (1966) 154, 1673. (13) Bowers, W. S., Fales, Η. Μ., Thompson, M. J., Uebel, E. C . , Science (1966) 154, 1020. (14) Cerny, V., D i l e j s , L . , Labler, L . , Sorm, F . , Slama, Κ., Collect. Czech. Chem. Commun. (1967) 32, 3926. (15) Alertson, A. R., Acta. Chem. Scand. (1955) 9, 1725. (16) Huls, R., B u l l . Soc. Chim. Belg. (1958) 67, 22. (17) Livingstone, R., Watson, R. Β . , J . Chem. Soc. (1957) 1509. (18) Williams, C. M . , S c i . Amer. (1967) 217, (1) 13.


Fourth Generation Insecticides

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