Role of Natural Product Chemistry - ACS Symposium Series (ACS

23 Role of Natural Product Chemistry J. R.

PLIMMER

Agrochemicals and Residues Section, Joint

FAO/IAEA

Division, International A t o m i c Energy

Downloaded by UNIV OF PITTSBURGH on May 3, 2015 | http://pubs.acs.org Publication Date: April 26, 1985 | doi: 10.1021/bk-1985-0276.ch023

Agency, Vienna, Austria

The rapidly expanding growth of knowledge of natural product structures now provide clearer understanding of biochemical mechanisms. This has made possible "biorational" approaches to the design of pest control agents. Natural products may be of potential value in pest control in several ways. They may be a source of structures for screening. They may possess activity that is applicable to pest control directly or after structural modification of the original structure. Finally, the recognition of their function in nature may suggest new approaches to pest control. However, their practical application may be limited by economics. Resistant plants are important in managing insect pests and their resistance may arise from many factors. Some plants contain insecticidal principles that may be exploited. Compounds that modify insect behaviour are not directly lethal, but may be valuable in pest control. However, their efficacy may be difficult and costly to determine. During t h e l a t t e r h a l f o f t h e n i n e t e e n t h century and t h e e a r l y decades o f t h e t w e n t i e t h c e n t u r y , t h e groundwork o f s t r u c t u r a l o r g a n i c c h e m i s t r y was l a i d . I n 1828, t h e theory t h a t a " v i t a l f o r c e * was u t i l i z e d i n p l a n t s a n d a n i m a l s t o e l a b o r a t e n a t u r a l p r o d u c t s w a s d i s p r o v e d , when W o h l e r a n n o u n c e d t h a t u r e a c o u l d b e f o r m e d b y h e a t i n g ammonium c y a n a t e . The i n v e s t i g a t i o n o f t h e t h e o r e t i c a l basis o f organic chemistry received i t s stimulus not only from the contemporary s p i r i t o f p h i l o s o p h i c a l i n q u i r y , b u t a l s o from t h e p r o s p e c t s o f a p r a c t i c a l outcome. The i n d u s t r i a l r e v o l u t i o n had as i t s b a s i s t h e a v a i l a b i l i t y o f energy i n t h e form o f c o a l . C o a l g a s was u s e d f o r l i g h t i n g e a r l y i n t h e nineteenth century. C o a l t a r was r e c o g n i z e d a s a s o u r c e o f o r g a n i c c h e m i c a l s , a n d W.H. P e r k i n ' s d i s c o v e r y o f t h e f i r s t c o a l t a r d y e i n 1 8 5 6 o c c u r r e d when h e a t t e m p t e d p r e p a r a t i o n o f q u i n i n e by o x i d a t i o n o f a n i l i n e . Subsequently, s y n t h e t i c d y e s t u f f s r a p i d l y r e p l a c e d those from n a t u r a l sources. The a b i l i t y t o 1

0097-6156/ 85/0276-0323$06.00/0 © 1985 American Chemical Society

In Bioregulators for Pest Control; Hedin, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1985.

BIOREGULATORS FOR PEST CONTROL


324

produce a v a r i e t y o f s y n t h e t i c chemicals from c o a l t a r and subsequently from petroleum feedstocks has g r e a t l y i n f l u e n c e d t h e development o f t h e chemical i n d u s t r y . The p r e v a l e n c e o f s t r u c t u r a l t y p e s b a s e d o n a r o m a t i c o r h e t e r o a r o m a t i c n u c l e i among c h e m i c a l s a v a i l a b l e f r o m c o a l t a r o r petroleum contrasts with t h e s t r u c t u r a l types that represent t h e major groups o f n a t u r a l products. Chemicals from n a t u r a l sources are a r i c h source o f s t r u c t u r a l d i v e r s i t y and r e f l e c t t h e c o m p l e x i t y o f b i o l o g i c a l systems i n which t h e processes o f b i o s y n t h e s i s and t h e b i o l o g i c a l r o l e s o f m o l e c u l e s have undergone c o n t i n u a l change and m o d i f i c a t i o n . N a t u r a l product chemistry remains a c h a l l e n g i n g branch o f study. Progress i n both theory and p r a c t i c e o f o r g a n i c chemistry has h a s t e n e d t h e p r o c e s s o f e l u c i d a t i o n o f m o l e c u l a r s t r u c t u r e . The p a u c i t y o f s t a r t i n g m a t e r i a l a n d r e l a t i v e l y p r i m i t i v e t e c h n o l o g y h a d , i n some c a s e s , m e a n t t h a t a l m o s t a c e n t u r y was required t o establish details o f molecular structure. Molecules of even moderate c o m p l e x i t y p r e s e n t e d a major c h a l l e n g e u n t i l modern i n s t r u m e n t a l t e c h n i q u e s s i m p l i f i e d t h e problems o f s e p a r a t i o n , c h a r a c t e r i z a t i o n , and s t e r e o c h e m i s t r y . W i t h i n t h e l a s t t h r e e d e c a d e s , i t h a s become p o s s i b l e t o d e r i v e s t r u c t u r a l i n f o r m a t i o n f r o m a f e w nanograms o f m a t e r i a l and t h e e l u c i d a t i o n o f s t r u c t u r e a n d s y n t h e s i s o f b i o l o g i c a l p o l y m e r s h a s now become almost r o u t i n e . I n addition, a better understanding o f c o n f o r m a t i o n a l p r i n c i p l e s and t h e i n f l u e n c e o f s t e r e o c h e m i s t r y on r e a c t i v i t y o f m o l e c u l e s now c o n t r i b u t e s g r e a t l y t o r a p i d elucidation of structure. Biorational

Approaches

Such i n f o r m a t i o n has l e d t o e x p l o s i v e growth i n t h e u n d e r s t a n d i n g of biochemical processes. Knowledge o f metabolism, b i o s y n t h e t i c p r o c e s s e s , n e u r o c h e m i s t r y , r e g u l a t o r y m e c h a n i s m s , a n d many o t h e r aspects o f p l a n t , animal and i n s e c t b i o c h e m i s t r y has p r o v i d e d a b a s i s o n w h i c h t h e mode o f a c t i o n o f a p e s t i c i d e may o f t e n b e more c l e a r l y u n d e r s t o o d . The e x p l o i t a t i o n o f b i o l o g i c a l i n f o r m a t i o n c a n l e a d t o t h e s y n t h e s i s o f a new m o l e c u l e d e s i g n e d to act a t a p a r t i c u l a r s i t e o r block a key step i n a biochemical process. The p o t e n t i a l v a l u e o f t h i s a p p r o a c h h a s g e n e r a t e d increasing interest i nthefunctioning of insect neurosecretory systems. T h a t s e l e c t i v e c h e m i c a l c o n t r o l methods m i g h t emerge f r o m a n i n c r e a s e d u n d e r s t a n d i n g o f i n s e c t b i o c h e m i s t r y became apparent w i t h t h e d i s c o v e r y o f t h e i n s e c t j u v e n i l e hormones. I n v e s t i g a t i o n o f s e c r e t i o n s from the corpora a l l a t a l e d t o t h e i d e n t i f i c a t i o n o f i n s e c t j u v e n i l e hormones and p r o v i d e d a stimulus f o r t h e study o f the molecular b a s i s o f i n s e c t p h y s i o l o g y ( 1 , 2, 3 ) . J u v e n i l e hormone a n a l o g u e s a r e p r o v i n g very valuable f o r selective control o f insects. A potentially more a t t r a c t i v e method a p p e a r s t o be t h e u s e o f c h e m i c a l s t h a t w o u l d b l o c k j u v e n i l e hormone p r o d u c t i o n , b e c a u s e s u c h compounds would shorten t h e l i f e t i m e o f t h e l a r v a e , t h e l i f e stage o f t h e i n s e c t w h i c h i n f l i c t s m o s t damage o n t h e h o s t . Screening of


23.

PLIMMER

Role of Natural Product Chemistry


p l a n t e x t r a c t s l e d to the d i s c o v e r y t h a t precocenes (from the p l a n t A g e r a t u m h o u s t o n i a n i u m ) p o s s e s s e d t h i s p r o p e r t y (4), but t h e a c t i v i t y i s c o n s i d e r e d t o r e s u l t f r o m c y t o t o x i c i t y and d e g e n e r a t i o n o f t h e c o r p o r a a l l a t a (5, 6) and n o t f r o m s p e c i f i c interference with biosynthetic routes. I n v e s t i g a t i o n of the b i o s y n t h e t i c pathways i n v o l v e d i n the p r o d u c t i o n o f j u v e n i l e hormones (tetrahydro-4-fluoromethyl-4hydroxy-2H-pyran-2-one) i n the c o r p o r a a l l a t a r e v e a l e d the i n v o l v e m e n t o f m e v a l o n o l a c t o n e as an i n t e r m e d i a t e and l e d t o t h e s y n t h e s i s of p o t e n t i a l b l o c k i n g agents w i t h the subsequent d i s c o v e r y of the a c t i v i t y of fluoromeralonolactone as an i n h i b i t o r o f j u v e n i l e hormone b i o s y n t h e s i s (7). E x p l o i t a t i o n of t h e s e f i n d i n g s has c o n t i n u e d i n a s e a r c h f o r more p o t e n t compounds o f p r a c t i c a l v a l u e (8). Such d i s c o v e r i e s gave r i s e t o the term " b i o r a t i o n a l " to describe s y n t h e t i c i n s e c t i c i d e s t h a t a r e d e s i g n e d by c o n s i d e r a t i o n o f s p e c i f i c b i o c h e m i c a l targets. T h e s e d e v e l o p m e n t s i n d i c a t e p o t e n t i a l new modes o f s e l e c t i v e insecticidal action. Through a b e t t e r understanding of the p h y s i o l o g i c a l p r o c e s s e s , t h e b a s i s o f s c r e e n i n g c a n be b r o a d e n e d and t h e i n c r e a s e d k n o w l e d g e o f t h e d i v e r s e b i o c h e m i c a l pathways s u g g e s t s new a p p r o a c h e s t o t h e d e s i g n o f p e s t i c i d e s . Natural

Products

i n Pest

Control

The u t i l i z a t i o n o f n a t u r a l p r o d u c t s i n p e s t c o n t r o l may be c o n s i d e r e d f r o m a number o f s t a n d p o i n t s . F i r s t , the v a r i e t y of s t r u c t u r a l t y p e s p r o v i d e s a r i c h s o u r c e o f compounds o r m o d e l s f o r c o n v e n t i o n a l s c r e e n i n g programmes. Second, c o n s i d e r a t i o n of t h e known b i o l o g i c a l a c t i v i t y o f a n a t u r a l p r o d u c t may l e a d t o i t s a p p l i c a t i o n i n p e s t management, e i t h e r d i r e c t l y o r a f t e r structural modification. T h i r d , the r e c o g n i t i o n and u n d e r s t a n d i n g o f t h e f u n c t i o n o f a c h e m i c a l i n n a t u r e may reveal p o t e n t i a l a p p r o a c h e s t o p e s t management. F o r c o n t r o l o f some p e s t p r o b l e m s , m a t e r i a l s f r o m n a t u r a l s o u r c e s have p r o v e d e x t r e m e l y s u c c e s s f u l . I n p a r t i c u l a r , many p l a n t , human, a n d a n i m a l d i s e a s e s a r e c o n t r o l l e d b y a n t i b i o t i c s p r o d u c e d by m i c r o o r g a n i s m s . I n s e c t i c i d e s from p l a n t sources have b e e n u s e d e f f e c t i v e l y f o r many y e a r s , b u t t h e s c a l e on w h i c h t h e y have been u s e d does not compare w i t h t h a t of the s y n t h e t i c o r g a n i c i n s e c t i c i d e s i n t r o d u c e d i n t h e y e a r s f o l l o w i n g W o r l d War II. A p p l i c a t i o n of n a t u r a l products to pest c o n t r o l i s subject to s i m i l a r considerations to those that a f f e c t synthetic compounds. E l u c i d a t i o n o f s t r u c t u r e may be a r e l a t i v e l y r o u t i n e m a t t e r , b u t s y n t h e s i s may p r e s e n t d i f f i c u l t i e s , p a r t i c u l a r l y where t h e r e are s e v e r a l s t e r e o c h e m i c a l possibilities. There are o f t e n g r e a t d i f f e r e n c e s i n b i o l o g i c a l a c t i v i t y among d i f f e r e n t s t e r e o i s o m e r s and t h e p r e s e n c e o f i n a c t i v e i s o m e r s i n a p r o d u c t may be u n d e s i r a b l e . H o w e v e r , s u c h t e c h n i c a l p r o b l e m s c a n be o v e r c o m e as i n t h e c a s e o f t h e s y n t h e t i c p y r e t h r o i d s w h e r e s p e c i f i c s t e r e o i s o m e r s o f h i g h p u r i t y a r e now p r o d u c e d on a commercial s c a l e . Screening f o r b i o l o g i c a l a c t i v i t y also presents a major


325


326


problem. B i o l o g i c a l t e s t i n g f o r many t y p e s o f a c t i v i t y i s important. I n s c r e e n i n g f o r i n s e c t i c i d a l a c t i v i t y , t h e number o f compounds p a s s i n g t h r o u g h r e s e a r c h a n d d e v e l o p m e n t s t e p s f r o m s y n t h e s i s t o m a r k e t p e r c o m m e r c i a l p r o d u c t was 1 4 , 5 0 0 i n 1 9 7 9 c o m p a r e d w i t h 1,800 i n 1956 ( 9 ) . The number o f compounds t h a t must be s c r e e n e d w i l l r i s e c o n s i d e r a b l y as t h e end o f t h e c e n t u r y approaches. Thus, s c r e e n i n g must be r a p i d o r m o d i f i e d p r o c e d u r e s must be d e v i s e d . The p r o b l e m o f t e s t i n g f o r t y p e s o f b i o l o g i c a l a c t i v i t y other than d i r e c t t o x i c i t y t o t h e t a r g e t o f t e n presents additional complexity. I f t h e t y p e o f a c t i v i t y t o be examined i s n o t d i r e c t l y l e t h a l , i . e . control o f thepest o r suppression o f pest p o p u l a t i o n i s a c h i e v e d through e f f e c t s on b e h a v i o u r , development o r r e p r o d u c t i o n , t h e p r o b l e m o f b i o l o g i c a l t e s t i n g may become much m o r e d i f f i c u l t , a s may a l s o t h e p r o b l e m o f d e m o n s t r a t i n g efficacy. I t i s i nthese areas i n which t h e spectrum o f b i o l o g i c a l a c t i v i t y o f n a t u r a l p r o d u c t s i s most l i k e l y t o be concentrated. The i n t e r f a c e between h o s t and p e s t o r g a n i s m s i s m o d i f i e d by a v a r i e t y o f chemical i n t e r a c t i o n s . To u n d e r s t a n d these complex i n t e r r e l a t i o n s h i p s i s a d i f f i c u l t g o a l , b u t t h e e x p l o i t a t i o n o f " n a t u r a l products** f o r t h e b e n e f i t o f a g r i c u l t u r e w i l l depend on p r o g r e s s towards i t . Economic

Aspects

A major problem i n achieving t h i s goal i st h equestion o f resources. T h e U.S. l o s e s a c o n s i d e r a b l e p e r c e n t a g e o f i t s a g r i c u l t u r a l p r o d u c t i o n t o p e s t s and a l s o pays h e a v i l y t o c o n t r o l pests. Such l o s s e s have been e s t i m a t e d a t about $10 b i l l i o n annually (10). However, t h e b e n e f i t o f r e d u c i n g l o s s e s cannot be measured c o m p l e t e l y i n monetary terms. F a c t o r s such as improved environmental q u a l i t y , c o n s e r v a t i o n and u t i l i z a t i o n o f l a n d and water resources a r ed i f f i c u l t t o include i n the a r i t h m e t i c o f potential benefits. The supremacy o f p e s t i c i d e c h e m i c a l s as c o n t r o l agents has i n f l u e n c e d t h eprocess o f c o n t r o l l i n g pests by emphasizing t h e p r o f i t a b i l i t y o f a market as a major c r i t e r i o n f o r development. Such a c r i t e r i o n i s u s e f u l , b u t l i m i t e d i n i t s applicability. The e l i m i n a t i o n o f t h e screwworm f l y f r o m t h e s o u t h e r n U n i t e d S t a t e s p r o v i d e s an example o f a s u c c e s s f u l a l t e r n a t i v e approach t o c o n t r o l o f a major pest. Benefits to the farmer and consumer a r e a measure o f t h e degree o f success o f t h i s programme. The d e v e l o p m e n t o f i n d i v i d u a l n a t u r a l p r o d u c t s t r u c t u r e s a s p e s t i c i d e s w i l l b e s u b j e c t t o t h e same e c o n o m i c f a c t o r s t h a t affect synthetic pesticides. N a t u r a l p r o d u c t s do n o t d i f f e r f r o m c o m p o u n d s s y n t h e s i z e d i n t h e l a b o r a t o r y , b u t t h e y may, a s p r o d u c t s o f b i o l o g i c a l p r o c e s s e s , be more r e a d i l y d e g r a d e d t h a n many man-made s t r u c t u r e s . A l t h o u g h t h e p o t e n t i a l f o r f a c i l e d e g r a d a t i o n may h a v e f a v o u r a b l e i m p l i c a t i o n s f o r e n v i r o n m e n t a l safety, there i sl i t t l e j u s t i f i c a t i o n f o r t h e assumption a p r i o r i . t h a t b e c a u s e a compound i s a n a t u r a l p r o d u c t , i t p o s s e s s e s no u n d e s i r a b l e t o x i c o l o g i c a l p r o p e r t i e s . Toxicological t e s t s m u s t b e p e r f o r m e d f o r b o t h n a t u r a l a n d man-made c o m p o u n d s b e f o r e r e g i s t r a t i o n as p e s t i c i d e s .


23.

PLIMMER



The c o s t o f d e v e l o p i n g a n d r e g i s t e r i n g a p e s t i c i d e f o r t h e U.S. m a r k e t i s a b o u t $20 m i l l i o n (11). T h e r e f o r e , t h e compounds d e v e l o p e d must have a l a r g e p o t e n t i a l market. F o r an i n s e c t i c i d e , t h i s i m p l i e s b r o a d s p e c t r u m a c t i v i t y and use on s e v e r a l major crops. W o r l d w i d e , o n l y a few m a j o r i n d u s t r i a l c o r p o r a t i o n s possess adequate resources to undertake such activity. T h u s , i t w i l l be d i f f i c u l t t o r e a l i s e t h e p o t e n t i a l o f natural products f o r pest c o n t r o l without recourse to a broader i n s t i t u t i o n a l framework. The b i o l o g i c a l a c t i v i t y a s s o c i a t e d w i t h n a t u r a l p r o d u c t s i s o f t e n s p e c i e s - s p e c i f i c . For example, s u p p r e s s i o n of i n s e c t p o p u l a t i o n by m a s s - t r a p p i n g o r by m a t i n g d i s r u p t i o n r e l i e s on technology t h a t i s s p e c i f i c f o r the t a r g e t i n s e c t . Such s p e c i f i c p e s t c o n t r o l m e t h o d s h a v e t h e m e r i t t h a t t h e y do n o t adversely a f f e c t b e n e f i c i a l i n s e c t s , but they are r a r e l y appealing to the major commercial investor. The s p e c i f i c i t y o f s u c h m e t h o d s a n d t h e i r low p o t e n t i a l f o r e n v i r o n m e n t a l p o l l u t i o n appears t o o f f e r g r e a t p r o m i s e and, t o s t i m u l a t e t h e i r d e v e l o p m e n t , t h e r e has been an a p p r o p r i a t e r e s p o n s e a t t h e p o l i t i c a l l e v e l . Simplified t o x i c i t y and o t h e r t e s t i n g p r o c e d u r e s h a v e b e e n p r o p o s e d by t h e U.S. E n v i r o n m e n t a l P r o t e c t i o n Agency f o r b i o c h e m i c a l s to f a c i l i t a t e r e g i s t r a t i o n (12). A l t h o u g h the r e g u l a t o r y a g e n c i e s have i n d i c a t e d t h e i r i n t e r e s t i n s t i m u l a t i n g new m e t h o d s o f p e s t c o n t r o l as a l t e r n a t i v e s t o the use o f c o n v e n t i o n a l p e s t i c i d e s , t h e p r o b l e m s o f e c o n o m i c and s c i e n t i f i c d e v e l o p m e n t o f s u c h t e c h n i q u e s remain. T h e r e i s o f t e n much d i s p a r i t y i n p r o g r e s s i n d i f f e r e n t f i e l d s of science. B r e a k t h r o u g h s o f t e n a r i s e when new techniques o r i d e a s a r e t r a n s f e r r e d f r o m one f i e l d o f e n d e a v o u r t o a n o t h e r . Such a p r o c e s s o f c r o s s f e r t i l i z a t i o n i s h i n d e r e d by r i g i d academic s e p a r a t i o n of b a s i c d i s c i p l i n e s . The information r e q u i r e d f o r s u c c e s s f u l p e s t c o n t r o l does not r e s i d e s o l e l y i n the hands o f the c h e m i s t , but the c o o p e r a t i o n o f s e v e r a l s p e c i a l i s t s i s e s s e n t i a l . T h i s a p p l i e s p a r t i c u l a r l y t o methods of insect c o n t r o l that involve m o d i f i c a t i o n of behaviour through t h e use o f a t t r a c t a n t s , r e p e l l e n t s o r r e s i s t a n t p l a n t s . Resistant

Plants

and

Ecological

Chemistry

N a t u r a l p r o d u c t c h e m i s t r y has e v o l v e d t h r o u g h t h e s t a g e s o f s t r u c t u r a l e l u c i d a t i o n to the examination of the f u n c t i o n of n a t u r a l compounds w i t h i n e c o l o g i c a l s y s t e m s . Ecological chemistry i s a growing f i e l d of science i n which p l a n t - i n s e c t , p l a n t - p l a n t , and o t h e r i n t e r o r g a n i s m a l r e l a t i o n s h i p s c a n be e x a m i n e d i n t e r m s o f t h e e f f e c t s o f c h e m i c a l s on b i o l o g i c a l f u n c t i o n s , t h u s p r o v i d i n g a more f u n d a m e n t a l a p p r e c i a t i o n o f p l a n t r e s i s t a n c e and t h e i n t e r r e l a t i o n s h i p b e t w e e n p e s t s a n d a g r i c u l t u r a l crops. There i s a chemical b a s i s f o r the interdependence of i n s e c t a n d p l a n t l i f e w i t h i n an e c o s y s t e m . Although the i n f l u e n c e of h e r b i v o r e s , d i s e a s e s , e t c . a n d t h e m o r p h o l o g y o f i n s e c t s and p l a n t s are a l s o important, the n u t r i t i o n a l s t a t u s of the p l a n t h o s t s s i g n i f i c a n t l y a f f e c t s t h e s u r v i v a l o f an i n s e c t c o m m u n i t y


327


328


and i t s v i g o r . Despite s i m i l a r i t i e s i n the major c o n s t i t u e n t s o f p l a n t s , i n s e c t s a r e h i g h l y s e l e c t i v e i n t h e i r f e e d i n g and other b e h a v i o u r s , such as o v i p o s i t i o n , t h a t o c c u r i n a s s o c i a t i o n w i t h a s p e c i f i c host. I n t h i s respect, secondary plant products a r e e x t r e m e l y i m p o r t a n t a n d many t h o u s a n d s o f s e c o n d a r y p l a n t compounds have been e l a b o r a t e d d u r i n g t h e c o u r s e o f p l a n t evolution. Swain (13) d i s c u s s e d t h e o c c u r r e n c e and v a r i a t i o n o f s e c o n d a r y compounds i n t e r m s o f p l a n t a n d i n s e c t c o e v o l u t i o n . Some o f t h e c o n t r o v e r s y c o n c e r n i n g t h e r o l e o f i n s e c t s i n c o e v o l u t i o n has been summarized i n an a r t i c l e by Feeny ( 1 4 ) . I n terms o f a g r i c u l t u r a l p e s t c o n t r o l , he s u g g e s t s t h a t r e s e a r c h s h o u l d c o n c e n t r a t e o n t h e d i v e r s i t y o f compounds i n p l a n t s t h a t are t o x i c a t the metabolic l e v e l ( a n t i b i o s i s ) r a t h e r than a t t h e b e h a v i o u r a l l e v e l (nonpreference r e s i s t a n c e ) . Feeny a l s o discusses t h e concept o f "apparency", which i st h e s u s c e p t i b i l i t y o f p l a n t s o r p l a n t t i s s u e t o be d i s c o v e r e d b y i n s e c t s . A g r i c u l t u r a l p r a c t i c e s often favour t h e "apparency" o f plants when m o n o c u l t u r e s e x t e n d i n g o v e r l a r g e a r e a s p r e s e n t a n a t t r a c t i v e host f o r i n s e c t s . Thus, a d d i t i o n a l defences a r e needed o v e r and above t h o s e r e q u i r e d i n a n a t u r a l community. Defences i n c l u d e crop p r o t e c t i o n chemicals and t h e c u l t i v a t i o n o f p l a n t s w i t h a high degree o f i n s e c t r e s i s t a n c e . The r e d u c t i o n o f "apparency", e.g. by c r o p r o t a t i o n , would reduce t h e need f o r d e f e n s i v e measures and might improve agronomic q u a l i t y by f a v o u r i n g p l a n t s i n which c o n s i d e r a b l e m e t a b o l i c r e s o u r c e s were n o t expended on s y n t h e s i s o f d e f e n s i v e compounds. Resistant crop plants arethe subject o f intensive programmes o f r e s e a r c h . S t u d y o f t h e r e l a t i o n s h i p s among c h e m i c a l c o m p o s i t i o n , v a r i e t y a n d i n s e c t r e s i s t a n c e h a s , i n many i n s t a n c e s , made i t p o s s i b l e t o c o r r e l a t e o b s e r v e d r e s i s t a n c e t o insect attack with plant chemistry. H o w e v e r , r e s i s t a n c e may b e conferred by f a c t o r s other than chemical composition, n o r i s p l a n t r e s i s t a n c e always compatible w i t h agronomic q u a l i t y . This p r o b l e m a n d t h e p r o b l e m o f d i s c o v e r i n g new s o u r c e s o f r e s i s t a n t germplasm are major l i m i t a t i o n s o f t h e technique. Although the h o s t - p l a n t r e s i s t a n c e method o f c o n t r o l u t i l i z e s mechanisms t h a t have e v o l v e d n a t u r a l l y , t h e s e l e c t i o n o f a g r o n o m i c a l l y valuable s p e c i e s f o r c u l t i v a t i o n b y man i n t e r f e r e s s u b s t a n t i a l l y w i t h t h e evolutionary process. The mechanisms o f r e s i s t a n c e have been summarized (15) as n o n p r e f e r e n c e r e s i s t a n c e , a n t i b i o t i c r e s i s t a n c e , and t o l e r a n c e . I n t h e case o f nonpreference r e s i s t a n c e , t h eplant i sl e s s s u i t a b l e f o r food, o v i p o s i t i o n o r s h e l t e r a n d r e s i s t a n c e may i n v o l v e c h e m i c a l o r p h y s i c a l f a c t o r s . The c h e m i c a l b a s i s o f r e s i s t a n c e i s g o v e r n e d b y t h e c o m p l e x o f compounds t h a t a f f e c t i n s e c t b e h a v i o u r , s u c h a s f e e d i n g deterrents, oviposition deterrents, attractants, etc. i n contrast t o a n t i b i o t i c r e s i s t a n c e where t h e presence o r absence o f compounds t h a t a f f e c t t h e d e v e l o p m e n t o r s u r v i v a l o f t h e i n s e c t is involved. Tolerance t o insects i sthea b i l i t y o f theplant t o s u r v i v e a t t a c k b e c a u s e p e s t damage i s r e p a i r a b l e o r d o e s n o t impair thevigour o f theplant. K n i p l i n g (16) d i s c u s s e s t h e e f f e c t o f t h e t y p e s o f r e s i s t a n c e on i n s e c t p o p u l a t i o n and c o n s i d e r s t h a t a n t i b i o t i c r e s i s t a n c e s h o u l d have t h e g r e a t e s t



PLIMMER


329

effect. High m o r t a l i t y should cause a d e c l i n e i n i n s e c t populations. T h i s w i l l , o f c o u r s e , d e p e n d on t h e r a t e o f i n c r e a s e o f i n s e c t p o p u l a t i o n s and t h e l e v e l o f a n t i b i o t i c r e s i s t a n c e , among o t h e r f a c t o r s . E x p e r i m e n t a l e v a l u a t i o n o f e f f e c t s on i n s e c t p o p u l a t i o n s p r e s e n t s a m a j o r s o u r c e o f d i f f i c u l t y and i t was e m p h a s i z e d i n t h e p r e c e d i n g d i s c u s s i o n t h a t a t o t a l e c o s y s t e m s t u d y w o u l d be r e q u i r e d t o determine the e f f e c t i v e n e s s of such c o n t r o l measures and t h a t s m a l l p l o t s a r e i n a d e q u a t e . Resistant plant varieties a r e a d v a n t a g e o u s b e c a u s e t h e y r e d u c e numbers o f i n s e c t s , b u t f r o m the p o i n t of view of the chemist seeking leads to s t r u c t u r e s of h i g h b i o l o g i c a l a c t i v i t y , t h e s t u d y may be d i s a p p o i n t i n g p a r t i c u l a r l y i f a number o f f a c t o r s a r e i n v o l v e d . In studies of r e s i s t a n c e , t e s t s f o r i n s e c t i c i d a l a c t i v i t y p e r s e may y i e l d o n l y limited information. Although pyrethroids, rotenoids, n i c o t i n e , r y a n o d i n e , and a number o f o t h e r p l a n t c o m p o n e n t s a r e i n s e c t i c i d a l , i t i s i m p o r t a n t i n a s c r e e n i n g programme t o r e c o g n i z e c o m p o u n d s t h a t may a f f e c t i n s e c t d e v e l o p m e n t , s u c h as t h e p r e c o c e n e s ( 4 ) , e c d y s o n e s ( 1 7 ) , j u v e n i l e hormone m i m i c s ( 1 7 ) , as w e l l as c o m p o u n d s t h a t a f f e c t i n s e c t b e h a v i o u r , s u c h as t h e t a n n i n s , a z a d i r a c h t i n , and a n u m b e r o f t e r p e n o i d s w h i c h a c t as insect antifeedants. Chemical f a c t o r s are a l s o i n v o l v e d i n the r e s i s t a n c e of p l a n t s t o d i s e a s e and i n t h e c o m p e t i t i v e a b i l i t y o f a p l a n t t o s u r v i v e w i t h i n a community of p l a n t s . P l a n t s t r e s s may also g e n e r a t e a c h e m i c a l r e s p o n s e g i v i n g r i s e t o c o m p o u n d s known as t h e p h y t o a l e x i n s , t h e n a t u r e o f w h i c h w i l l d e p e n d on t h e chemistry of the host p l a n t (18, 19). Such response t o i n j u r y i n f e c t i o n i s o f g r e a t i n t e r e s t b e c a u s e i t has stimulated i n v e s t i g a t i o n s of the nature of the b i o r e g u l a t o r y processes involved.

or

T h i s i s i l l u s t r a t e d i n the case o f g r a p e v i n e s where the e x p l o i t a t i o n of the defences of the p l a n t a g a i n s t f u n g a l a t t a c k b y v i n e downy m i l d e w ( P l a s m o p a r a v i t i c o l a ) and B o t r y t i s c i n e r e a has been s t u d i e d ( 2 0 ) . A group of p h y t o a l e x i n s , the v i n i f e r i n s , w h i c h may be f o r m e d b y o l i g o m e r i z a t i o n o f r e s v e r a t r o l ( a t r i h y d r o x y - t r a n s - s t i l b e n e ) were found o n l y i n i n f e c t e d or i n j u r e d v i n e l e a v e s and had m o d e r a t e a n t i f u n g a l a c t i v i t y i n v i t r o . Pryce (21) a l s o d i s c u s s e d t h e f o r m a t i o n o f a n t i f u n g a l compounds i n r i c e l e a v e s when t h e r i c e was t r e a t e d w i t h 2,2~dichloro-3,3-dimethylcyclopropane carboxylic acid. Responses t h a t a r e e l i c i t e d when t h e n a t u r a l d e f e n c e s o f t h e p l a n t a r e s t i m u l a t e d s u g g e s t new a p p r o a c h e s t o t h e c o n t r o l o f d i s e a s e s o r pests. Natural

P r o d u c t s as

L e a d s t o New

Pesticides

N a t u r a l p r o d u c t s h a v e p r o v i d e d l e a d s t o new p e s t i c i d e s . K n o w l e d g e o f t h e b i o l o g i c a l a c t i v i t y o f many p l a n t s h a s b e e n r e c o r d e d i n t h e a n c i e n t p h a r m a c o p o e i a s o f I n d i a and C h i n a a n d i s p r e s e r v e d i n the f o l k l o r e of most n a t i o n s . The practical a p p l i c a t i o n o f much o f t h i s k n o w l e d g e h a s p r o v e d d i f f i c u l t b e c a u s e i t h a s b e e n a c c u m u l a t e d t h r o u g h o u t t h e a g e s and i t i s



330

BIOREGULATORS FOR

PEST CONTROL

b a s e d on a m i x t u r e o f e x p e r i e n c e , t r a d i t i o n , and m a g i c . Natural p r o d u c t s c o n t i n u e t o be s o l d as d r u g s o r as i n s e c t i c i d e s i n many p a r t s o f t h e w o r l d and t h e m a r k e t p l a c e i s e v i d e n c e o f t h e i r value. N i c o t i n e i s an e x a m p l e o f a n a t u r a l i n s e c t i c i d e t h a t h a s b e e n i n u s e f o r many y e a r s . P y r e t h r i n , a crude mixture of n a t u r a l p y r e t h r o i d s , was u s e d b y C a u c a s i a n t r i b e s as an i n s e c t i c i d e b e f o r e 1800. The e x t r a c t o f p y r e t h r u m f r o m c h r y s a n t h e m u m c i n a e r i a e f o l u m c o n t a i n s p y r e t h r i n s , c i n e r i n s and jasmolins. A l t h o u g h t h i s p r o d u c t was a v a l u a b l e i n s e c t i c i d e when few e f f e c t i v e i n s e c t i c i d e s were a v a i l a b l e , i t s use i n a g r i c u l t u r e has been l i m i t e d by i t s p h o t o c h e m i c a l i n s t a b i l i t y . Replacement o f s u c h n a t u r a l l y o c c u r r i n g i n s e c t i c i d e s by compounds s y n t h e s i z e d f r o m p e t r o c h e m i c a l s was f a v o u r e d b y w a r t i m e c o n d i t i o n s . S y n t h e t i c i n s e c t i c i d e d e v e l o p m e n t and o f f i c i a l a c t i o n t o a p p r o v e t h e i r use have r e c e i v e d a d d i t i o n a l s t i m u l i because s u p p l i e s o f i m p o r t e d i n s e c t i c i d e s have b e e n r e s t r i c t e d f r o m t i m e t o t i m e by p o l i t i c a l or economic f a c t o r s (22). Thus, attempts t o develop p y r e t h r o i d s w e r e c o n t i n u e d a n d many s u c c e s s f u l s y n t h e t i c a n a l o g u e s have been produced s i n c e the e l u c i d a t i o n of t h e i r structure. Some o f t h e e a r l i e s t o f t h e s e w e r e s y n t h e s i z e d as s o o n as t h e n a t u r e o f t h e a c t i v e m a t e r i a l s h a d b e e n e s t a b l i s h e d (23). I n t h e f o r e f r o n t o f r e s e a r c h on s y n t h e t i c p y r e t h r o i d s h a v e been E l l i o t t and h i s c o - w o r k e r s . As a r e s u l t o f t h e i r s u s t a i n e d e f f o r t , t h e p y r e t h r o i d s h a v e now a c h i e v e d i m p o r t a n t p o s i t i o n i n agriculture. The m a j o r s t r u c t u r a l f e a t u r e s n e c e s s a r y f o r t h e i r a c t i v i t y h a v e b e e n e l u c i d a t e d ( 2 4 ) , a n d t h e r e a r e now many r e l a t e d compounds c o m m e r c i a l l y a v a i l a b l e . The new p y r e t h r o i d i n s e c t i c i d e s h a v e r e q u i r e d many y e a r s f o r s u c c e s s f u l development, notwithstanding the s t r u c t u r a l i n f o r m a t i o n a v a i l a b l e i n 1924. The e n v i r o n m e n t a l p e r s i s t e n c e o f t h e new p y r e t h r o i d s i s g e n e r a l l y l o w e r t h a n t h a t o f t h e o r g a n o c h l o r i n e i n s e c t i c i d e s , and t h e s t r u c t u r e i s c a p a b l e o f extensive m o d i f i c a t i o n with r e t e n t i o n of a c t i v i t y . Fortunately, t h e y w e r e i n t r o d u c e d i n t o a g r i c u l t u r a l u s e a t a t i m e when h e a v y r e l i a n c e on o r g a n o c h l o r i n e i n s e c t i c i d e s was no l o n g e r f e a s i b l e and t h e r e was an u r g e n t n e e d f o r new insecticides. T h i s group i s perhaps the most o u t s t a n d i n g example o f n a t u r a l p r o d u c t s t h a t have p r o v i d e d l e a d s f o r m o d i f i c a t i o n . Other groups o f n a t u r a l l y o c c u r r i n g i n s e c t i c i d e s have been i n v e s t i g a t e d , b u t w i t h o u t t h e same s p e c t a c u l a r d e g r e e o f success. Q u a s s i a , r o t e n o n e s , s a b a d i l l a , r y a n i a , mamey, and s e v e r a l o t h e r p l a n t p r o d u c t s h a v e b e e n u s e d as i n s e c t i c i d e s . The c h e m i s t r y o f t h e m a j o r g r o u p s i s k n o w n , b u t many p l a n t p r i n c i p l e s r e m a i n t o be e x p l o r e d ( 2 5 ) . Screening of n a t u r a l products p r e s e n t s a p r o b l e m and r a i s e s t h e i s s u e o f s u i t a b l e b i o a s s a y i n t e r m s o f i n s e c t s p e c i e s , t h e p a r t o f t h e p l a n t t h a t s h o u l d be e x a m i n e d and t h e a p p r o p r i a t e t e s t s f o r a c t i v i t y . The n u m b e r o f d i s c o v e r i e s o f new i n s e c t i c i d e s b a s e d on n a t u r a l p r o d u c t s t r u c t u r e s as p r o t o t y p e s i s l i m i t e d , although i n s e c t i c i d a l a c t i v i t y i s widely d i s t r i b u t e d i n nature. For e x a m p l e , c a r b a m a t e s o c c u r i n n a t u r e and i t h a s l o n g b e e n known t h a t p h y o s t i g m i n e , an a l k a l o i d f r o m t h e c a l a b a r b e a n , i s t o x i c t o


23.

331


PLIMMER


mammals. H o w e v e r , many o t h e r l i n e s o f t h o u g h t m i g h t h a v e l e d t o t h e i n c l u s i o n o f c a r b a m a t e s i n an i n s e c t i c i d e s c r e e n i n g p r o g r a m m e , a s s u m i n g t h a t t h e y w e r e n o t t o be i n c l u d e d o n a r a n d o m basis. The p o w e r f u l a c t i o n o f some n a t u r a l p r o d u c t s on t h e c e n t r a l n e r v o u s s y s t e m may s u g g e s t t h e i r p o t e n t i a l v a l u e i n i n s e c t control. I f t h e i r m a m m a l i a n t o x i c i t y c a n be r e d u c e d b y s t r u c t u r a l m o d i f i c a t i o n t h e y may be u s e f u l i n s e c t i c i d e s . C a r t a p , a r i c e i n s e c t i c i d e , i s a bisthiocarbamate. I t s s t r u c t u r e was b a s e d on t h a t o f t h e n a t u r a l p r o d u c t , n e r e i s t o x i n , a n e u r o t o x i n i s o l a t e d f r o m s h e l l f i s h , a n d i t i s l i k e l y t h a t an i n v i v o m e t a b o l i c c o n v e r s i o n o f c a r t a p t o n e r e i s t o x i n o r r e l a t e d compound is responsible f o r i t s a c t i v i t y (11).

(CH ) 3

2

NH

CH(CH SCONH ) 2

2

2

^ metabolism

cartap

( C H

}

3 2

N H

^

C H

2y

CH^S nereistoxin.

As s c r e e n i n g t e c h n i q u e s become m o r e s o p h i s t i c a t e d , t h e r a n g e o f c o m p o u n d s t h a t a r e p o t e n t i a l l y v a l u a b l e as l e a d s should increase. A s , an e x a m p l e , t h e a n t i j u v e n i l e h o r m o n e a c t i o n o f t h e p r e c o c e n e s has been c i t e d . T h e i r spectrum of a c t i v i t y i s l i m i t e d , but t h e s t u d y o f t h e i r a c t i o n has r e v e a l e d p o t e n t i a l biochemical target sites. N a t u r a l l y o c c u r r i n g i n s e c t i c i d e s are subject to f l u c t u a t i o n s i n p r o d u c t i o n and a v a i l a b i l i t y and, i n d e v e l o p e d c o u n t r i e s , t h e y can r a r e l y compete e f f e c t i v e l y w i t h m a n u f a c t u r e d p r o d u c t s . A l l new s t r u c t u r e s m u s t f a c e t h e same s e a r c h i n g t o x i c o l o g i c a l e x a m i n a t i o n w h e t h e r t h e y a r e n a t u r a l o r s y n t h e t i c i n o r i g i n and t h e i r e c o n o m i c p o t e n t i a l m u s t , t h e r e f o r e , be e q u a l l y as attractive. A l t h o u g h s u c h f a c t o r s may a p p e a r d i s c o u r a g i n g , c h e m i c a l s t h a t p o s s e s s u n u s u a l modes o f a c t i o n s u c h as b e h a v i o u r - m o d i f y i n g c h e m i c a l s h a v e f o u n d an a c c e p t a b l e p l a c e i n p e s t management. Behavioural

Compounds

Many i n t e r a c t i o n s b e t w e e n i n s e c t s a n d i n s e c t s o r b e t w e e n p l a n t s a n d i n s e c t s a r e m e d i a t e d b y c h e m i c a l s a n d i n t h e s e c t i o n on p l a n t r e s i s t a n c e , t h e r o l e o f n o n p r e f e r e n c e r e s i s t a n c e was discussed. T h e r e has b e e n c o n s i d e r a b l e p r o g r e s s i n i s o l a t i n g and i d e n t i f y i n g compounds t h a t a f f e c t i n s e c t b e h a v i o u r . A recent r e v i e w c o n t a i n s m o r e t h a n 800 r e f e r e n c e s t o t h e l i t e r a t u r e a n d l i s t s o v e r 300 c o m p o u n d s as i n s e c t a t t r a c t a n t s , a t t r a c t a n t p h e r o m o n e s and r e l a t e d c o m p o u n d s t o g e t h e r w i t h t h e c o r r e s p o n d i n g insect species (26). O t h e r pheromones ( t r a i l pheromones, h a i r pencil secretions, e t c . ) , feeding deterrents, oviposition d e t e r r e n t s , an o t h e r t y p e s o f b e h a v i o u r a l c o m p o u n d s a r e n o t i n c l u d e d i n t h i s comprehensive r e v i e w , but the volume of i n f o r m a t i o n on b e h a v i o u r a l c o m p o u n d s i s c o n s t a n t l y b e i n g e x p a n d e d as new c o m p o u n d s a r e i d e n t i f i e d . T h e r e a r e many w a y s i n w h i c h b e h a v i o u r a l c o m p o u n d s may be


332



u s e d i n p e s t management s y s t e m s . Potential application of p h e r o m o n e s a n d a t t r a c t a n t s a n d t h e s t a t u s o f r e s e a r c h was r e c e n t l y summarized (10). A n t i f e e d a n t s h a v e a l s o r e c e i v e d much a t t e n t i o n , p a r t i c u l a r l y e x t r a c t s o f t h e neem t r e e ( M e l i a azdirachta). V o l a t i l e a t t r a c t a n t s , a r r e s t a n t s , and s t i m u l a n t s from p l a n t s a l s o appear promising as topes f o r f u t u r e r e s a r c h . In p r a c t i c e , t h e predominant a p p l i c a t i o n o f i n s e c t pheromones and a t t r a c t a n t s i s f o r d e t e c t i o n and s u r v e y o f infestations. Pheromone t r a p s a r e an e x t r e m e l y v a l u a b l e c o m p o n e n t o f many p e s t m a n a g e m e n t s y s t e m s a n d p r o v i d e information on a n a r e a - w i d e b a s i s t h a t p e r m i t s t i m e l y a p p l i c a t i o n o f c o n t r o l measures. For suppression o r c o n t r o l o f i n s e c t populations, a t t r a c t a n t p h e r o m o n e s o r a t t r a c t a n t s may b e u s e d i n s e v e r a l w a y s : (a) i n combination with b a i t s , t o x i c a n t s , s t e r i l a n t s o r pathogens; (b) mass-trapping; o r (c) t o d i s r u p t mating. The a p p l i c a t i o n o f p h e r o m o n e s t o a r e a - w i d e s u p p r e s s i o n o f p o p u l a t i o n b y p e r m e a t i n g t h e a i r w i t h pheromone t o d i s r u p t m a t i n g c o m m u n i c a t i o n h a s b e e n u s e d i n t h e management o f s e v e r a l m a j o r pest insects. T h e r e h a s b e e n c o n s i d e r a b l e r e s e a r c h a n d some c o m m e r c i a l i n t e r e s t i n t h i s approach. There a r e , however, major p r a c t i c a l p r o b l e m s i n t h e way o f s u c c e s s f u l d e v e l o p m e n t . I thas a major a d v a n t a g e t h a t o n l y a f e w grammes o f p h e r o m o n e p e r h e c t a r e i s needed f o r a p p l i c a t i o n . S i n c e , pheromones a r e g e n e r a l l y degraded r a p i d l y , e n v i r o n m e n t a l burden i s minute compared w i t h t h a t t y p i c a l o f many i n s e c t i c i d e s . T h e p r o b l e m o f p h e r o m o n e f o r m u l a t i o n h a s b e e n t h e s u b j e c t o f much r e s e a r c h b e c a u s e t h e y a r e u s u a l l y l a b i l e a n d v o l a t i l e compounds ( 2 7 ) . One o f t h e m a j o r d i f f i c u l t i e s i n t h e u s e o f pheromones ( o r o t h e r n o n l e t h a l methods of c o n t r o l ) i st h ed i f f i c u l t y o f demonstrating e f f i c a c y (28). Extremely large p l o t sizes areusually necessary t o acquire s u f f i c i e n t i n f o r m a t i o n , p a r t i c u l a r l y i f i t becomes n e c e s s a r y t o measure t h e impact o f t h e t r e a t m e n t on m a t i n g and p o p u l a t i o n . R e s e a r c h o n t h e g y p s y moth o v e r a number o f y e a r s h a s demonstrated t h e d i f f i c u l t i e s and d e f i n e d t h e l i m i t s o f t h e technique f o r t h i s species (29). Although thetechnique suffers from the d i s a d v a n t a g e t h a t c o n s i d e r a b l e knowledge o f t h e p o p u l a t i o n dynamics and mating behaviour o f t h e t a r g e t species are e s s e n t i a l p r e r e q u i s i t e s f o r a p p l i c a t i o n , l i m i t e d successes are encouraging continued t r i a l s and development. The u s e o f b e h a v i o u r - m o d i f y i n g c o m p o u n d s o f f e r s g r e a t p r o m i s e f o r i n t e g r a t e d s y s t e m s o f p e s t management, b u t i t r e q u i r e s s u b s t a n t i a l knowledge o f t h e t a r g e t s p e c i e s . M o d i f i c a t i o n o f s t r u c t u r e o f b e h a v i o u r - m o d i f y i n g compounds f o r p o p u l a t i o n s u p p r e s s i o n i s a p o t e n t i a l a p p r o a c h a n d , i n some c a s e s , a n a l o g u e s a r e o f v a l u e i n m a t i n g d i s r u p t i o n . However, t h e r e s p o n s e o f an i n s e c t t o pheromones depends on v e r y p r e c i s e s t r u c t u r a l requirements and even s l i g h t m o d i f i c a t i o n o f s t r u c t u r e normally reduces t h eb i o l o g i c a l a c t i v i t y by s e v e r a l orders o f magnitude. I n v e s t i g a t i o n o f t h e p h y s i o l o g y o f pheromone p r o d u c t i o n h a s


23.

PLIMMER


shown t h a t i n the f e m a l e c o r n earworm moth ( H e l i o t h i s zea) pheromone p r o d u c t i o n i s c o n t r o l l e d by a b r a i n hormone ( 3 0 ) . The s t i m u l a t i o n o f p h e r o m o n e p r o d u c t i o n b y t h i s h o r m o n e i s an important stage i n the r e p o r d u c t i v e process. Such key e v e n t s i n t h e r e p r o d u c t i v e p r o c e s s s u g g e s t new p o t e n t i a l f o r i n s e c t i c i d a l modes o f a c t i o n .


Conclusion N a t u r a l products are a r i c h source of s t r u c t u r a l v a r i e t y . They may p r o v i d e s o u r c e m a t e r i a l s f o r s c r e e n i n g p r o g r a m m e s t o d e t e c t b i o l o g i c a l a c t i v i t y and n a t u r a l p r o d u c t s t h a t p o s s e s s k n o w n a c t i v i t y may s e r v e as t e m p l a t e s f o r s t r u c t u r a l m o d i f i c a t i o n . An o u t s t a n d i n g example of the o p t i m i z a t i o n of s t r u c t u r e t o improve p o t e n c y and s t a b i l i t y i s t h e s y n t h e s i s and s u c c e s s f u l c o m m e r c i a l i z a t i o n o f p y r e t h r o i d s and t h e i r a n a l o g u e s . B a c t e r i a p r e s e n t g r e a t p o t e n t i a l as s o u r c e s o f b i o l o g i c a l l y active chemicals. Developments i n biotechnology should g r e a t l y i n c r e a s e t h e f e a s i b i l i t y o f m a n u f a c t u r i n g new b a c t e r i a l p r o d u c t s in quantity. As a f u t u r e a p p r o a c h t o i n s e c t c o n t r o l , t h e prospect of t r a n s f e r r i n g the c a p a b i l i t y to produce s e l e c t i v e i n s e c t t o x i n s f r o m b a c t e r i a t o p l a n t s may l i e w i t h i n t h e p o t e n t i a l o f new g e n e t i c e n g i n e e r i n g techniques. S u c h d e v e l o p m e n t s i n b i o l o g y as t h e e l u c i d a t i o n o f b i o r e g u l a t o r y p r o c e s s e s and t h e d i s c o v e r y o f new r e c e p t o r s i t e s and r e c e p t o r s h a v e b e e n i n s t r u m e n t a l i n t h e d e v e l o p m e n t o f b i o r a t i o n a l p e s t i c i d e s capable of blocking e s s e n t i a l steps i n metabolic processes t h a t are p e c u l i a r to the organism or o r g a n i s m s t h a t a r e t o be c o n t r o l l e d . N a t u r a l p r o d u c t s are the key t o u n d e r s t a n d i n g e c o l o g i c a l systems. T h e r e has been r a p i d p r o g r e s s i n e l u c i d a t i o n o f t h e c h e m i s t r y o f p r i m a r y a n d s e c o n d a r y p l a n t c o m p o n e n t s and i n t h e growth of knowledge of i n s e c t b i o c h e m i s t r y . For i t s a p p l i c a t i o n to pest c o n t r o l , p a r a l l e l developments i n physiology and b e h a v i o u r a l s t u d i e s are e s s e n t i a l f o r r e v e a l i n g the u n d e r l y i n g c o m p l e x o f c h e m i c a l l y m e d i a t e d i n t e r a c t i o n s among o r g a n i s m s . B i o r a t i o n a l m e t h o d s o f c o n t r o l b a s e d on a l t e r e d i n s e c t - p l a n t r e l a t i o n s h i p s a r e b e i n g e f f e c t i v e l y u s e d , i f we e x t e n d t h i s t e r m to describe a p p l i c a t i o n of host plant resistance. Such c o n t r o l methods have been d e v e l o p e d e m p i r i c a l l y ; but the r a t i o n a l b a s i s f o r f u r t h e r d e v e l o p m e n t w i l l be t h e o u t c o m e o f new genetic studies. S u c c e s s i n d e c i p h e r i n g t h e s t r u c t u r e and f u n c t i o n o f n a t u r a l m o l e c u l e s has d r a m a t i c a l l y c h a n g e d t h e a p p r o a c h t o b i o l o g i c a l problems. The s t r u c t u r e a n d f u n c t i o n s o f b i o l o g i c a l m a c r o m o l e c u l e s , p a r t i c u l a r l y n u c l e i c a c i d s and p r o t e i n s a r e r a p i d l y b e c o m i n g known and t h e a b i l i t y t o e n g i n e e r o r a l t e r t h e i r subunits i n l i v i n g organisms provides p o t e n t i a l technology f o r a l t e r i n g b i o l o g i c a l outputs. Thus, the n u t r i t i v e value of a p l a n t p r o t e i n may be i m p r o v e d by c h a n g i n g t h e s e q u e n c e o f a m i n o acids. The i n s e r t i o n o f g e n e s i n t o p l a n t s a n d t h e i r s u b s e q u e n t expression i s a concept that promises a great future development. However, t h e q u e s t i o n o f r e s i s t a n c e t o p e s t s by



334


p l a n t s i s c o m p l i c a t e d b y t h e c o n t r i b u t i o n o f many f a c t o r s , e a c h a f f e c t e d by d i f f e r e n t genes. The e v o l u t i o n o f h o s t - p l a n t p r e f e r e n c e s and p a r t i c u l a r l y , t h e a d a p t a t i o n o f i n s e c t behaviour, a r e i m p o r t a n t f a c t o r s w h i c h r e q u i r e more s t u d y and D e t h i e r ( 3 1 ) has a r g u e d t h a t t h i s i s i m p o r t a n t a t t h e g e n e t i c l e v e l . The behaviour o f i n s e c t s a t t h e f e e d i n g and r e p r o d u c t i v e stages i s c r i t i c a l l y important i ndetermining thepest status o f a species. A l t h o u g h c h e m i c a l s t h a t modify b e h a v i o u r c u r r e n t l y have a r o l e i n p e s t c o n t r o l , t h e i r a p p l i c a t i o n on an area-wide s c a l e i n a t t e m p t s t o s u p p r e s s i n s e c t p o p u l a t i o n s by u s i n g pheromones t o a l t e r m a t i n g b e h a v i o u r s , may m e e t w i t h l i t t l e s u c c e s s u n l e s s t h e b i o c h e m i c a l and b e h a v i o u r a l aspects o f t h e system are w e l l understood. One o f t h e m o s t i m p o r t a n t r o l e s o f n a t u r a l p r o d u c t s i n p e s t c o n t r o l may b e t h e i r r o l e i n s t i m u l a t i n g t h o u g h t . Pest control may b e c o n c e i v e d a s a n a c t i v i t y d i r e c t e d t o w a r d s c h a n g i n g t h e e x i s t i n g c o n d i t i o n s i n an e c o l o g i c a l system f o r t h e b e n e f i t o f man. A better understanding o f the chemically-mediated i n t e r a c t i o n s among o r g a n i s m s w i t h i n t h e s y s t e m s h o u l d make i t p o s s i b l e t o d e v i s e w a y s i n w h i c h m i n i m a l c h a n g e s y i e l d maximum benefits. However, t h i s cannot be a c h i e v e d by t h e c h e m i s t a l o n e , e v e n t h o u g h new m o l e c u l a r b i o l o g y p r o v i d e s a n e x p l a n a t i o n o f b i o l o g i c a l phenomena i n c h e m i c a l t e r m s . Behaviour, population dynamics and o t h e r f a c t o r s a s s o c i a t e d w i t h whole organisms and communities a r e a l s o e s s e n t i a l components o f t h e c o o p e r a t i v e s t u d y r e q u i r e d t o a c h i e v e c o n t r o l o f p e s t s i n an e c o l o g i c a l l y sound and e f f e c t i v e manner.

Literature Cited 1.

Roller, H.; Dahm, K.H.; Sweeney, C.C.; Trost, B.M. Angew. Chem. Int. Ed. 1967, 6, 179. 2. Meyer, A.S.; Schneiderman, H.A.; Hanzmann, E. Proc. nat. Acad. Sci. U.S.A. 1968, 60, 853. 3. Judy, K.J.; Schooley, D.A.; Dunham, L.L.; Hall, M.S.; Bergot, B.J.; Siddall, J.B. Proc. nat. Acad. Sci. U.S.A. 1973, 70, 1509. 4. Bowers, W.S. In "The Juvenile Hormones"; Gilbert, L.I., Ed.; Plenum, New York, 1976, pp. 394-408. 5. Brooks, G.T.; Pratt, G.E.; Jennings, R.C., Nature 1979, 281, 570. 6. Pratt, G.E.; Jennings, R.C.; Hamnett, A.F.; Brooks, G.T. Nature 1980, 284, 320. 7. Quistad, G.B.; Cerf, D.C.; Schooley, D.A.; Staal, G.B. Nature 1981, 289, 176. 8. Kramer, S.J.; Baker, F.C.; Miller, C.A.; Cerf, D.C.; Schooley, D.A.; Menn, J.J. In "Human Welfare and the Environment", Eds. J. Miyamoto et al, Pergamon, New York, 1983, pp. 177-182. 9. Menn, J.J.; Henrick, C.A. Phil. Trans. Roy. Soc. Lond. 1981, Β 295, 57. 10. Klassen, W.; Ridgway, R.L.; Inscoe, M. In "Insect Suppression with Controlled Release Pheromone Systems", Vol.


23. PLIMMER 11. 12. 13. 14. 15.


16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.


335

I, Kydoneius, A.F., Beroza, Μ., Eds.; CRC Press, Boca Raton, FL, 1982, pp. 13-130. Casida, J.E., In "Advances in Pesticide Science" Part I, H. Geissbühler, Ed.; Pergamon, Oxford, 1979, pp. 45-53. EPA "Approvals for Pyrethrum Substitutes Stepped Up", Chemistry and Engineering News, 1979, Oct. 1. Swain, T. Proc. 15th Ann. Cong. Entomol. 1976, pp. 249-256. Feeny, P. In "Natural Products for Innovative Pest Management", Whitehead, D.L., Bowers, W.S., Eds.; Pergamon, Oxford, 1983, pp. 167-185. Painter, R.H. "Insect Resistance in Crop Plots", Univ. Press of Kansas: Lawrence and London, 1968, 520 pp. Knipling, E.F., The Basic Principles of Insect Population Suppression and Management, U.S. Department of Agriculture, Agriculture Handbook No. 512, 1979. Jacobson, M.; Crosby, D.G., "Naturally Occurring Insecticides", Dekker: New York, 1971. Bowers, W.S.; Nishida, R. Science 1980, 193, 542. Kuc, J.; Caruso, F.L. In "Host Plant Resistance to Pests", Hedin, P.Α., Ed.; Am. Chem. Soc. Symp. Series 1977, 62, pp. 90-114. Cruickshank, I.A.M. In "Natural Products and the Protection of Plants", Marino Bettolo G.B., Ed.; Elsevier: Amsterdam, 1976, pp. 509-561. Pryce, R.J., In "Natural Products for Innovative Pest Management", Whitehead, D.L., Bowers, W.S., Eds.; Pergamon: Oxford, 1983, pp. 73-90. "Pesticide Registration Data: Proposed Data Requirements Part III", U.S. Environmental Protection Agency 1982, 40 CFR 158, 53192-53202, EPA 79. Staudinger, L.; Ruzicka, L. Helv. chim. Acta. 1924, 7, 177,201, 212, 236, 245, 377, 390, 406, 442, 448. Elliott, M.; Janes, N.F. Chem. Soc. Rev. 1978, 7, 473. Crosby, D.G., In "Minor Insecticides of Plant Origin", Jacobson, Μ., Crosby, D.G., Eds.; Dekker: New York, 1971, pp. 177-239. Inscoe, M.N., In "In Insect Suppression with Controlled Release Pheromone Systems", Vol. II, Kydoneius, A.F., Beroza, Μ., Eds.; CRC Press: Boca Raton, FL, 1982, pp. 201-295. Kydoneius, A.F.; Beroza, Μ., Eds.; "Insect Suppression with Controlled Rlease Systems", Vols. I & II; CRC Press: Boca Raton, FL, 1982. Roelofs, W.L., Ed.; "Establishing Efficacy of Sex Attractants and Disruptants for Insect Control"; Entomol. Soc. America: College Park, MD, 1979. Plimmer, J.R.; Leonhardt, B.A.; Webb, R.E. In "Insect Pheromone Technology", Leondardt, B.A., Beroze, M. Eds.; Am. Chem. Soc. Symp. Series, 1982, 190, pp. 231-242. Raina, Α.Κ.; Klun, J.A. Science 1984, 225, 531. Dethier, V.G. Proc. 4th Insect/Host Plant Symp. Ent. exp. and appl. 1978, 24,559.

RECEIVED

November 23, 1984


Role of Natural Product Chemistry - ACS Symposium Series (ACS

Recommend Documents