Chapter 17
Structure and Function Relationships
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in Polyacetylene Photoactivity Y. Yoke Marchant and Geoffrey K. Cooper ARCO Plant Cell Research Institute, 6560 Trinity Court, Dublin, CA 94568
Polyacetylenes and thiophenes have light-independent and photoactivated toxic effects on a wide range of organisms. These b i o l o g i c a l l y active compounds are of academic and practical interest because of their possible role as plant defense compounds and their potential as commercially useful biocidal agents. Many factors influence the extent of damage caused by these compounds and this paper reviews the relationship between structure and function in polyacetylenes and presents data in support of current views.
P o l y a c e t y l e n e s and t h e i r thiophene d e r i v a t i v e s are b i o l o g i c a l l y a c t i v e secondary m e t a b o l i t e s c h a r a c t e r i s t i c o f t a x o n o m i c a l l y advanced p l a n t f a m i l i e s such as the A s t e r a c e a e , the A p i a c e a e , the A r a l i a c e a e and the Campanulaceae, a s w e l l as c e r t a i n groups o f Basidiomycete f u n g i ( 1 - 5 ) . Only seven compounds were d e s c r i b e d between 1902, when Arnaud f i r s t e s t a b l i s h e d the e x i s t e n c e o f a n a t u r a l l y - o c c u r r i n g t r i p l e bond (6), and 1950, when a n t i b i o t i c substances produced by f u n g a l s p e c i e s were i d e n t i f i e d a s a c e t y l e n e s (7-12; F i g u r e 1). S i n c e then s e v e r a l hundred p o l y a c e t y l e n e s have been recorded ( 3 ) , many w i t h t o x i c a c t i v i t y a g a i n s t b i o l o g i c a l systems, because i n v e s t i g a t i o n s i n t o the a n t i b i o t i c p r o p e r t i e s o f p l a n t s and f u n g i o f t e n l e d t o the d i s c o v e r y o f p o l y a c e t y l e n e s a s the active principles. I d e n t i f i c a t i o n was f a c i l i t a t e d by the c h a r a c t e r i s t i c UV s p e c t r a o f conjugated a c e t y l e n e s and by the h i g h e x t i n c t i o n c o e f f i c i e n t s o f the s p e c t r a which p e r m i t t e d d e t e c t i o n o f low q u a n t i t i e s o f compounds i n e x t r a c t s (1,13,14). In 1973 the n e m a t o c i d a l p r o p e r t i e s o f a l p h a - t e r t h i e n y l ( I I ) and 5 - ( 3 - b u t e n - 1 - y n y l ) - 2 , 2 ' - b i t h i e n y l ( I I I ; F i g u r e 2) were found t o be s i g n i f i c a n t l y enhanced by UV l i g h t ( 1 5 ) . T h i s l e d to a s y s t e m a t i c i n v e s t i g a t i o n o f the p h o t o t o x i c p r o p e r t i e s o f p o l y a c e t y l e n e s from the Asteraceae by Towers and h i s a s s o c i a t e s ( 5 , 16-19). The in. v i t r o p h o t o a c t i v i t y o f a c e t y l e n i c compounds a g a i n s t b i o l o g i c a l systems i s now a w e l l e s t a b l i s h e d phenomenon. N e v e r t h e l e s s , many b i o l o g i c a l l y a c t i v e a c e t y l e n e s are not l i g h t - a c t i v a t e d and must be c o n s i d e r e d i n any attempt to understand the s t r u c t u r a l b a s i s f o r the p h o t o t o x i c i t y o f these compounds. T h i s paper w i l l examine the 0097-6156/87/0339-0241 $06.00/0 © 1987 American Chemical Society
Heitz and Downum; Light-Activated Pesticides ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
242
LIGHT-ACTIVATED PESTICIDES
r e l a t i o n s h i p between s t r u c t u r e and b i o l o g i c a l a c t i v i t y i n polyacetylenes.
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Polyacetylenes with Light-Independent B i o l o g i c a l E f f e c t s Bohlmann e t a l . (1) surveyed 32 s p e c i e s i n the Campanulaceae and found t h a t the most commonly o c c u r r i n g a c e t y l e n e s i n t h i s f a m i l y a r e the CiH-ene-diyne-ene t e t r a h y d r o p y r a n y l e t h e r s ( I V ; F i g u r e 3 ) , none o f which appear to be p h o t o s e n s i t i z e r s , or even to have a n t i b i o t i c a c t i v i t y ( 5 ) . The c h a r a c t e r i s t i c compounds o f the Apiaceae and the A r a l i a c e a e , f a l c a r i n o n e and f a l c a r i n d i o l (V, V I ; Table I ) , a r e T a b l e I. B i o l o g i c a l l y a c t i v e C17 a c e t y l e n e s from the Apiaceae and A r a l i a c e a e
0
CH =CH-C-(C=C) -CH -CH=CH-(CH ) -CH 2
2
2
2 6
3
OH CH=CH - C - (C=C) -CH -CH-CH -(CH ) -CH OH 2
2
2
2 6
3
OH CH -(CH ) -CH-(CH ) -(CH=CH) -(C=C) -CH=CH-(CH ) 0H 3
2 2
2 2
2
2
2
2
CH-(CH)-CH-(CH=CH)-(C=C)-CHCHCHOH OH YID 3
2 2
3
2
2
2
2
F a l c a r i n o n e ( V ) , f a l c a r i n d i o l ( V I ) , Daucus c a r o t a L.; o e n a n t h o t o x i n ( V I I ) , Oenanthe c r o c a t a L.; c i c u t o t o x i n ( V I I I ) , C i c u t a v i r o s a L.
a c t i v e a g a i n s t pathogenic and d e r m a t o p h y t i c f u n g i (20-27), i n s e c t s such as Daphnia magna S t r a u b ( 2 8 ) , cause e r y t h r o c y t e h e m o l y s i s (21,29), and have v a r i o u s p h a r m a c o l o g i c a l e f f e c t s ( 3 0 ) , a l l o f which are l i g h t independent. E f f e c t i v e c o n c e n t r a t i o n s d i f f e r f o r each e x p e r i m e n t a l system, but appear to be w i t h i n the range o f 10-5 t o 10-4 M. Two o t h e r C17 p o l y a c e t y l e n e s , o e n a n t h o t o x i n ( V I I ) and c i c u t o t o x i n ( V I I I ) from Oenanthe c r o c a t a L. and C i c u t a v i r o s a L., are much more potent compounds, w i t h w e l l documented f a t a l n e u r o t o x i c e f f e c t s on l i v e s t o c k and humans ( 3 1 ) . A c e t y l e n e s from the Asteraceae a l s o have numerous nonp h o t o a c t i v a t e d b i o l o g i c a l e f f e c t s (Table I I ) . For example, the
Heitz and Downum; Light-Activated Pesticides ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
17.
M A R C H A N T A N DCOOPER
Polyacetylene Photoactivity
H(C=C) -CH=C=CH-(CH=CH) -CH COOH
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2
2
2
F i g u r e 1. The f i r s t f u n g a l a n t i b i o t i c a c e t y l e n e i s o l a t e d from B a s i d i o m y c e t e s . Mycomycin ( I ) , N o c a r d i a a c i d o p h i l u s .
^MgVc^C-CH^H,
F i g u r e 2. P h o t o a c t i v a t e d n e m a t i c i d a l t h i o p h e n e s from t h e Asteraceae. A l p h a - t e r t h i e n y l ( I I ) ; 5-(3-buten-1-ynyl)-2,2' b i t h i e n y l ( I I I ) , T a g e t e s p a t u l a L.
H0CH — CH=CH — (C = C v*/ ) -CH = C H - 0 2 2
2
17
F i g u r e 3. T y p i c a l p o l y a c e t y l e n e from t h e Campanulaceae. Cm-tetrahydropyranylether ( I V ) , Campanula s p p .
Heitz and Downum; Light-Activated Pesticides ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
243
244
LIGHT-ACTIVATED PESTICIDES Table I I . Non-photoactivated polyacetylenes from the Asteraceae
CH -(C=C) , /-CH 3 - v=^ C H - k ^ 3
3
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R«H K R * CH3CO X 0
