Chapter 6
Diverse but Specific Biological Activities of Four Natural Products from Three Fungi 1
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Horace G. Cutler , Eberhard Ammermann , and James P. Springer 1
Richard B. Russell Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA 30613 Badische Anilin- und Sodafabrik Aktiengesellschaft, Landwirtschaftliche Versuchsstation, D-6703 Limburgerhof, Federal Republic of Germany Merck Therapeutic Institute, Rahway, NJ 07065
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Biologically active natural products isolated from fungi fall into three general categories. Those isolated for medicinal antibiotic activity years ago that have not been tested for agricultural use; those recently isolated as mycotoxins that have not been tested in other biological systems; and novel products. Four examples are given. Cyclopenin and cyclopenol, isolated in 1954; 3,7-dimethyl-8-hydroxy-6-methoxyisochroman, isolated in 1979; and the novel metabolite cinereain, isolated in 1987. The diversity of structure, activity and possible applications of these products to agriculture are discussed. One of the great problems i n dealing with b i o l o g i c a l l y active natural products i s that individuals tend to compartmentalize their thinking when i t comes to working with a specific compound and i t s congeners. There i s a lack of perception that these natural substances may have very diverse a c t i v i t i e s i n s p e c i f i c , but unrelated, biological systems. Those who deal with pharmaceuticals, for example antimicrobials, often f a i l to translate their discoveries to other f i e l d s , such as agrochemicals, with the consequence that much potentially valuable material i s l o s t . For some reason, d i s c i p l i n e s f a i l to communicate with each other and work performed within a d i s c i p l i n e may be done for no apparent cause other than the pursuit of pure knowledge. Another d i f f i c u l t y arises i n that a sense of defeat overcomes those who would venture into the i s o l a t i o n of new natural products from microorganisms; their f i r s t reaction i s to say that the odds for discovering novel structures are very slim and their application for p r a c t i c a l use i s even slimmer. In t h i s chapter three classes of compounds, a l l natural products from microorganisms, w i l l be discussed r e l a t i v e to these general observations and should be viewed as cautionary verses (to avoid myopia) for those 0097-6156/88/0380-0079$06.00/0 © 1988 American Chemical Society
Cutler; Biologically Active Natural Products ACS Symposium Series; American Chemical Society: Washington, DC, 1988.
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BIOLOGICALLY ACTIVE NATURAL PRODUCTS
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who are interested i n agrochemical development and those i n volved i n a singular d i s c i p l i n e who would l i k e to d i v e r s i f y their s c i e n t i f i c p o r t f o l i o . Cyclopenin, cyclopenol, diazepam, and related structures. While searching for b i o l o g i c a l l y active structures, espec i a l l y those that i n h i b i t plant growth, we accessed a fungus, isolated from pecan kernels (Carya i l l i n o e n s i s ) , that had undergone insect damage. The organism, i d e n t i f i e d as an aberrant strain of PeniciIlium cyclopium (NRRL 6233) produced two metabolites, cyclopenin and cyclopenol (1), i n addition to another metabolite, compactin (Figure 1), which showed no growth regulatory properties i n the etiolated wheat (Triticum aestiyum L., cv. Wakeland) coleoptile assay (2). Compactin later underwent independent development by the pharmaceutical industry f o r drug use to reduce blood serum cholesterol (3). However, i t transpired that cyclopenin (Figure 2) s i g n i f i cantly inhibited (P
