Biologically Active Natural Products. Potential Use in Agriculture

485 Pages·1988·8.7 MB·English

by  Horace G. Cutler (Eds.)

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ACS SYMPOSIUM SERIES 380
Biologically Active
Natural Products
Potential Use in Agriculture
Horace G. Cutler, EDITOR
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w0 Agricultural Research Service,
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8 U.S. Department of Agriculture
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10 Developed from a symposium sponsored
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8 | d at the 194th Meeting
98 of the American Chemical Society,
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8, New Orleans, Louisiana,
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ber August 30-September 4, 1987
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American Chemical Society, Washington, DC 1988
Library of Congress Cataloging-in-Publkation Data
Biologically active natural products.
(ACS Symposium Series, ISSN 0097-6156; 380).
The distillation of a six-day American Chemical Society
symposium from 30 August-4 September 1987"—Pref.
1
00 Includes bibliographies and index.
w
0.f 1. Natural products in agriculture—Congresses.
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0 I. Cutler, Horace G., 1932- . II. American Chemical
8- Society. Division of Agrochemicals. III. American
98 Chemical Society. Meeting (194th: 1987: New Orleans,
k-1 La.). IV. Series.
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1/ S587.45.B56 1988 631 88-7859
02 ISBN 0-8412-1556-1
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19 Copyright © 1988
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2 American Chemical Society
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bli the code at the bottom of the first page of the chapter.
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Foreword
The ACS SYMPOSIUM SERIES was founded in 1974 to provide a
medium for publishing symposia quickly in book form. The
format of the Series parallels that of the continuing ADVANCES
IN CHEMISTRY SERIES except that, in order to save time, the
papers are not typeset but are reproduced as they are submitted
by the authors in camera-ready form. Papers are reviewed under
the supervision of the Editors with the assistance of the Series
01 Advisory Board and are selected to maintain the integrity of the
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w symposia; however, verbatim reproductions of previously pub
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8 lished papers are not accepted. Both reviews and reports of
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8-0 research are acceptable, because symposia may embrace both
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Preface
BIOLOGICALLY ACTIVE NATURAL PRODUCTS
have been studied by
investigators from many disciplines. The symposium on which this book
was based brought together plant physiologists, plant pathologists,
marine biologists, entomologists, plant taxonomists, plant ecologists,
medicinal chemists, mycologists, pharmacologists, and others whose
01 scientific curiosity about natural products extends into many areas. They
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pr believe and have presented evidence to show that natural products may
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38 indeed have a place in agriculture. More important, however, is their
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8- assertion that although these diverse structures have high specific
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19 activity, the residual effects in the environment may be minimal.
k-
b I am grateful to my colleagues and friends who gave refreshing
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02 insight to their research, as well as to the chairpersons who diligently
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0. sought speakers and topics for the sessions. The section on products
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oi: from microorganisms was organized by Basil A. Burke of the Plant Cell
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8 | Research Institute, Inc., Dublin, CA. Co-chairs of the section on
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9 products from higher plants were Richard G. Powell, Northern Regional
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8, Research Center, Agricultural Research Service, U.S. Department of
2
er Agriculture, Peoria, IL, and David E. Gianassi, Department of Botany,
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e University of Georgia, Athens, GA. Coordinators of the section on
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No products from insects or affecting insects were Murray S. Blum of the
e: Department of Entomology, University of Georgia, Athens, GA, and
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n D Kevin C. Spencer of the Department of Medicinal Chemistry and
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ati Pharmacognosy, University of Illinois, Chicago, IL. I also acknowledge
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bli the generous support of the Division of Agrochemicals of the American
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P Chemical Society.

HORACE G. CUTLER
Richard B. Russell Research Center
Agricultural Research Service
U.S. Department of Agriculture
Athens, GA 30613
May 13, 1988
xi
Chapter 1
Natural Products and Their
Potential in Agriculture
A Personal Overview
Horace G. Cutler
Richard B. Russell Research Center, Agricultural Research Service,
U.S. Department of Agriculture, Athens, GA 30613
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00 Biologically active natural products are derived
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c from three major sources: the fermentation of
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8 microorganisms, higher plants, and insects. How
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8-0 ever, compounds derived from these sources may
8 act within each or all of these domains. That
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k-1 is, compounds derived from microorganisms and
1/b higher plants may affect insects and vice versa.
2 Often, natural products are obtained in limited
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0.1 quantities and small yields do not lend them
doi: 1 tsherlveee sy teoa resx tthenerseiv eh atse sbteienng . inDcruerainsge dt hsey nptahsets is
8 | of natural product templates and their analogs
98 for evaluation in biological systems. Relative
1
8, to these approaches, assorted natural products
ber 2 afrcoymc lmic icprooloyrkgeatnoislsm sa,n din csolmudei nrge laotliigvoeplye pstiimdepsl,e
m
e molecules are examined. The brassinosteroids and
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o photodynamic herbicides, from higher plants, are
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e: discussed. Finally, compounds that are produced
at by insects, or which affect insects, are
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n reviewed.
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ati
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bli In common with my primal ancestors, whose life began in a
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P garden, my first recollections were not so much of people but

of trees, flowers, the sun, rain, clouds, blue sky, and the
sound of the cuckoo. Especially imprinted on my senses was
the peppery smell of lupin at the early age of two, and there
followed the scent of roses and English lavender: dire warn
ings about foxglove and deadly nightshade were issued as I
wandered about gardens. An introduction to the world of
secondary metabolites had started early in life and subse
quently led to my first scientific job, in the mid 1950*s, at
the Boyce Thompson Institute for Plant Research when it was
located in Yonkers, New York. While at the Institute, I came
under the intellectual guidance of Lawrence J. King, who was
something of a genius, and that led me into the area of plant
growth regulators, especially the natural product of both
This chapter not subject to U.S. copyright
Published 1988 American Chemical Society
2 BIOLOGICALLY ACTIVE NATURAL PRODUCTS
animal and plant origin, indole-3-acetic acid. There
followed another period, at the same location, with A. J.
"Chuck" Vlitos who was investigating flowering in plants,
indole chemistry, and the growth promoting effects of long
chain fatty alcohols in collaboration with Donald G. Crosby
(a topic that was quite revolutionary at the time). This
pioneering atmosphere was further enlivened by I.D.J. "Dai"
Phillips who was an exchange pre-doctoral student from P.F.
Wareing's laboratory in Aberystwyth, Wales. His exuberance
for life, and natural products of growth regulatory ilk, was
contagious. He was hot on the trail of the then structurally
unknown substance from Acer pseudoplatanus (and cotton
bolls), abscisic acid. Contemporaneously, the team of P.W.
Zimmerman and A.A. Hitchcock had synthesized the herbicide
1 2,4-dichlorophenoxyacetic acid at Boyce Thompson and, as they
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0 stated, that synthesis was the result of their examining the
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0.c model of indole-3-acetic acid. The former being a substi
38 tuted phenyl, the latter a phenyl-pyrrole. I also married
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8- one of their technicians and, I suppose, my thoughts con
98 cerning natural products for synthetic templates became
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k- subconsciously fixed as I came to know them better.
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1/ A three year stint in the West Indies (Trinidad) led me
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0 into the world of bush medicine (the use of tropical plants
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0. for medicinals) and took me down that curious path of ethno-
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oi: botany. The range of useful plants was extraordinary. There
d were plants in the genus Verbena that induced increased lac
8 | tation in nursing mothers, grasses that broke fevers, and the
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19 bark of a tree which, when steeped in boiling water, gave
8, rise to a tea that caused erections of some duration in
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er males. The trees yielding this compound were obvious even to
mb the untrained eye because near the local villages the bark
ve was generally stripped from ground level to the height which
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N an adult could reach standing on the seat of a bicycle.
e: There are several yarns surrounding the sexual efficacy of
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D the bark, some apocryphal, but all amusing.
on The third part of the triology, insofar as the science is
ati concerned, involved my training in the biochemistry of nema
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bli todes with Lorin Krusberg, at the University of Maryland. It
Pu happened that one of the nematodes under scrutiny, Ditylen-

chus triformis, could be cultured on the fungus Pyrenochaeta
terrestris. Three flasks of that fungal substrate yielded
more indole-3-acetic acid than I had seen from the extraction
of one-quarter acre of sugarcane, and convinced me that fungi
would be excellent sources of biologically active compounds.
My psychological compass was, once again, fixed on a natural
product course. Hence, my interests and training cut across
several fields and at some point the thought crystallized
that apparently divergent disciplines were inter-related.
There are several temptations that confront the author of
a chapter of this nature. One such is the propensity to
intellectually bludgeon anyone who dares to insinuate that
natural products have no real use in agriculture either as
agrochemicals, or as templates for the further synthesis of
biodegradable agrochemicals, by quoting a series of products
1. CUTLER Natural Products in Agriculture 3
that have been used successfully. Among them would be indole
butyric acid, a homolog of the original compound, indole-3-
acetic acid, that first aroused the curiosity of plant physi
ologists because it was shown to be responsible for the photo-
tropic response of plants. And indole-3-butyric acid has been
used by amateur gardeners and horticulturalists to induce
rooting in plant cuttings.
Another well known natural product is gibberellic acid
(GA) which, again, has high specific activity and limited
3
use in grapes and celery where the responses are quite drama
tic. We tend to forget that thirty-five years ago it was a
common horticultural practice to girdle grapes by cutting in
to the bark of the vines just above ground level in order to
increase yields. This was a delicate procedure and often re
1 sulted in the death of the mature vines. With the advent of
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h0 GA- the art of girdling disappeared and was replaced by
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0. spraying vines at flowering time with 100 ppm GA~ solutions
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3 to increase yields 250%! The natural product ethylene, found
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8- in fungi and higher plants, has been used in both the pure
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9 form and as a derivatized chemical (2-chloroethylphosphonic
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k- acid)to ripen a variety of crops from bananas to cherries, to
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1/ oranges.
2
10 The chemistry of the insecticide pyrethrin, the natural
0. product of the Pyrethrum daisy consisting of two viscous
1
oi: liquid esters C2iH28°3' or C22H28°5' is a l so welJ-
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8 | known and it was precisely these mSlecules that laid the
8 foundation for the synthesis of the highly successful pyre-
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8, 1 throids. Various natural lures (pheromones) have also played
2 a decisive part in controlling insects.
er Some of the most interesting insecticidal and antiparasi
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m tic natural products to enter the field have been the avermec-
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ov tins. Their history is unique because of their complexity,
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ate: tthice sfeaqcut entcheat tot hea rfreirvmee natt attihoen fipnraold upcrtosd ugcot st harnodu gthh eai rs ynthe
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n duality as both agrochemicals and pharmaceuticals. Certainly,
o the average Board of Directors would likely be initially
cati negative to developing such elaborate molecules.
bli Another temptation would be to attempt to convince the
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P reader that in the three areas covered by the symposium —

natural products from microorganisms, secondary metabolites
from higher plants, and natural products from insects or that
affect insects — there are myriad examples of secondary
metabolites that have been isolated that have biological
activity and considerable potential as agrochemicals. How
ever, space does not allow for that discussion and further
elaboration would also detract from the contributions made by
the other authors in this volume. Instead, I have chosen a
different approach, which is to discuss compounds that have
been isolated in each of these three categories, have been
shown to possess unique biological activity, and have then
been synthesized. The reason for this approach is that in
these days the burden of proof for a structure no longer
necessarily requires that a compound be synthesized. The
advent of sophisticated NMR techniques and X-ray crystallo-