Insect Control: Biological and Synthetic Agents - Index of

6 The Spinosyns: Chemistry, Biochemistry,
Mode of Action, and Resistance
V L Salgado, Bayer CropScience AG, Monheim,
Germany
T C Sparks, Dow AgroSciences, Indianapolis,
IN, USA
ß 2010, 2005 Elsevier B.V. All Rights Reserved
6.1. Introduction 207
6.2. Discovery, Structure, and Biosynthesis of the Spinosyns 207
6.2.1. The Spinosyns 208
6.2.2. The 21-Butenyl Spinosyns 211
6.2.3. Spinosyn Biosynthesis 212
6.2.4. Physical Properties of the Spinosyns 213
6.3. Pharmacokinetics of Spinosad 213
6.3.1. Metabolism of the Spinosyns 213
6.3.2. Spinosyn Penetration into Insects 215
6.3.3. Insecticidal Concentration in the Cockroach 215
6.4. Mode of Action of Spinosyns 217
6.4.1. Poisoning Symptoms 219
6.4.2. Gross Electrophysiology 221
6.4.3. Nicotinic Receptors as the Spinosyn Target Site 223
6.4.4. Effects of Spinosyns on GABA Receptors in Small Diameter Neurons of Cockroach 227
6.5. Biological Properties of the Spinosyns 228
6.5.1. Biological Activity and Spectrum of the Spinosyns 228
6.6. Resistance Mechanisms and Resistance Management 232
6.6.1. Cross-Resistance 232
6.6.2. Resistance Mechanisms 232
6.6.3. Resistance Management 233
6.7. Spinosyns and Spinosoid Structure–Activity Relationships 235
6.7.1. Modifications of the Tetracycle 236
6.7.2. Modification or Replacement of the Forosamine Sugar 236
6.7.3. Modification or Replacement of the Tri-O-Methyl-Rhamnose Sugar 237
6.7.4. Quantitative Structure–Activity Relationships and the Spinosyns 238
6.8. Conclusion 239
6.1. Introduction
The spinosyns and associated spinosoids (semisynthetic
analogs of the spinosyns) constitute a new and
unique class of insect control agents. The spinosyns
are fermentation-derived natural products that are
chemically unique (Figure 1). In addition to their
unique chemical structure, the spinosyns possess a
novel mode of action coupled with an insecticidal
efficacy on par with many pyrethroid insecticides,
plus a very favorable toxicological profile (Bret
et al., 1997; Sparks et al., 1999). Thus, the spinosyns
exhibit many highly desirable attributes for an insect
control agent.
The first commercial product, spinosad, was
launched in 1997. An extensive discovery effort followed
the initial isolation and identification of the
first spinosyns. This effort led to the identification of
an array of naturally produced spinosyns, as well as
a variety of semi-synthetic analogs; the spinosoids.
In this chapter attempts are made to bring together
aspects of the discovery of the spinosyns and
spinosoids, their chemistry, biology, mode of action,
structure–activity relationships, and resistance management.
The reader is also referred to several
reviews (Crouse et al., 1999; Sparks et al., 1999;
Anzeveno and Green, 2002; Kirst et al., 2002b).
6.2. Discovery, Structure, and
Biosynthesis of the Spinosyns
Among insecticidal insect control agents, natural
products have in numerous instances become products
or have been the model or inspiration for
insecticidal products. At the very least, virtually all
significant classes of insect control agents, including