New insect pest control agents are needed to meet the demands to feed an expanding global population, to address the desire for more environmentally-friendly insecticide tools, and to fill the loss of control options in some crop-pest complexes due to development of insecticide resistance. The spinosyns are a highly effective class of naturally occurring, fermentation derived insecticides, possessing a very favorable environmental profile. Chemically, the spinosyns are composed of a large complex macrolide tetracycle coupled to two sugars. As a means to further exploit this novel class of natural product-based insecticides, molecular modeling studies coupled with bioactivity-directed chemical modifications were used to define a less complex, synthetically accessible replacement for the spinosyn tetracycle. These studies lead to the discovery of highly insecticidal analogs, possessing a simple tri-aryl ring system as a replacement for the complex macrolide tetracycle.

Simplifying complex natural products: Computer modeling-based design leads to highly insecticidal, chemically simpler synthetic mimics of the spinosyn natural products that are active in the field. SUMMARYOur studies show that the large, complex macrolide tetracycle of the spinosyns can be effectively emulated by a simple tri-aryl Pest Manag Sci 2019; 75: 309-313

The front cover image is based on the Spotlight Discovery of highly insecticidal synthetic spinosyn mimics ‐ CAMD enabled de novo design simplifying a complex natural product by Thomas C Sparks et al., DOI: http://doi.org/10.1002/ps.5217.