Design and synthesis of florylpicoxamid, a fungicide derived from renewable raw materials

Abstract

The design and synthesis of the broad-spectrum fungicide, florylpicoxamid, embodies multiple Green Chemistry principles. The active ingredient was strategically designed to deliver maximum biological activity and rapidly degrade after application to minimize its enviromental impact. Unlike many chiral crop protection chemicals, florylpicoxamid was purposely developed as a single stereoisomer to minimize the dose rate of this product in field applications and avoid any potential environmental burdens of its less active stereoisomers. Fortunately, the most efficacious stereoisomer of the natural product-inspired active ingredient can be derived from the natural antipodes of lactic acid and alanine. The principles of Green Chemistry were also used to improve the synthetic route originally developed for structure–activity relationship studies, resulting in a convergent stereoselective synthesis that is more sustainable and cost-effective. The streamlined 2^nd generation route decreases the use of protecting groups and utilizes safer reaction solvents. Development of a novel synthetic sequence to the 2,3,4-trisubstituted pyridine motif from furfural further increased the renewable carbon content of the active ingredient to nearly 50%. Throughout process development, improved reaction conditions and industrially-preferred alternatives were identified to replace hazardous reagents for key transformations. In all, the holistic use of Green Chemistry principles in the design and synthesis of florylpicoxamid will provide farmers with a highly sustainable product for crop disease management.