Discovery of florylpicoxamid, a mimic of a macrocyclic natural product

Abstract

Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid resulted in an active ingredient with a new target site of action for cereal and banana pathogens. Here we demonstrate the creation of a synthetic variant of fenpicoxamid via identification of the structural elements of UK-2A that are needed for anti-fungal activity. Florylpicoxamid is a non-macrocyclic active ingredient bearing two fewer stereocenters than fenpicoxamid, controls a broad spectrum of fungal diseases at low use rates and has a concise, scalable route which is aligned with green chemistry principles. The development of florylpicoxamid represents the first example of using a stepwise deconstruction of a macrocyclic natural product to design a fully synthetic crop protection active ingredient.

Keywords: Crop protection; Disease control; Florylpicoxamid; Fungicide; Natural product mimic.