Discovery of florylpicoxamid, a mimic of a macrocyclic natural product. (15th November 2021)

• Record Type: Journal Article
• Authors: Meyer, Kevin G.; Bravo-Altamirano, Karla; Herrick, Jessica; Loy, Brian A.; Yao, Chenglin; Nugent, Ben; Buchan, Zachary; Daeuble, John F.; Heemstra, Ron; Jones, David M.; Wilmot, Jeremy; Lu, Yu; DeKorver, Kyle; DeLorbe, Johnathan; Rigoli, Jared
• Is Part Of: Bioorganic & medicinal chemistry. Volume 50(2021)
• Publication Date: 2021-11-15
• Subjects: Crop protection -- Disease control -- Fungicide -- Natural product mimic -- Florylpicoxamid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116455
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.