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.
View Article and Find Full Text PDFBackground: Following the introduction of fenpicoxamid, a natural product-based fungicide targeting the Qi site of mitochondrial cytochrome bc1 complex, a second generation fully synthetic picolinamide, florylpicoxamid, was discovered and its biological activity and attributes were characterized.
Results: In vitro fungal growth inhibition assays and in planta glasshouse biological activity evaluations showed florylpicoxamid was active against 21 different plant pathogenic fungi within the phyla Ascomycota and Basidiomycota. Among the pathogens evaluated, florylpicoxamid was most potent against Zymoseptoria tritici, the causal organism of wheat leaf blotch, providing 80% growth inhibition in vitro at 0.
Background: Fenpicoxamid (Inatreq™ active), a new fungicide under development by Corteva Agriscience™, Agriculture Division of DowDuPont, is an isobutyryl acetal derivative of the antifungal antibiotic UK-2A. SAR studies around the picolinamide ring and benzyl substituents attached at positions 3 and 8, respectively, of the UK-2A bislactone macrocycle have recently been documented. This study focuses on replacement of the isobutyryl ester group in the 7 position.
View Article and Find Full Text PDFWith the anticipated population growth in the coming decades, the changing regulatory environment, and the continued emergence of resistance to commercial pesticides, there is a constant need to discover new lead chemistries with novel modes of action. We have established a portfolio of approaches to accelerate lead generation. One of these approaches capitalizes on the rich bioactivity of natural products (NPs), highlighted by the numerous examples of NP-based crop protection compounds.
View Article and Find Full Text PDFBackground: UK-2A is an antifungal antibiotic produced by Streptomyces sp. 517-02. Derivatization of its picolinamide OH to form the isobutyryl acetal led to the discovery of fenpicoxamid (InatreqTM active), which is currently under development as a fungicide by Dow AgroSciences LLC.
View Article and Find Full Text PDFBackground: The antifungal antibiotic UK-2A strongly inhibits mitochondrial electron transport at the Q site of the cytochrome bc1 complex. Previous reports have described semi-synthetic modifications of UK-2A to explore the structure-activity relationship (SAR), but efforts to replace the picolinic acid moiety have been limited.
Results: Nineteen UK-2A analogs were prepared and evaluated for Q site (cytochrome c reductase) inhibition and antifungal activity.
Background: The development of novel highly efficacious fungicides that lack cross-resistance is extremely desirable. Fenpicoxamid (Inatreq™ active) possesses these characteristics and is a member of a novel picolinamide class of fungicides derived from the antifungal natural product UK-2A.
Results: Fenpicoxamid strongly inhibited in vitro growth of several ascomycete fungi, including Zymoseptoria tritici (EC , 0.
The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 to enal C9-C22 is reported. The 1,9,18-tris-O-TBDPS ether was converted into the desired 9,18-dihydroxy acid. Its macrolactonization was accomplished by the Shiina method.
View Article and Find Full Text PDFBackground: As a result of resistance development in many plant-pathogenic fungi to agricultural fungicides, there is an ongoing need to discover novel antifungal chemistries to help sustain efficient crop production. A fungicide screening program identified 3-phenyl-1-(2,2,2-trifluoroethyl)-1,2,4-triazin-6(1H)-one (5) as a promising new starting point for further activity optimization. A series of analogs were designed, prepared and evaluated in growth inhibition assays using four plant-pathogenic fungi.
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