Discovery of florylpicoxamid, a mimic of a macrocyclic natural product
| Autor: | Chenglin Yao, Kevin G. Meyer, Zachary Buchan, Ben Nugent, Karla Bravo-Altamirano, Brian Loy, Jared Rigoli, David M. Jones, Jeremy Wilmot, Kyle A. DeKorver, John F. Daeuble, Ron Heemstra, Jessica Herrick, Yu Lu, Johnathan E. Delorbe |
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| Rok vydání: | 2021 |
| Předmět: |
Antifungal Agents
Macrocyclic Compounds Pyridines Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Biochemistry chemistry.chemical_compound Broad spectrum Structure-Activity Relationship Ascomycota Drug Discovery Molecular Biology Active ingredient Biological Products Natural product Dose-Response Relationship Drug Molecular Structure Organic Chemistry food and beverages Disease control Crop protection Deconstruction (building) chemistry Target site Molecular Medicine Biochemical engineering New crop |
| Zdroj: | Bioorganicmedicinal chemistry. 50 |
| ISSN: | 1464-3391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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