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.
|
Authors | Kevin G Meyer, Karla Bravo-Altamirano, Jessica Herrick, Brian A Loy, Chenglin Yao, Ben Nugent, Zachary Buchan, John F Daeuble, Ron Heemstra, David M Jones, Jeremy Wilmot, Yu Lu, Kyle DeKorver, Johnathan DeLorbe, Jared Rigoli |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 50
Pg. 116455
(11 15 2021)
ISSN: 1464-3391 [Electronic] England |
PMID | 34757295
(Publication Type: Journal Article)
|
Copyright | Copyright © 2021 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antifungal Agents
- Biological Products
- Macrocyclic Compounds
- Pyridines
- florylpicoxamid
|
Topics |
- Antifungal Agents
(chemical synthesis, chemistry, pharmacology)
- Ascomycota
(drug effects)
- Biological Products
(chemical synthesis, chemistry, pharmacology)
- Dose-Response Relationship, Drug
- Drug Discovery
- Macrocyclic Compounds
(chemical synthesis, chemistry, pharmacology)
- Microbial Sensitivity Tests
- Molecular Structure
- Pyridines
(chemical synthesis, chemistry, pharmacology)
- Structure-Activity Relationship
|