De novo asymmetric synthesis and biological analysis of the daumone pheromones in Caenorhabditis elegans and in the soybean cyst nematode Heterodera glycines

Authors: GUO, HAIBING - Hubei University; LA CLAIR, JAMES - Xenobe Research Institute; Masler, Edward; O'DOUGHERTY, GEORGE - Northeastern University; XING, YALAN - William Patterson University

Submitted to: Tetrahedron
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/8/2016
Publication Date: 4/5/2016
Citation: Guo, H., La Clair, J., Masler, E.P., O'Dougherty, G., Xing, Y. 2016. De novo asymmetric synthesis and biological analysis of the daumone pheromones in Caenorhabditis elegans and in the soybean cyst nematode Heterodera glycines. Tetrahedron. 72(18):2280-2286.

Interpretive Summary: Plant-parasitic nematodes attack all crops of agricultural importance, causing over $10 billion in losses annually to U.S. farmers. Because several chemical pesticides used to control nematodes have been withdrawn from use, growers face a critical need for the discovery of environmentally and economically sound nematode control agents. One approach to discovering new means of controlling nematodes is to identify ways to disrupt their development and infectivity using naturally derived compounds. Nematodes produce specialized compounds called daumones that control development and protect nematodes from stress. We discovered that a specific daumone artificially induces hatch in soybean cyst nematode eggs, which can persist in the field. Such induction prior to planting is fatal to the nematode and will reduce infectivity and crop loss. This discovery is significant because it demonstrates the novel concept that molecules from nematodes themselves can act as highly specific inhibitors of plant-parasitic nematode development, and present significant potential as natural suppression agents. Consequently, this information will be used by researchers in the agrochemical and agricultural biotechnology industries who are developing safe, selective methods for nematode control.

Technical Abstract: The de novo asymmetric total syntheses of daumone 1, daumone 2 and analogs are described. The key steps of our approach are the diastereoselective palladium catalyzed glycosylation reaction, the Noyori reduction of a acetylfuran and a propargyl ketone, which introduce the absolute stereochemistry of the sugar and aglycon portion of daumone, an Achmatowicz rearrangement, an epoxidation and a ring opening installing the remaining asymmetry of daumone. The synthetic daumones 1 and 2 as well as related analogs were evaluated for dauer activity in C. elegans and effects on hatching of H. glycines.