Synthesis of pyranopyrans related to diplopyrone and evaluation as antibacterials and herbicides

Authors: ROIREAU, JACK - Villanova University; ROSANO, ROBERT - Villanova University; CHEN, THOMAS - Villanova University; Bajsa-Hirschel, Joanna; Schrader, Kevin; Duke, Stephen; WYKOFF, DENNIS - Villanova University; GIULIANO, ROBERT - Villanova University

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2020
Publication Date: 8/18/2020
Citation: Roireau, J.H., Rosano, R.J., Chen, T., Bajsa Hirschel, J.N., Schrader, K.K., Duke, S.O., Wykoff, D., Giuliano, R.M. 2020. Synthesis of pyranopyrans related to diplopyrone and evaluation as antibacterials and herbicides. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.0c02564.
DOI: https://doi.org/10.1021/acs.jafc.0c02564

Interpretive Summary: Analogs of a natural compound produced by certain plant pathogenic fungi were evaluated for their toxicity toward two types of bacteria that cause disease in pond-raised channel catfish in the southeastern United States. One compound was found to possess significant antibacterial activity against one species of the fish pathogenic bacteria. Herbicidal potential of these analogs was tested on one monocot and two dicot plant species. The same, most active compound identified in the antibacterial assessment demonstrated a good phytotoxic activity.

Technical Abstract: Stereoselective syntheses of new pyranopyrans that are related to the natural phytotoxin diplopyrone have been successfully achieved from carbohydrate starting materials in two approaches that are based on C-glycosides as key intermediates. A C-alkynyl glycosides prepared by Ferrier rearrangement was used as the precursor to a new pyranopyran alkyne that showed potent antibacterial activity against the common bacterial pathogen E. ictaluri that causes enteric septicemia (ESC) in catfish, as well as herbicidal activity. New bioassay data for pyranopyran nitrile 4, the most potent of the analogs synthesized to date, were carried out using greenhouse studies that revealed additional herbicidal activity. Other new analogs synthesized included desmethylpyranopyrans prepared by Isobe C-alkynylation-rearrangment/reduction, and RCM-based pyranopyran construction. The antibiotic and phytotoxic activities of the new pyranopyrans synthesized in this study reveal a structure-activity relationship that involves substituents on the non-lactone ring and provide further evidence of the potential of such compounds as antibiotics and herbicides.