Diversity-Oriented Synthesis of Natural-Product-like Libraries Containing a 3-Methylbenzofuran Moiety for the Discovery of New Chemical Elicitors.

Natural products are a major source of biological molecules. The 3-methylfuran scaffold is found in a variety of plant secondary metabolite chemical elicitors that confer host-plant resistance against insect pests. Herein, the diversity-oriented synthesis of a natural-product-like library is reported, in which the 3-methylfuran core is fused in an angular attachment to six common natural product scaffolds-coumarin, chalcone, flavone, flavonol, isoflavone and isoquinolinone. The structural diversity of this library is assessed computationally using cheminformatic analysis. Phenotypic high-throughput screening of β-glucuronidase activity uncovers several hits. Further in vivo screening confirms that these hits can induce resistance in rice to nymphs of the brown planthopper . This work validates the combination of diversity-oriented synthesis and high-throughput screening of β-glucuronidase activity as a strategy for discovering new chemical elicitors.