Design and Enantioselective Synthesis of Chiral Pyranone Fused Indole Derivatives with Antibacterial Activities against pv for Protection of Rice.

A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against pv . Bioassays showed that compounds (34)-, (34)-, and (34)- exhibited promising efficacy against , with EC values of 9.05, 9.71, and 5.84 mg/L, respectively, which were superior to that of the positive controls with commercial antibacterial agents, bismerthiazol (BT, EC = 27.8 mg/L) and thiodiazole copper (TC, EC = 70.1 mg/L). Furthermore, single enantiomer (34)- was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against tests at a concentration of 200 mg/L, which slightly surpassed the positive control with TC (curative and protective activities of 47.2% and 48.8%, respectively). Mechanistic studies through molecular docking analysis revealed preliminary insights into the distinct anti- activity of the two single enantiomers (34)- and (34)-, wherein the (34)-configured stereoisomer could form a more stable interaction with DHPS (dihydropteroate synthase). These findings underscore the significant anti- potential of these chiral pyranone fused indole derivatives, and shall inspire further exploration as promising lead structures for a novel class of bactericides to combat bacterial infections and other plant diseases.