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

Abstract

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 Xanthomonas oryzae pv oryzae (Xoo). Bioassays showed that compounds (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited promising in vitro efficacy against Xoo, with EC 50 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 50 = 27.8 mg/L) and thiodiazole copper (TC, EC 50 = 70.1 mg/L). Furthermore, single enantiomer (3S,4R)-5l was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against Xoo in vivo 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-Xoo activity of the two single enantiomers (3S,4R)-5l and (3R,4S)-5l, wherein the (3S,4R)-configured stereoisomer could form a more stable interaction with XooDHPS (dihydropteroate synthase). These findings underscore the significant anti-Xoo 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.

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

“…Over the past decade, Chi, Huang, Jin and co-workers multiply reported on the NHC-catalyzed asymmetric reactions for the quick construction of novel chiral indole derivatives (Figure ). − These studies successfully achieved functionalization at the C2-, C3-, and C7-positions of the indole skeleton, with a series of novel chiral spirocyclic oxindoles or other new chiral indole-derived heterocycles afforded as the target compounds in generally moderate to excellent yields and moderate to excellent optical purities. Interestingly, these chiral indole derivatives showed promising activities against various plant bacteria, such as Ralstonia solanacearum ( Rs ), Xanthomonas oryzae pv.…”

“…For the derivatization of both the C2- and C3-positions of the indole structure, Chi, Wu, and colleagues designed and synthesized a range of the chiral dihydropyrano[2,3- b ]indole derivatives 2 . , These compounds, including the (3 S ,4 R )-enantiomers, (3 R ,4 S )-enantiomers, and racemates, were methodically assessed for their in vitro antibacterial efficacy against Xoo at concentrations of 100 and 50 mg/L, respectively. Notably, the structurally complex multicyclic chiral compound (3 S ,4 R )- 2a exhibited potent antibacterial activities against Xoo (EC 50 = 5.84 mg/L), which was superior to the commercially available bactericides thiodiazole-copper (TC, EC 50 = 70.1 mg/L) and bismerthiazol (BT, EC 50 = 27.8 mg/L).…”