Synthesis, Antifungal Activity, and Plant Systemic Mobility of Amino Acid Conjugates of a Thiasporine A-Derived Phenylthiazole Scaffold

To develop fungicidal candidates with both high antifungal activity and phloem mobility, a total of 34 2-[2-(trifluoromethoxy)phenyl]thiazole-4-carbonyl amino acid and amino acid ester conjugates were designed and synthesized. Their structures were characterized by 1H NMR, 13C NMR, and HRMS. Their in vitro antifungal activities against five phytopathogenic fungi and their phloem and xylem mobility in castor bean seedlings were subsequently evaluated. The results showed that the amino acid conjugates 9a-9p generally exhibited higher antifungal activity than the corresponding amino acid ester conjugates. Compounds 9m and 9n showed good inhibitory activity against Rhizoctonia solani, Sclerotinia sclerotiorum, Phoma citricarpa, and Phytophthora parasitica. Notably, compounds 9f, 9g, 9l, and 9n showed strong inhibitory activity against P. citricarpa at 200 μmol/L, with inhibition rates of 82.82%, 89.86%, 80.45%, and 91.55%, respectively, all higher than that of thifluzamide (29.30%). Mobility assays revealed configuration-related differences in the conjugate-derived material detected in phloem and xylem exudates, with differential hydrolysis to compound 3 contributing substantially to the observed L/D profiles In addition, some L-amino acid conjugates were hydrolyzed in castor bean seedlings to release the unconjugated carboxylic acid precursor (compound 3). These results indicate that appropriate amino acid conjugation can enhance antifungal activity and modulate systemic mobility in plants, providing a basis for the structural design of systemic fungicides.