Research advances in L-azetidine-2-carboxylic acid

L-Azetidine-2-carboxylic acid is a non-proteinogenic amino acid present in certain plant species. Characterized by unique azetidine structure (nitrogen-containing four-membered ring), this compound exhibits remarkable chemical reactivity and diverse physiological activities. Currently, the synthesis of L-azetidine-2-carboxylic acid is mainly confined to chemical approaches, with diverse synthetic strategies having being reported. Notably, newly developed synthetic routes have achieved kilogram-scale production, indicating significant industrial production potential. Due to its a strained chiral azetidine ring system, L-azetidine-2-carboxylic acid serves not only as a crucial building block for synthesizing chiral azetidine-containing natural products and bioactive pharmaceutical molecules, but also it has applications in chiral catalysis and pharmacophore design. Biological activity studies reveal that L-azetidine-2-carboxylic acid can competitively mimic proline during protein synthesis, thereby disrupting normal protein metabolism. It exhibits broad inhibitory effects across diverse organisms, including plants, bacteria, viruses, fungi, and cyanobacteria, and also inhibits growth in multiple animal models. Notably, it demonstrates remarkable efficacy against cucurbit powdery mildew and potent inhibition of cyanobacteria, positioning it as a promising candidate for developing novel plant-derived fungicide. Furthermore, the rigid cyclic framework of L-azetidine-2-carboxylic acid, serving as an advantageous structural unit, has been extensively utilized in the structural modification and functional optimization of enzyme inhibitors, antimalarial drugs, and analgesics. This review summarizes the chemical synthesis and fungicidal activity of L-azetidine-2-carboxylic acid, providing a scientific basis for its development as a novel green pesticide.