Novel α-ketoglutarate lactone synthesis and its effect on gibel carp (Carassius auratus gibelio) under saline-alkaline stress

Saline-alkali stress impairs fish growth and metabolic functions (e.g., ammonia-nitrogen metabolism), necessitating effective mitigators such as α-ketoglutarate (AKG). To address limitations in conventional synthesis and efficacy validation, this study (1) developed a novel two-step AKG synthesis route via Michael addition and nucleophilic substitution/hydrolysis; (2) evaluated AKG's effects on gibel carp ( Carassius auratus gibelio ) growth and ammonia-nitrogen metabolism under saline-alkali stress; (3) compared AKG with AKG lactone (AKGD) as nutritional regulators; and (4) established a scalable high-yield AKGD synthesis for industrial applications. We found that dietary 1.0% AKG alleviated stress-induced weight loss, reduced plasma ammonia and urea nitrogen, and restored Na + /K + -ATPase activity in gills and kidneys during a 4-week trial. Analytical characterization revealed commercial/synthesized AKG comprises compound 1 and AKGD (65:35 ratio). Crucially, AKGD matched AKG's physiological benefits while exhibiting better growth in the short term. A cost-efficient, high-yield AKGD synthesis route was concurrently developed. These findings validate AKG and AKGD as potent stress mitigators in saline-alkali aquaculture, with AKGD emerging as the better anti-stress agent. The study advances both scalable synthesis methodology and sustainable utilization strategies for China's saline-alkali water resources. • We developed a novel two-step synthesis of α-ketoglutarate (AKG) with high efficiency. • 1.0% AKG effectively alleviated the saline-alkali-induced stress of crucian carp. • α-Ketoglutarate lactone (AKGD) shows better growth-promoting effects than AKG. • AKGD holds promise as an alternative stress mitigator for saline-alkaline aquaculture. • Economic and efficient AKGD synthesis can be exploited for industrial-scale production.