Total synthesis and antibacterial evaluation of lupalbigenin and isolupalbigenin

Lupalbigenin (1) is an antibacterial isoflavone isolated from Maclura cochinchinensis (Lour.) Corner (Moraceae). In this study, we achieved the first gram-scale synthesis of lupalbigenin (1) from commercially available genistein (2), with a yield of 47.7%. The key step was a Claisen rearrangement that simultaneously installed two prenyl groups at the C-6 and C-11 positions of lupalbigenin (1). Antimicrobial activity assays revealed that lupalbigenin (1) exhibited rapid bactericidal activity, inhibited α-hemolysin and biofilm formation, and disrupted bacterial cell membranes. These findings suggest that lupalbigenin (1) is a promising candidate for the development of novel antibiotics to combat bacterial infections.