Total synthesis and antibacterial evaluation of lupalbigenin and isolupalbigenin

Lupalbigenin (<b>1</b>) is an antibacterial isoflavone isolated from <i>Maclura cochinchinensis</i> (Lour.) Corner (Moraceae). In this study, we achieved the first gram-scale synthesis of lupalbigenin (<b>1</b>) from commercially available genistein (<b>2</b>), 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 (<b>1</b>). Antimicrobial activity assays revealed that lupalbigenin (<b>1</b>) exhibited rapid bactericidal activity, inhibited α-hemolysin and biofilm formation, and disrupted bacterial cell membranes. These findings suggest that lupalbigenin (<b>1</b>) is a promising candidate for the development of novel antibiotics to combat bacterial infections.