Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues
Hongbo Dong, Li Liao, Bin Long, Yufei Che, Ting Peng, Yujiao He, Ling Mei, Bing Xu
Abstract
In this study, lupinifolin ( 1 ) and its natural analogues, mundulin ( 2 ), minimiorin ( 3 ), khonklonginol H ( 4 ), flemichin D ( 5 ), and eriosemaone A ( 27 ), were obtained by chemical synthesis for the first time. Key steps involved an electrocyclization to build the linear pyran rings and a Claisen/Cope rearrangement to install the 8-prenyl substituents. All compounds were assessed for their in vitro antimicrobial activities against clinically relevant human pathogens, including one Gram-negative bacterial strain ( E. coli ATCC 25922) and four Gram-positive bacterial strains ( S. aureus ATCC 29213, E. faecalis ATCC 29212, MRSA21-5, and VRE ATCC 51299). The result indicated that eriosemaone A ( 27 ) was the most potent one against Gram-positive bacteria, with minimum inhibitory concentrations in the range of 0.25–0.5 μg/mL. Mechanistic studies indicated that 27 has good membrane-targeting ability to bacterial inner membranes and can bind to phosphatidylglycerol and cardiolipin in bacterial membranes, thereby disrupting the bacterial cell membranes and causing bacterial death.