Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues
Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues
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DOI：
10.1021/acs.jnatprod.4c00008
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发表时间：
2024-02-19
影响因子：
5.1
通讯作者：
Xu，Bing
中科院分区：
文献类型：
--
作者：
Dong，Hongbo;Liao，Li;Xu，Bing
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 theirin vitroantimicrobial activities against clinically relevant human pathogens, including one Gram-negative bacterial strain (E. coliATCC 25922) and four Gram-positive bacterial strains (S. aureusATCC 29213,E. faecalisATCC 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 that27has 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.
