The natural products, anaephenes A (1) and B (2), were found to have antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this report, we expanded on our previous synthetic efforts by preparing a library of eighteen analogues in order to understand the structure–activity relationships (SAR) of this interesting class of natural products. These analogues were selected to explore the biological impact of structural variations in the alkyl chain and on the phenol moiety. Last, we further assessed the biological activity of anaephene B (2) and two additional analogues against other clinically relevant bacterial strains and the hemolytic activity of each and determined that these compounds act via a bactericidal mechanism. These studies led to the identification of compound 7, which was 4-fold more potent than the natural product (2) against MRSA (2 vs. 8 μg/ml) and a 2-hydroxypyridine analogue (18) which demonstrated equal potency compared with the natural product (2), albeit with a significant reduction in hemolytic activity (<1% vs. 80% at 100 μM).

中文翻译：

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anaphene 抗生素的设计、合成和构效关系研究

发现天然产物 anaephenes A ( 1 ) 和 B ( 2 ) 对耐甲氧西林金黄色葡萄球菌(MRSA)具有抗菌活性。在本报告中，我们通过准备一个包含 18 个类似物的库来扩展我们之前的合成工作，以了解这类有趣的天然产物的构效关系 (SAR)。选择这些类似物来探索烷基链和苯酚部分结构变化的生物学影响。最后，我们进一步评估了 anaephene B ( 2) 和另外两种针对其他临床相关细菌菌株的类似物以及每种菌株的溶血活性，并确定这些化合物通过杀菌机制起作用。这些研究导致鉴定出化合物7，其抗 MRSA 的效力是天然产物 ( 2 ) 的4 倍(2 vs. 8 μg/ml) 和 2-羟基吡啶类似物 ( 18 )，与 MRSA相比，其效力相同。天然产物 ( 2 )，尽管溶血活性显着降低（<1% vs. 100 μM 时的 80%）。