The enantioselective synthesis and biological evaluation of chimeric promysalin analogs facilitated by diverted total synthesis
The enantioselective synthesis and biological evaluation of chimeric promysalin analogs facilitated by diverted total synthesis
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DOI：
10.1038/ja.2016.4
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发表时间：
2016-04-01
影响因子：
3.3
通讯作者：
Wuest, William M.
中科院分区：
文献类型：
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作者：
Knouse, Kyle W.;Wuest, William M.
脂肪酸的生物合成和随后的修饰在陆地和海洋生物的初级和次级代谢中起着重要作用。其中一种代谢物，肉豆蔻酸(1)是许多次生代谢物的生物合成前体，其中四种如图1（2-5）所示。这些分子都被证明具有广泛的抗菌和抗毒活性，从抑制生物污垢和生物膜的形成到破坏群体感应网络（vide）。我们的实验室最近完成了第一次全合成promysalin((−)-2)，这证实了它的绝对立体化学和强大的物种特异性抗菌活性（亚微摩尔活性对P. aeruginosa）。1,2 1978年，Moore等人3发现lyngic acid（(−)-3）是海洋蓝藻Lyngbya majuscula脂质提取物的主要成分。Gerwick后来研究了这种次级代谢物的生物学特性，并报道(−)-3对革兰氏阳性菌（金黄色葡萄球菌和枯草芽孢杆菌）具有抗菌活性；然而,
The biosynthesis and subsequent modification of fatty acids plays a major role in the primary and secondary metabolism of both terrestrial and marine organisms. One such metabolite, myristic acid (1) is the biosynthetic precursor of a number of secondary metabolites, four of which are depicted in Figure 1 (2–5). These molecules have each been shown to possess a broad range of antibacteral and antivirulence activity ranging from the inhibition of biofouling and biofilm formation to the disruption of quorum-sensing networks (vide). Our laboratory has recently completed the first total synthesis of promysalin ((−)-2), which confirmed both its absolute stereochemistry and potent species-specific antibacterial activity (submicromolar activity against P. aeruginosa). 1, 2 In 1978 Moore et al. 3 identified lyngbic acid,((−)-3) as a major component of the lipid extracts from the marine cyanobacteria Lyngbya majuscula. Gerwick later studied the biological properties of this secondary metabolite and reported that (−)-3 displays antimicrobial activity toward Grampositive bacteria (Staphylococcus aureus and Bacillus subtilis); however,