Chemical Synthesis Laboratory, SB-ISIC-LSYNC, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
J Nat Prod. 2008 Nov;71(11):1891-6. doi: 10.1021/np800409z. Epub 2008 Oct 30.
Aerucyclamides C and D were isolated from the cyanobacterium Microcystis aeruginosa PCC 7806, and their structures established by NMR spectroscopy and chemical transformation and degradation. Acidic hydrolysis of aerucyclamide C (CF(3)CO(2)H, H(2)O) resulted in microcyclamide 7806A. This chemical evidence combined with spectroscopic and physical data suggest a structure revision for microcyclamide 7806A, which incorporates an O-acylated Thr ammonium residue instead of the originally proposed methyl oxazoline ring. We have prepared microcyclamide 7806B upon basic and acidic treatment of microcyclamide 7806A, which suggests that both these compounds are hydrolysis products of aerucyclamide C and that the aerucyclamides A-D are the actual metabolites produced via ribosomal peptide synthesis in M. aeruginosa PCC 7806. Antiplasmodial evaluation established submicromolar IC(50) values for aerucyclamide B against Plasmodium falciparum; low micromolar values for aerucyclamide C were found against Trypanosoma brucei rhodesiense. The compounds were selective for the parasites over a cell line of L6 rat myoblasts and are thus considered for further study as antimalarial agents.
从铜绿微囊藻 PCC 7806 中分离到 Aerucyclamides C 和 D，并通过 NMR 光谱学和化学转化和降解确定了它们的结构。Aerucyclamide C（CF3CO2H，H2O）的酸性水解得到微囊藻 7806A。这种化学证据与光谱和物理数据相结合，表明微囊藻 7806A 的结构修订，其中包含一个 O-酰化 Thr 铵残基，而不是最初提出的甲基恶唑啉环。我们已经通过微囊藻 7806A 的碱性和酸性处理制备了微囊藻 7806B，这表明这两种化合物都是 Aerucyclamide C 的水解产物，并且 Aerucyclamides A-D 是通过铜绿微囊藻 PCC 7806 中的核糖体肽合成实际产生的代谢物。抗疟原虫评估确定 Aerucyclamide B 对恶性疟原虫的亚毫摩尔 IC50 值；发现 Aerucyclamide C 对罗得西亚锥虫的低微摩尔值。这些化合物对寄生虫具有选择性，而对 L6 大鼠成肌细胞系没有选择性，因此被认为是进一步作为抗疟药物的研究。
