Sanofi-Fraunhofer Natural Product Center of Excellence, Fraunhofer IME , Industriepark Höchst Bldg. G878, 65926 Frankfurt am Main, Germany.
Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano SA, Italy.
J Org Chem. 2017 Jun 16;82(12):6032-6043. doi: 10.1021/acs.joc.7b00228. Epub 2017 Jun 6.
Seven new halogenated peptides termed svetamycins A-G (1-7) have been isolated from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are cyclic depsipeptides, whereas svetamycin E is a linear analogue of svetamycin C. Their structures were determined using extensive spectroscopic analysis, and their stereochemical configuration was established by a combination of NMR data, quantum mechanical calculations, and chemical derivatizations. Svetamycins are characterized by the presence of a hydroxyl acetic acid and five amino acids including a rare 4,5-dihydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, a γ-halogenated piperazic acid, and a novel δ-methylated piperazic acid in svetamycins B-C, E, and G. Moreover, isotope-labeled substrate feeding experiments demonstrated ornithine as the precursor of piperazic acid and that methylation at the δ position of the piperazyl scaffold is S-adenosyl-l-methionine (SAM)-dependent. Svetamycin G, the most potent antimicrobial of this suite of compounds, inhibited the growth of Mycobacterium smegmatis with an MIC value of 2 μg/mL.
从一株链霉菌的实验室培养物中分离得到了 7 种新的卤化肽，命名为 Svetamycins A-G（1-7）。Svetamycins A-D、F 和 G 是环状的 depsipeptides，而 Svetamycin E 是 Svetamycin C 的线性类似物。通过广泛的光谱分析确定了它们的结构，并通过 NMR 数据、量子力学计算和化学衍生化的组合确定了它们的立体化学构型。Svetamycins 的特征在于存在羟基乙酸和 5 种氨基酸，包括一种罕见的 4,5-二羟基-2,3,4,5-四氢哒嗪-3-羧酸、γ-卤化哌嗪酸和一种新型的 δ-甲基化哌嗪酸，在 Svetamycins B-C、E 和 G 中。此外，同位素标记的底物喂养实验表明鸟氨酸是哌嗪酸的前体，哌嗪骨架的 δ 位甲基化是 S-腺苷-L-甲硫氨酸（SAM）依赖性的。Svetamycin G 是这组化合物中抗菌活性最强的化合物，对耻垢分枝杆菌的 MIC 值为 2 μg/mL。
