Discovery, Characterization, and Analogue Synthesis of Bohemamine Dimers Generated by Non-enzymatic Biosynthesis.
Discovery, Characterization, and Analogue Synthesis of Bohemamine Dimers Generated by Non-enzymatic Biosynthesis.
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DOI：
10.1002/chem.201600024
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
MacMillan JB
中科院分区：
文献类型：
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作者：
Fu P;Legako A;La S;MacMillan JB
从一株产于海洋的刺核褐黄链霉菌中分离得到三个新的二聚体波希米亚明类似物Dibohemamines A-C（5-7）。通过光谱分析确定的结构，通过半合成的衍生化的单体bohemamines和甲醛确认。这些反应可能在温和条件下发生，并检测到培养物中的甲醛，表明这种二聚化是一种非酶促过程。除了二波希米亚明的独特二聚化之外，发现二波希米亚明B和C对非小细胞肺癌细胞系A549具有nM细胞毒性。考虑到化合物6和7的强细胞毒性，通过利用一系列芳基和烷基醛产生用于生物评价的波希米亚胺类似物的小文库。
Dibohemamines A–C (5–7), three novel dimeric bohemamine analogs dimerized through a methylene group, were isolated from a marine-derived Streptomyces spinoverrucosus. The structures determined by spectroscopic analysis were confirmed through the semi-synthetic derivatization of monomeric bohemamines and formaldehyde. These reactions, which could occur under mild conditions, together with the detection of formaldehyde in the culture, revealed that this dimerization is a non-enzymatic process. In addition to the unique dimerization of the dibohemamines, dibohemamines B and C were found to have nM cytotoxicity against the non-small cell lung cancer cell line A549. In view of the potent cytotoxicity of compounds 6 and 7, a small library of bohemamine analogs w as generated for biological evaluation by utilizing a series of aryl and alkyl aldehydes.