A latent oxazoline electrophile for N-O-C bond formation in pseudomonine biosynthesis
A latent oxazoline electrophile for N-O-C bond formation in pseudomonine biosynthesis
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DOI：
10.1021/ja804499r
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发表时间：
2008-09-17
影响因子：
15
通讯作者：
Walsh, Christopher T.
中科院分区：
文献类型：
--
作者：
Sattely, Elizabeth S.;Walsh, Christopher T.
氮-杂原子键在天然产物的结构、化学和功能多样性中占有重要地位。在嗜铁假单胞菌假单胞菌的情况下，发现N-O异羟肟酸酯键不常见地配置在异恶唑烷酮环中。在努力了解这个杂环的生物起源，我们已经在体外的假单胞菌合成酶的特点和重建完整的生物合成途径。我们的研究结果表明，异恶唑烷酮的假单胞菌来自自发重排的恶唑啉前体。据我们所知，这是一种以前未表征的装配线后杂环化模式。我们的研究结果建立了氧的无处不在的铁载体异羟肟酸功能作为亲核试剂，并可能是N-O-C键形成在自然界中的一般策略的指示。
Nitrogen-heteroatom bonds figure prominently in the structural, chemical, and functional diversity of natural products. In the case of Pseudomonas siderophore pseudomonine, an N-O hydroxamate linkage is found uncommonly configured in an isoxazolidinone ring. In an effort to understand the biogenesis of this heterocycle, we have characterized the pseudomonine synthetase in vitro and reconstituted the complete biosynthetic pathway. Our results indicate that the isoxazolidinone of pseudomonine arises from spontaneous rearrangement of an oxazoline precursor. To the best of our knowledge, this is a previously uncharacterized mode of post-assembly line heterocyclization. Our results establish the oxygen of the ubiquitous siderophore hydroxamate functionality as a nucleophile and may be indicative of general strategy for N-O-C bond formation in nature.