Structure Revision of the Lomaiviticins.
Structure Revision of the Lomaiviticins.
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DOI：
10.1021/jacs.1c01729
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发表时间：
2021-05-05
影响因子：
15
通讯作者：
Herzon SB
中科院分区：
文献类型：
--
作者：
Kim LJ;Xue M;Li X;Xu Z;Paulson E;Mercado B;Nelson HM;Herzon SB
洛麦替星是含有不常见的重氮环戊二烯官能团和2-4个脱氧糖苷残基的二聚遗传毒性代谢物。由于单体苷元单元中的19个碳原子中只有6个是质子连接的，因此通过NMR光谱分析确定其结构是困难的。先前的结构解析工作确定了洛麦替星的两半通过附加到氧化的环己烯酮环的单个碳-碳键连接。该环被认为包含4，5-二羟基环己-2-烯-1-酮。桥接键位于C6。尚未对该结构方案进行测试，因为尚未通过全化学合成制备洛麦替星或通过X射线晶体学成功分析洛麦替星。在这里，我们公开了microED研究，其确定（-）-洛梅葡萄素C含有4，6-二羟基环己-2-烯-1-酮残基，桥接碳-碳键位于C5，并且环己烯酮环的取向和次级糖苷的构型相对于它们的原始分配是颠倒的。高场（800 MHz）NMR分析支持修订后的分配，并表明早期的努力被误导的组合接近零的3 JH 4，H5耦合常数和4JC，H耦合解释为3 JC，H耦合。预期的13 C化学位移和C-H耦合常数的DFT计算提供了进一步的结构修订的强大支持。由于已证明洛麦替星A、B和C的相互转化，因此这些发现适用于每种分离株。这些研究阐明了这个代谢产物家族的结构，并强调了microED分析在天然产物结构测定中的作用。
The lomaiviticins are dimeric genotoxic metabolites that contain unusual diazocyclopentadiene functional groups and 2–4 deoxyglycoside residues. Because only 6 of 19 carbon atoms in the monomeric aglycon unit are proton-attached, their structure determination by NMR spectroscopic analysis is difficult. Prior structure elucidation efforts established that the two halves of the lomaiviticins are joined by a single carbon–carbon bond appended to an oxidized cyclohexenone ring. This ring was believed to comprise a 4,5-dihydroxycyclohex-2-ene-1-one. The bridging bond was positioned at C6. This structure proposal has not been tested because no lomaiviticin has been prepared by total chemical synthesis or successfully analyzed by X-ray crystallography. Here, we disclose microED studies which establish that (−)-lomaiviticin C contains a 4,6-dihydroxycyclohex-2-ene-1-one residue, that the bridging carbon–carbon bond is located at C5, and that the orientation of the cyclohexenone ring and configuration of the secondary glycoside are reversed, relative to their original assignment. High-field (800 MHz) NMR analysis supports the revised assignment and suggests earlier efforts were misled by a combination of a near-zero 3JH4,H5 coupling constant and a 4JC,H coupling interpreted as a 3JC,H coupling. DFT calculations of the expected 13C chemical shifts and C–H coupling constants provide further robust support for the structure revision. Because the interconversion of lomaiviticins A, B, and C has been demonstrated, these findings apply to each isolate. These studies clarify the structures of this family of metabolites and underscore the power of microED analysis in natural product structure determination.
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影响因子：
5.2
作者：
Morris, William J.;Shair, Matthew D.
通讯作者：
Shair, Matthew D.
影响因子：
15
作者：
He, HY;Ding, WD;Carter, GT
通讯作者：
Carter, GT
影响因子：
2.1
作者：
Janso, Jeffrey E.;Haltli, Brad A.;Eustaquio, Alessandra S.;Kulowski, Kerry;Waldman, Abraham J.;Zha, Li;Nakamura, Hitomi;Bernan, Valerie S.;He, Haiyin;Carter, Guy T.;Koehn, Frank E.;Balskus, Emily P.
通讯作者：
Balskus, Emily P.
影响因子：
16.6
作者：
Krygowski, Evan S.;Murphy-Benenato, Kerry;Shair, Matthew D.
通讯作者：
Shair, Matthew D.
影响因子：
18.3
作者：
Herzon SB
通讯作者：
Herzon SB