Screening of chiral shift reagents suitable to generically separate the enantiomers of V-agents by 31P-NMR spectroscopy,Toxicology Letters

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Screening of chiral shift reagents suitable to generically separate the enantiomers of V-agents by 31P-NMR spectroscopy
Toxicology Letters ( IF 2.9 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.toxlet.2019.12.004
Marianne Koller ₁ , Horst Thiermann ₁ , Franz Worek ₁

Affiliation

Fourteen amino acids protected at the N-terminal and at their side chains were screened for resolving the enantiomers of V-agents by NMR. While none of the shift reagents tested showed really effective separation in proton NMR, two of them (BOC-Gln(Xan)-OH, 16, and Z-Arg(Z)2-OH), 21, with 16 superior to 21) were found suitable to separate the enantiomers of all V-agent homologues involved in the test by 31P-NMR. Molar ratios investigated were 1:0.5, 1:1, 1:1.5, 1:2, and 1:3 with the V-agent set to 1 throughout the experiments. All these ratios were more or less effective, but 1:3 was found to separate the V-agents the most reliable way. It is postulated that three chiral solvating molecules are then coordinated around the organophosphate: ion pair formation with the amino nitrogen of the V agent side chain, hydrogen bonding provided by the PO unit, and extension of coordination at the phosphorus atom itself. After chiral separation of VX by semi-preparative LC-MS the enantiomers were examined with both configurations of 16 releasing four different 31P NMR peaks which correspond to four different complexes: R-S3, R-R3, S-R3, and S-S3. Comparing these results with literature data it is assumed that (+)-VX corresponds to the RP configuration and (-)-VX to the SP-configuration.

中文翻译：

用 31P-NMR 光谱法筛选适用于一般性分离 V-剂对映体的手性位移试剂

筛选了在 N 端及其侧链受保护的 14 个氨基酸，用于通过 NMR 解析 V 试剂的对映异构体。虽然测试的移位试剂均未在质子 NMR 中显示真正有效的分离，但其中两种（BOC-Gln(Xan)-OH, 16 和 Z-Arg(Z)2-OH), 21，其中 16 优于 21）发现适用于通过 31 P-NMR 分离测试中涉及的所有 V-agent 同系物的对映异构体。研究的摩尔比为 1:0.5、1:1、1:1.5、1:2 和 1:3，在整个实验中 V-agent 设置为 1。所有这些比率或多或少都有效，但发现 1:3 是分离 V-agent 的最可靠方式。假设三个手性溶剂化分子随后在有机磷酸酯周围配位：与 V 剂侧链的氨基氮形成离子对，由 PO 单元提供氢键，以及磷原子本身的配位扩展。通过半制备型 LC-MS 对 VX 进行手性分离后，对映异构体进行了检查，16 的两种构型释放了四个不同的 31P NMR 峰，对应于四种不同的复合物：R-S3、R-R3、S-R3 和 S-S3 . 将这些结果与文献数据进行比较，假设 (+)-VX 对应于 RP 配置，而 (-)-VX 对应于 SP 配置。

更新日期：2020-03-01

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