Regiochemical Tagging: A New Tool for Structural Characterization of Isomeric Components in Combinatorial Mixtures

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• 作者：Noureddin Nazarpack-Kandlousy ; Igor V. Chernushevich ; LingJie Meng ; Ying Yang ; and Alexey V. Eliseev
• 刊名：Journal of the American Chemical Society
• 出版年：2000
• 出版时间：April 12, 2000
• 年：2000
• 卷：122
• 期：14
• 页码：3358 - 3366
• 全文大小：117K
• 年卷期：v.122,no.14(April 12, 2000)
• ISSN：1520-5126

文摘

In this contribution we present a new combined synthetic and analytical strategy (regiochemicaltagging) that allows facile determination of complete structure, including substituent position and regiochemistry,of mass-redundant components in complex combinatorial mixtures. The libraries of components (oxime ethers)are formed by the reaction of a mixture of substituents (aldehydes) with a scaffold containing several chemicallysimilar attachment points (aminooxy groups). The structure of the resulting library components can then bedetermined from a combination of single MS and the tandem (MS/MS) spectra. Determination of the uniqueisomeric motif for each component is made possible via the following features of library design: (1) part ofthe scafforld moiety, "transferable group" (the nitrogen atom from the oxime group) is transferred to thesubstituent during fragmentation in the tandem experiment, (2) transferable groups on the scaffold differ fromeach other by either isotopic labels or fragmentation energies, and (3) mass-redundant substituents are isotopicallylabeled to create at least a 2 mass unit difference between them. The components of the resulting library thusbecome labeled with different mass- and energy tags, which allows for precise regiochemical assignment ofthe functional group positions on the scaffold and substituents by mass spectrometry. The approach has beenused to create and analyze a mixture of 27 isomeric compounds, each containing three boronic acid groups.The combination of the MS and MS/MS spectra of the tagged mixture has yielded a unique and structurallydefinitive signature of each component. Applications of the regiochemical tagging techniques to rapid synthesisand screening of combinatorial mixtures are discussed.