Trapping‐Enrichment Multi‐dimensional Liquid Chromatography with On‐Line Deuterated Solvent Exchange for Streamlined Structure Elucidation at the Microgram Scale

Abstract

At the forefront of chemistry and biology research, development timelines are fast‐paced and large quantities of pure targets are rarely available. Herein, we introduce a new framework, which is built upon an automated, online trapping‐enrichment multi‐dimensional liquid chromatography platform (TE‐Dt‐mDLC) that enables: 1) highly efficient separation of complex mixtures in a first dimension (1D‐UV); 2) automated peak trapping‐enrichment and buffer removal achieved through a sequence of H2O and D2O washes using an independent pump setup; and 3) a second dimension separation (2D‐UV‐MS) with fully deuterated mobile phases and fraction collection to minimize protic residues for immediate NMR analysis while bypassing tedious drying processes and minimizing analyte degradation. Diverse examples of target isolation and characterization from organic synthesis and natural product chemistry laboratories are illustrated, demonstrating recoveries above 90 % using as little as a few micrograms of material.

Small‐scale two‐dimensional liquid chromatography for a preparative re‐purification of a highly labile tritium‐labeled compound

“…purifications with solvent exchange for NMR. 9 Another possibility is to use trapping cartridges as an interface. 10 A third option is the direct transfer, with or without modulation, from the first separation column to the second separation column.…”