Oligopeptide (FK)4facilitates the determination of the absolute stereochemistry of chiral organic compoundsviaNMR Spectroscopy

Abstract

ABSTRACTMolecular chirality plays a crucial role in the fields of chemistry and biology. Various nuclear magnetic resonance (NMR) methods have been employed for assignment of stereochemical configurations. Alignment media for measurements of anisotropic parameters contribute to configuration elucidations, while chiral auxiliaries assist in enantiomer discrimination and chiral recognition. However, each method comes with limitations, and the assignment of absolute configuration by NMR remains challenging. In this study, we explored a combined approach for absolute configuration elucidation with the multifaceted application of the oligopeptide (FK)4, which possesses dual functionalities as an alignment medium for anisotropic NMR measurements and a chiral differentiating agent. As an alignment medium, (FK)4facilitates the analysis of stereochemical features through residual dipolar couplings (RDC), aiding in the structural elucidation of stereoisomers. Moreover, (FK)4exhibits unique chiral differentiating properties, interacting distinctly with enantiomers and resulting in observable bifurcation of chemical shift signals, in13C,1H and19F spectra. Using isoleucine and xylose as model compounds, we demonstrate how the dual functionality of (FK)4enables the identification of stereoisomeric structuresviaRDC parameters and the assignment of enantiomeric configurations through measurements of t2 relaxation time coupled with theoretical simulations. These findings highlight the potential of versatile chiral media as (FK)4for approaching the elucidation of absolute configurations of organic moleculesviacombined NMR spectroscopy approaches, with implications for structural characterization and enantiomer discrimination in chemical applications.