Journal of Organic Chemistry 2004-10-29

Simultaneous assignment of all diastereotopic protons in strychnine using RDCs: PELG as alignment medium for organic molecules.

Christina M Thiele

Index: J. Org. Chem. 69 , 7403-7413, (2004)

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Abstract

The concept of using residual dipolar couplings (RDCs) for the structure determination of organic molecules is applied to the simultaneous assignment of all diastereotopic protons in strychnine. To use this important NMR parameter the molecule has to be aligned in the magnetic field. Here we present a new alignment medium for organic substrates. The optimization of the alignment properties of mixtures of poly-gamma-ethyl-L-glutamate (PELG) and CDCl(3) are described and the alignment properties of PELG at different concentrations are evaluated. A comparison of PELG with poly-gamma-benzyl-L-glutamate (PBLG) shows considerable differences in the magnitude of alignment for strychnine in the two alignment media. PELG induces a lower degree of order and makes the measurement of residual dipolar couplings (RDCs) in strychnine possible. All one-bond C-H RDCs of strychnine in PELG were determined by using 2D heteronuclear single quantum coherence (HSQC) spectroscopy. The strategy for the extraction of RDCs for methylene groups is described in detail. The RDCs and order parameters are used to assign pairs of diastereotopic protons. This methodology can distinguish not only one pair of diastereotopic protons but it can be used to assign all pairs of diastereotopic protons simultaneously. Two different calculation approaches to achieve this task are described in detail.