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Residual dipolar couplings (RDCs) have become a powerful tool for the determination of relative configurations in natural products and they have already helped to elucidate structures where more traditional techniques, such as the nuclear Overhauser effect or scalar coupling analysis, have generated ambiguous answers. This chapter is a critical review that intends to help the reader along all of the steps involved in RDC analysis, from choosing the right alignment media and pulse sequences to the computational analysis of the data. Several scenarios for data analysis are discussed based on the degree of mobility of the molecules being studied. Finally, illustrative examples of the application of the technique to the structure elucidation of natural products are discussed.

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