Conformational analysis of small organic molecules using NOE and RDC data: A discussion of strychnine and α-methylene-γ-butyrolactone

To understand the properties and/or reactivity of an organic molecule, an understanding of its three-dimensional structure is necessary. Simultaneous determination of configuration and conformation often poses a daunting challenge. Thus, the more information accessible for a given molecule, the better. Additionally to (3)J-couplings, two sources of information, quantitative NOE and more recently also RDCs, are used for conformational analysis by NMR spectroscopy. In this paper, we compare these sources of conformational information in two molecules: the configurationally well-characterized strychnine 1, and the only recently configurationally and conformationally characterized alpha-methylene-gamma-butyrolactone 2. We discuss possible sources of error in the measurement and analysis process, and how to exclude them. By this means, we are able to bolster the previously proposed flexibility for these two molecules. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).