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

Abstract

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 α-methylene-γ-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.

The Role of Hyperconjugation on the Structure and C–H Stretching Frequencies of 3,3′-Ethane-1,2-diyl- bis-1,3,5-triazabicyclo[3.2.1]octane (ETABOC): An X-Ray Structure and Vibrational Study

“…If we consider the C i conformer (5) instead of the C 2V conformer (3), in which the N3 and N11 lone pairs adopt an endo arrangement, the possibility to observe chemical equivalence between the signals must include a free rotation of both bicyclic rings around the central ethylene moiety at room temperature. However, the observed NOE effect indicates that the molecule is stiff because this effect is largely based on through-space dipolar interactions between two spins [23][24][25].…”

High-pressure NMR spectroscopy in studies of the conformational composition of small molecules in supercritical carbon dioxide

“…Therefore, developing approaches to control the conformational ensembles of molecules in a supercritical solvent is very important. A significant progress in studies of conformational state of molecules of biologically active compounds has been achieved recently using NMR spectroscopy [7][8][9][10][11][12][13][14][15][16] and vibrational spectroscopy [17][18][19][20][21][22][23].. A correlation between the distribution of the conformers of ibuprofen in supercritical carbon dioxide and fraction of the polymorphs arising in supercritical sedimentation has been found with the aid of vibrational spectroscopy and MD simulations [20]. This example shows clearly that vibrational spectroscopy can give information on the conformational manifolds of small molecules which would be in a good agreement with MD simulations.…”

Conformational Analysis of an Antibacterial Cyclodepsipeptide Active against Mycobacterium tuberculosis by a Combined ROE and RDC Analysis

“…We have previously used the combination of NOE/ROE and RDC data for the investigationo ft he solutions tructure (including conformer populations for flexible compounds) of small organic compounds,p hotoswitchable compounds, and very recently,a lso of ah ighly efficient peptidec atalystu sed in kinetic resolution. [20][21][22][23] Although, for the former cases, the approach of probingc alculated structures with NMR data (NOE/ROE and RDC) was successful andc onformer ensemblest hat were in accordancew ith NOE/ROE and RDC data could be obtained with reasonable effort, the situation was more complicated for the peptidec atalyst. Am anualr efinement procedure, which involved as tep-wise construction procedure, had to be used to obtain an ensemble of conformers that was in accordance with both ROE and RDC data.…”