Determination of the Relative Configuration of a Five-Membered Lactone from Residual Dipolar Couplings

Thiele, Christina M.; Marx, Andreas; Berger, Robert; Fischer, J.; Biel, Markus; Giannis, Athanassios

doi:10.1002/anie.200503247

Cited by 83 publications

(73 citation statements)

References 61 publications

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“…Still, with the larger number of independent restraints available nowadays (distance, dihedral and orientational), this problem has become less severe and the faithful description of conformational ensembles is possible for favorable cases in cyclic systems [61] and even in open chain systems [58] .…”

Section: Namfis Deconvolution Analysismentioning

confidence: 99%

The Tubulin Binding Mode of MT Stabilizing and Destabilizing Agents Studied by NMR

Sánchez-Pedregal

Griesinger

2008

Topics in Current Chemistry

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Tubulin is a fascinating molecule that forms the cytoskeleton of the cells and plays an important role in cell division and trafficking of molecules. It polymerizes and depolymerizes in order to fulfill this biological function. This function can be modulated by small molecules that interfere with the polymerization or the depolymerization. In this article, the structural basis of this behavior is reviewed with special attention to the contribution of NMR spectroscopy. Complex structures of small molecules that bind to tubulin and microtubules will be discussed. Many of them have been determined using NMR spectroscopy, which proves to be an important method in tubulin research.

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Section: Namfis Deconvolution Analysismentioning

confidence: 99%

The Tubulin Binding Mode of MT Stabilizing and Destabilizing Agents Studied by NMR

Sánchez-Pedregal

Griesinger

2008

Topics in Current Chemistry

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“…The technique involves two steps: residual dipolar coupling (RDC)-enhanced NMR spectroscopy to enable the determination of the conformational ensemble and the relative configuration; [11,12] and subsequent prediction of ORD spectra by DFT calculations to differentiate between enantiomers. Combined, the two steps reveal the absolute configuration of a flexible molecule in solution.…”

Section: Introductionmentioning

confidence: 99%

Bijvoet in Solution Reveals Unexpected Stereoselectivity in a Michael Addition

Sun¹,

d’Auvergne²,

Reinscheid³

et al. 2011

Chemistry A European J

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The absolute configuration of small crystallizable molecules can be determined with anomalous X‐ray diffraction as shown by Bijvoet in 1951. For the majority of compounds that can neither be crystallized nor easily be converted into crystallizable derivatives, stereocontrolled organic synthesis is still required to establish their absolute configuration. In this contribution, a new fundamental methodology for resolving the absolute configuration will be presented that does not require crystallization. With residual dipolar coupling enhanced NMR spectroscopy, ensembles of a limited number of structures are created reflecting the correct conformations and relative configuration. Subsequently, from these ensembles, optical rotation dispersion (ORD) spectra are predicted by DFT calculations and compared to experimental results. The combination of these two steps reveals the absolute configuration of a flexible molecule in solution, which is a big challenge to chiroptical methods and DFT in the absence of NMR spectroscopy. Here the absolute stereochemistry of the product of a new Michael addition, synthesized via a niobium(V) chiral enolate, will be elucidated by using the new methodology.

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“…In this case, the conditions were rather special as the compound comprised an ensemble of two conformers of similar energy, nearly identical population and limited amplitude of flexibility for both possible diastereoisomers. 40 In general, the use of this approach should be avoided! A similar approach, however, can be used for interpretation of RDCs obtained from functional groups exhibiting fast conformational reorientation such as methyl-, tert-butyl-, or phenyl-groups making it possible to treat them as an averaged entity with respect to their RDCs.…”

Section: Averaged Structuresmentioning

confidence: 99%

Determining the Stereochemistry of Molecules from Residual Dipolar Couplings (RDCs)

Böttcher

Thiele

2012

Encyclopedia of Magnetic Resonance

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Residual dipolar couplings (RDCs) have recently revolutionized the structure determination of biological macromolecules by NMR spectroscopy. Their utility in the structure determination of small/medium-sized organic compounds is more and more recognized. The questions arising in organic compounds are completely different from biomolecular NMR. Especially, the determination of the stereochemistry (relative configuration and diastereotopic assignments) is the focus of this article. A short overview on how to introduce the anisotropic environment necessary to measure RDCs and the applications for the determination of relative configurations in rigid and moderately flexible compounds are given together with the description of the theoretical background for interpreting the data. Since the area of alignment media for organic compounds and the applications to flexible compounds are developing extremely fast, this article can be viewed as momentary picture only.

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Determination of the Relative Configuration of a Five-Membered Lactone from Residual Dipolar Couplings

Abstract: The determination of the relative configuration of stereogenic centers in organic molecules by NMR spectroscopy is in general an interlinked problem of simultaneous determination of conformation and configuration. This is usually accomplished using distance restraints from NOE data [1]

Cited by 83 publications

References 61 publications

The Tubulin Binding Mode of MT Stabilizing and Destabilizing Agents Studied by NMR

The Tubulin Binding Mode of MT Stabilizing and Destabilizing Agents Studied by NMR

Bijvoet in Solution Reveals Unexpected Stereoselectivity in a Michael Addition

Determining the Stereochemistry of Molecules from Residual Dipolar Couplings (RDCs)

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