A DMSO‐Compatible Orienting Medium: Towards the Investigation of the Stereochemistry of Natural Products

Abstract

The elucidation of the relative stereochemistry of asymmetric centers of organic molecules is an important challenge in chemistry since it requires the simultaneous determination of conformation and configuration. Whereas conventional NMR spectroscopy parameters such as NOE and 3 J coupling constants, which provide internuclear distances and dihedral angles, yield the configuration of stereocenters in rigid compounds, this approach is difficult or impossible in cases in which the molecule is flexible or the stereocenters are remote in the bonding network. Residual dipolar couplings (RDCs) provide additional structural restraints, as has been abundantly shown in structural biology, [1] and might enhance the power of NMR spectroscopy in the determination of the conformation and configuration of small organic molecules at the same time. They rely on the weak alignment of molecules in solution and provide angular as well as distance information that are not contained in the NOE or J coupling values. RDCs have proven to be very efficient in the stereochemical assignment of moieties and hold promise as parameters for the determination of the stereochemistry, even in nonrigid molecules.

Simultaneous Determination of the Conformation and Relative Configuration of Archazolide A by Using Nuclear Overhauser Effects, J Couplings, and Residual Dipolar Couplings

“…[21] The structure calculations were set up for the 64 different relative diastereoisomers of ArcA. The NOE-and J-coupling-derived restraints were imposed by using the "RELAXATION" [24] and "DIHEDRAL" [25] modules of the XPLOR-NIH Ver.…”

“…[21] The quality of the fit (Q) was evaluated as a normalized root mean square deviation (rmsd) against the measured RDCs. [22] The conformations obtained from the Jcoupling and NOE restraints were not refined versus the RDCs prior to fitting.…”

Synthesis and Biological Properties of Cylindramide Derivatives: Evidence for Calcium‐Dependent Cytotoxicity of Tetramic Acid Lactams

“…We recalculated the structure of cylindramide 1 on the basis of newly measured residual dipolar couplings (RDCs) that provide information about the long-range structure of the cyclic structure. [20] For cylindramide 1, the overall curvature of the macrolactam ring can especially be improved. For the measurement of RDCs, cylindramide 1 was dissolved in DMSO and the solution was placed on top of a polyacrylonitrile gel that had been swollen in DMSO.…”

Structure Refinement of Cyclosporin A in Chloroform by Using RDCs Measured in a Stretched PDMS‐Gel

“…For these media, a workaround is provided by variable-angle sample spinning [12] if a high-resolution magic-angle spinning probe head is available. On the other hand, stretched polymer-gel-based alignment media, as introduced recently for apolar [13,14] and polar [15,16] organic solvents, are easily scalable with respect to their alignment properties, as they have no lower anisotropy limit. Among these polymer gels, poly(dimethylsiloxane) cross-linked by accelerated electrons and swollen in apolar organic solvents has the most interesting NMR properties, as it shows only a single 1 H NMR signal at % 0.1 ppm and therefore interferes only minimally with the signals of interest.…”