Relative configuration of micrograms of natural compounds using proton residual chemical shift anisotropy

Abstract

3D molecular structure determination is a challenge for organic compounds or natural products available in minute amounts. Proton/proton and proton/carbon correlations yield the constitution. J couplings and NOEs oftentimes supported by one-bond 1H,13C residual dipolar couplings (RDCs) or by 13C residual chemical shift anisotropies (RCSAs) provide the relative configuration. However, these RDCs or carbon RCSAs rely on 1% natural abundance of 13C preventing their use for compounds available only in quantities of a few 10’s of µgs. By contrast, 1H RCSAs provide similar information on spatial orientation of structural moieties within a molecule, while using the abundant 1H spin. Herein, 1H RCSAs are accurately measured using constrained aligning gels or liquid crystals and applied to the 3D structural determination of molecules with varying complexities. Even more, deuterated alignment media allow the elucidation of the relative configuration of around 35 µg of a briarane compound isolated from Briareum asbestinum.

Absolute configuration by vibrational circular dichroism of anti-inflammatory macrolide briarane diterpenoids from the Gorgonian Briareum asbestinum

“…The absolute determination of 1 by VCD and XRD is in agreement with a very recent 1 H residual chemical shift anisotropy measurement 41 , a powerful contemporary methodology for the study of molecular structures 42 .…”

Study and quantification of the enantiodiscrimination power of four polymeric chiral LLCs using NAD 2D-NMR

“…This approach provides a more insightful and reliable comparison of EDAs. In practice, this description is achieved by calculating the molecular Saupe matrix of each enantiomer, {S ab } R,S , derived from three types of NMR interactions: 22,23 (i) the residual chemical shift anisotropies (RCSAs); [29][30][31][32] (ii) the residual dipolar couplings (RDCs); [33][34][35][36][37][38] and (iii) the residual quadrupolar couplings (RQCs) of nuclei with spin quantum number I 4 1 2 as deuterium (I = 1). 39,40 These matrices can be then compared by calculating the generalized 9D b angle (eqn (2)), or its cosine value (GCB value).…”

Single experiment measurement of residual dipolar couplings in aqueous solution using a biphasic bisperylene imide chromonic liquid crystal

“…NMR in weakly aligned media has become a firmly established tool for structural elucidation of organic compounds. [1][2][3] Although most applications to structural elucidation problems involved the use of residual dipolar couplings (RDCs), [4,5] mostly one-bond proton-carbon 1 D CH ones, residual chemical shift anisotropies (RCSAs), [6,7] and even 2 H residual quadrupolar couplings (RQCs) [8] have come recently into play.…”