Computer‐Assisted 3D Structure Elucidation of Natural Products using Residual Dipolar Couplings

Abstract

An enhanced computer-assisted procedure for the determination of the relative configuration of natural products, which starts from the molecular formula and uses a combination of conventional 1D and 2D NMR spectra, and residual dipolar couplings (RDCs), is reported. Having already the data acquired (1D/2D NMR and RDCs), the procedure begins with the determination of the molecular constitution using standard computer-assisted structure elucidation (CASE) and is followed by fully automated determination of relative configuration through RDC analysis. In the case of moderately flexible molecules the simplest data-explaining conformational model is selected by the use of the Akaike information criterion.

Measurement of residual chemical shift anisotropies in compressed polymethylmethacrylate gels. Automatic compensation of gel isotropic shift contribution

“…The estimated and optimized scaling factors c increased as expected being now 0.119 and 0.281, respectively. Our second test molecule 10-epi-8-deoxycumambrin B (2), [40] which has already previously been the target of an RDC analysis, [8,41] has one more stereogenic center than α-santonin 1, leading therefore to 16 possible diastereomers. The different configurations of 2 will be named after descriptors R/S at positions C1, C5, C6, C7, and C10.…”

“…RDCs encode for the relative orientation of internuclear vectors (e.g., CH bonds) with respect to the alignment tensor regardless of the distance between them. Hence, RDCs can be employed for determination of the relative configuration even in the presence of some degree of molecular flexibility . In an analogous way, the orientation between the principal axis system of chemical shielding tensors relative to the alignment tensor can be determined by measurement of residual chemical shift anisotropies (RCSAs).…”

“…Hence, RDCs can be employed for determination of the relative configuration even in the presence of some degree of molecular flexibility. [4][5][6][7][8] In an analogous way, the orientation between the principal axis system of chemical shielding tensors relative to the alignment tensor can be determined by measurement of residual chemical shift anisotropies (RCSAs). However, chemical shielding tensors, differently from the dipolar coupling ones, have an isotropic part, and therefore, measurement of RCSAs necessitates two different alignment conditions.…”

A review on the latest advances in extraction and analysis of artemisinin

“…After the 13 C‐NMR empirical chemical shift prediction, the first scored structure, as shown in Figure , was obtained. The next step involved feeding of 2D SDF file into the previously published Python programme, which encapsulated the diastereoisomer generation and conformational search steps, followed by the development of new scripts to automatically launch the density functional theory (DFT) chemical shift computations. Because of the geometrical hindrance created by the peroxide ring, only 32 diastereoisomers from possible 64 could be obtained.…”

Isotropic/Anisotropic NMR Editing by Resolution‐Enhanced NMR Spectroscopy

“…Very recently,t he benefits to combining computer-assisted structural elucidation( CASE)p rograms and density functional theory( DFT) calculations in exclusive concert with RDCs and/or RCSAs opens exciting perspectives for the automatic and efficient structurald iscrimination of challenging molecular structures without the need of the classical scalar J couplings or NOEs. [14][15][16] In contrastt ot he isotropic (iso) J andc hemical shifts (d iso ), anisotropic (aniso)R DCs and RCSAs constraints show as trongd ependence on the type, nature,a nd level of molecular alignment of the sample to be analysed, and therefore their accurate determination and reproducibility represent an important,challenging task.Experimentally,t he magnitude and, above all,t he signo f RDCs or RCSAs can be determined by comparing two independentm easurements in two separate isotropic versusa nisotropic samples or at two different alignment conditions. Ap rimary experimental concern is the equivalence between the iso…”