Assignment of complex molecular structures from nuclear magnetic resonance (NMR) data can be prone to interpretational mistakes. Residual dipolar couplings (RDCs) and residual chemical shift anisotropy (RCSA) provide a spatial view of the relative orientations between bonds and chemical shift shielding tensors respectively, regardless of separation. Consequently, these data constitute an excellent reporter of global structural validity. Anisotropic NMR parameters can be used to evaluate investigators’ structure proposals or structures generated by Computer-Aided Structure Elucidation (CASE). Application of the method to several complex structure assignment problems shows promising results that signal a potential paradigm shift from conventional NMR data interpretation, of particular utility for compounds not amenable to x-ray crystallography.
The revision of the structure of
the sesquiterpene aquatolide from
a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling
NMR data, X-ray crystallography, and the recent confirmation via full
synthesis exemplify that the achievement of “structural correctness”
depends on the completeness of the experimental evidence. Archived
FIDs and newly acquired aquatolide spectra demonstrate that archiving
and rigorous interpretation of 1D 1H NMR data may enhance
the reproducibility of (bio)chemical research and curb the growing
trend of structural misassignments. Despite being the most accessible
NMR experiment, 1D 1H spectra encode a wealth of information
about bonds and molecular geometry that may be fully mined by 1H iterative full spin analysis (HiFSA). Fully characterized
1D 1H spectra are unideterminant for a given structure.
The corresponding FIDs may be readily submitted with publications
and collected in databases. Proton NMR spectra are indispensable for
structural characterization even in conjunction with 2D data. Quantum
interaction and linkage tables (QuILTs) are introduced for a more
intuitive visualization of 1D J-coupling relationships,
NOESY correlations, and heteronuclear experiments. Overall, this study
represents a significant contribution to best practices in NMR-based
structural analysis and dereplication.
Due to their well-defined three-dimensional geometry, spiro compounds are widely utilized in drug research. From the central tetrahedral carbon atom, besides the regular structure, an inverted spiro connectivity may be envisioned. Here we disclose the synthesis of this molecule class that we have coined quasi[1]catenanes. Next to their fascinating and aesthetic shape, the higher compactness as compared to regular spiro bicycles is noteworthy. To enable synthetic access to compact entangled multimacrocyclic molecules, we have developed a new strategy. The key element is a template, which is covalently connected to the linear precursors, and spatially directs the sterically congested backfolding macrocyclizations that are required to give quasi[1]catenanes. Similarly, quasi[1]rotaxanes are made.
The 13C nmr spectra of oxazole and eight mono- and disubstituted derivatives have been analyzed with regard to the chemical shifts and the various carbon–proton coupling constants of the ring carbons. The data of the parent oxazole are compared with thiazole and 1-methylimidazole.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.