NMR structural characterization from one‐bond ¹³C¹³C couplings: Complete assignment of a hydrogen‐poor depsidone

Abstract

The connectivity, conformation, tautomeric form, and dynamics of a new depsidone (perisalazinic acid) were characterized using one-bond 13 C 13 C NMR scalar couplings (1 J CC) obtained from the INADEQUATE experiment. Characterization of perisalazinic acid using more conventional NMR techniques is problematic due to the extremely limited number of C H protons present. In the present study, 81 candidate structures were considered and a best fit structure was selected by comparing computed 1 J CC values for each candidate to 15 experimental values. Of the six flexible moieties in perisalazinic acid, three are adequately represented by a single orientation stabilized by intramolecular hydrogen bonding. The three remaining groups are present as mixtures of conformers with two sites consisting of a pair of conformations and another disordered over six orientations. This study demonstrates the feasibility of complete three-dimensional structural characterization of an unknown using only theoretical and experimental 1 J CC values.

Crews' rule—Still useful but often misquoted

“…This error has propagated through the literature [9][10][11][12][13][14][15][16][17][18] and continues to do so to this day. [19][20][21] This is rather surprising as Crews' rule is normally cited in the context of solving the structures of protondeficient molecules. To those familiar with calculating double-bond equivalents, the value of 2 should be suspiciously high.…”

Computational1H and13C NMR in structural and stereochemical studies

“…For details, see original publication. Reproduced with minor editing privilege from Sestile, et al [ 364 ] with the permission of John Wiley and Sons…”

“…Another example deals with the elucidation of connectivity, conformation, tautomeric form, and dynamics of a new depsidone, perisalazinic acid (81), by using onebond carbon-carbon coupling constants, as reported by Sestile, et al [364] Characterization of perisalazinic acid using conventional NMR techniques was not possible due to the extremely limited number of protons in the polycyclic framework. In that study, as many as 81 candidate structures were considered, and a best fit structure was selected by comparing computed 1 J CC values for each candidate to 15 experimental values, as illustrated in Figure 37.…”

“…For details, see original publication. Reproduced with minor editing privilege from Sestile, et al [364] with the permission of John Wiley and Sons Molecular docking studies were further performed to investigate the effects of these ligands on M3CLpro and to provide insights into the chemical environment of the ligand-binding site. Results of that study were offered as a potential guide for the design of possible potent protease inhibitors and the aid in coping with the COVID-19 pandemic.…”