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NMR and molecular mechanics studies on the solution‐state conformation of (−)‐scopolamine free base
Author(s) -
Glaser Robert
Publication year - 1993
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1260310405
Subject(s) - chemistry , diastereomer , moiety , homonuclear molecule , protonation , heteronuclear molecule , conformational isomerism , stereochemistry , alkane stereochemistry , chemical shift , nuclear overhauser effect , proton nmr , crystallography , free base , quinuclidine , nuclear magnetic resonance spectroscopy , molecule , crystal structure , organic chemistry , ion , salt (chemistry)
The NMR parameters of (−)‐scopolamine free base in CDCl 3 determined by Sarazin et al. were used to reevaluate some of the stereochemical conclusions recently reported by the authors. Similarly to the case with the protonated salt, the major contributor to the fast exchange limit time‐averaged structure of the free base tropate ester moiety appears to be the rotamer in which the phenyl and hydroxyl groups are antiperiplanar. Long‐range heteronuclear coupling constants for the carboxyl carbon and also for the aromatic ipso carbon have been reassigned. Vicinal homonuclear coupling constants involving the methine proton and the two internally diastereotopic protons in the ( S )‐CHCH 2 OH moiety have also been reassigned. Four conformational archetypes were calculated by molecular mechanics for the (−)‐(N s ,Cα‐ S )‐scopolamine free base equatorial N ‐methyl diastereomer based on x‐ray crystallographically determined scopolamine structural analogues. The degree of anisochronicity (and their relative shifts) exhibited by the internally diastereotopic oxiranyl protons and carbons and the observation of NOE intensity enhancement of oxiranyl protons upon {H‐aromatic} can be interpreted as arising from an interconverting profile of conformations at the fast exchange limit. While a conformation similar to that of the solid‐state hydrobromide sesquihydrate salt appears to be a major contributor to the time‐averaged structure, other conformations can also play minor roles.