Conformational pseudopolymorphism and solid-state CPMAS NMR studies for determination of solvent-dependent solution-state conformational preferences for (-)-scopolamine hydrobromide/hydrochloride salts

Robert Glaser, Dror Shiftan, Marc Drouin

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21 Scopus citations

Abstract

Crystalline (-)-scopolamine hydrohalide (bromide and chloride) salts exist in two conformational families for the tropate ester moiety: the compact conformation (hydrates, phenyl ring underneath the scopine moiety), and the extended conformation (anhydrates, phenyl ring ca antiperiplanar to oxiranyl O-atom). CPMAS 13C NMR solid-state spectra of anhydrates and hydrates are different. In both tertiary and quaternary scop olammonium salts, phenyl rings are immobile in compact conformation crystals having ca. 2.5 Å close lateral neighbors on both faces of the planar moiety. Phenyl rings undergo a π-flip in extended conformation crystals having ca. 3.0 Å close lateral neighbors on either face of the aromatic plane. Due to different O=C-Cα-CH2OH dihedral angles [synperiplanar (eclipsed, in compact) and (+)-synclinal (gauche, in extended)], the methylol carbon chemical shifts of crystalline tertiary and quaternary scopolammonium salts and analogues are diagnostic markers for the tropate ester solid-state conformation [δCH2OH downfield from alkoxy δC(3) for extended conformations and upfield of δC(3) in compact conformations]. These solid- state model Δδ relationships were used to deconvolute weighted time- averaged chemical shifts in different solvents: e.g., one axial N-methyl scopolammonium bromide phenyl-ring face is solvent exposed in the compact conformation predominating in D2O medium, while both faces are solvent accessible in the extended major conformational contributor in CD2Cl2 solution.

Original languageEnglish
Pages (from-to)9217-9224
Number of pages8
JournalJournal of Organic Chemistry
Volume64
Issue number25
DOIs
StatePublished - 10 Dec 1999

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