TY - JOUR
T1 - Solution- and solid-state stereochemistry of (-)-α-lobeline hydrochloride and hydrobromide, a respiratory-stimulant drug
AU - Glaser, Robert
AU - Hug, Paul
AU - Drouin, Marc
AU - Michel, André
PY - 1992/12/1
Y1 - 1992/12/1
N2 - The solid-state structure of (-)-α-lobeline hydrobromide has been determined by single crystal X-ray diffraction analysis. (-)-α-Lobeline hydrobromide gives crystals belonging to the orthorhombic P212 121 space group, and at 298 K: a = 6.0100(3), b = 11.7177(4), c = 28.977(2) Å, V = 2040.7(2), Z = 4, R(F) = 0.030, and Rw(F) = 0.022. The (2R,6S,CBS)-absolute configuration was determined from the effects of anomalous dispersion of the bromine atom. The N-methyl group exists in an axial configuration similar to that previously described for the hydrochloride salt. However, in the hydrobromide salt the β-hydroxyphenethyl residue exhibits a different conformation from that noted for the hydrochloride salt. 1H and 13C NMR spectroscopy for the hydrochloride salt dissolved in CD2Cl 2 shows axial- and equatorial-N-methyl solution-state diastereoisomers in the ratio ca. 5:1, respectively. The major contributors to the time-averaged structures of the salt in D2O and the free base in CDCl3 also show axial N-methyl orientations. Conformational differences for the acetophenonyl and β-hydroxyphenethyl moieties were found in the two N-methyl epimers, as well as in the time-averaged salt (D 2O) and free base (CDCl3) structures. The putative bioactive conformation of the nicotine agonist was found to have a different acetophenonyl arm conformation than that found in both crystals.
AB - The solid-state structure of (-)-α-lobeline hydrobromide has been determined by single crystal X-ray diffraction analysis. (-)-α-Lobeline hydrobromide gives crystals belonging to the orthorhombic P212 121 space group, and at 298 K: a = 6.0100(3), b = 11.7177(4), c = 28.977(2) Å, V = 2040.7(2), Z = 4, R(F) = 0.030, and Rw(F) = 0.022. The (2R,6S,CBS)-absolute configuration was determined from the effects of anomalous dispersion of the bromine atom. The N-methyl group exists in an axial configuration similar to that previously described for the hydrochloride salt. However, in the hydrobromide salt the β-hydroxyphenethyl residue exhibits a different conformation from that noted for the hydrochloride salt. 1H and 13C NMR spectroscopy for the hydrochloride salt dissolved in CD2Cl 2 shows axial- and equatorial-N-methyl solution-state diastereoisomers in the ratio ca. 5:1, respectively. The major contributors to the time-averaged structures of the salt in D2O and the free base in CDCl3 also show axial N-methyl orientations. Conformational differences for the acetophenonyl and β-hydroxyphenethyl moieties were found in the two N-methyl epimers, as well as in the time-averaged salt (D 2O) and free base (CDCl3) structures. The putative bioactive conformation of the nicotine agonist was found to have a different acetophenonyl arm conformation than that found in both crystals.
UR - http://www.scopus.com/inward/record.url?scp=37049082127&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:37049082127
SN - 1472-779X
SP - 1071
EP - 1079
JO - Journal of the Chemical Society, Perkin Transactions 2
JF - Journal of the Chemical Society, Perkin Transactions 2
IS - 7
ER -