N-inversion-associated conformational dynamics is unusually rapid in morphine alkaloids.
(13)C DNMR studies of codeine and sinomenine (derivatives of N-Me morphinan) indicated that N-inversion-C-N rotation (NIR) is unusually fast for these substituted piperidines when compared with other N-Me piperidines. Since only broadening, but no signal splitting, was reached at low temperatures and the difference of chemical shifts (Delta delta) for individual conformers with the equatorially and axially oriented N-Me substituent was unavailable, the limits of the NIR barrier for these amines were determined by line shape analysis using Delta delta values provided by ab initio calculations. On the basis of the comparison of experimentally determined (13)C NMR chemical shifts for tropane conformers with the ones calculated at different theory levels for this N-Me piperidine, the B3LYP/6-31G(p)/GIAO level was chosen as a sufficiently accurate method for calculations of Delta delta. By this new "semiempirical" procedure of line shape analysis the NIR barrier for the studied morphinans lies within a 25-27 kJ mol(-1) (6.0-6.5 kcal mol(-1)) range. A low NIR barrier for morphine alkaloids is supposed to be an important factor in the activation of morphine receptor.
Belostotskii
Anatoly M
AM
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel. belostot@mail.biu.ac.il
Goren
Zafrir
Z
Gottlieb
Hugo E
HE
D000470:Alkaloids / Q000737:chemistry*; D003061:Codeine / Q000737:chemistry; D018360:Crystallography, X-Ray; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D009010:Monte Carlo Method; D009019:Morphinans / Q000737:chemistry; D009020:Morphine / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000470:Alkaloids; D009019:Morphinans; C009271:sinomenine; D009020:Morphine; D003061:Codeine