1H and 13C NMR studies on the conformation of N-methyl diastereomers of (+)-glaucine hydrotrifluoroacetate, an aporphine alkaloid salt

Abstract

A 3 : 1 ratio of N-methyl diastereomers of (+)-glaucine hydrotrifluoroacetate was observed at slow exchange by 1H NMR spectroscopy (300 MHz, CD2Cl2), but the spectrum was too complex to be interpreted solely by one-dimensional methods. However, the E.COSY 2D NMR spectrum afforded all proton chemical shift and coupling constant data for both N-methyl diastereomers. Surprisingly, there are few or no cases where the E.COSY data have been analysed manually and have thereby effected a full assignment of the 1H NMR spectrum of a molecule. While X-ray crystallographically determined structures of aporphine alkaloids have B-rings with either M- or P-conformations [as denoted by the sign of the C(3a)–C(4)–C(5)–N torsion angle], measured vicinal coupling constants together with difference-NOE experiments showed both solution-state species of (+)-glaucine to have the M-conformation for the B-ring. The major and minor solution-state species differ by configuration at nitrogen: the 6S,6aS-major species has an equatorial N-methyl group, and the 6R,6aS-minor species has an axial one. The major contributor to the fast exchange limit structure of glaucine free base has an equatorial N-methyl group.