Correlation of the crystal structures of diastereomeric artemisinin derivatives with their proton NMR spectra in CDCl3

Abstract

Large differences were observed in the 1 H NMR chemical shift pattern of the protons adjacent to the ether linkages of two diastereomeric artemisinin derivatives. These differences can be explained by the shielding/deshielding effects of the nitrophenyl group on these protons. The crystal structures of these diastereomers (one as the ethyl ester and the other as the acid analog) showed that the nitrophenyl group is positioned on opposite sides of the fused ring system in the two diastereomers. The upfield or downfield 1 H NMR signal of the protons adjacent to the ether linkages [H(10) and H(12)] of the individual diastereomers correlates with whether the phenyl ring sits under or beside the proton. The crystal structure of the acid analog contains an infrequently observed intermolecular hydrogen bond between the carboxylic acid proton and an ether O atom [O(11)]. However, since the NMR spectra in solution are consistent with the crystal structures, packing forces do not appear to be responsible for the orientation of the nitrophenyl group.