(3S)-3-hydroxyquinidine, the major biotransformation product of quinidine. Synthesis and conformational studies. X-Ray molecular structure of (3S)-3-hydroxyquinidine methanesuiphonate

Abstract

(3S)-3-Hydroxyquinidine, the major metabolite of the Cinchona alkaloid quinidine, was prepared by synthetic chemical modification or microbial oxidation of quinidine. The structure of this metabolite has been demonstrated to be (3S)-3-hydroxyquinidine by ¹H and ¹³C NMR, IR, UV and mass spectral analysis. Previously published comparisons of the ¹³C NMR spectra of 3-hydroxyquinidine and model compounds were used to establish the absolute stereochemistry of the metabolite (see ref. 8). This assignment has been verified by single-crystal X-ray analysis of (3S)-3-hydroxyquinidine methanesulphonate. The gas- and solution-phase conformational preference of the metabolite derived from molecular modelling and NOE studies are compared with the conformation observed by X-ray crystallography.