STEREOSPECIFIC EPIMERIZATION, OXIDATION AND TOXINE REARRANGEMENT IN CINCHONA ALKALOIDS CATALYZED BY ACETIC ACID

Article abstract of DOI:10.1016/S0040-4020(01)90029-8

Glacial acetic acid catalyzed a novel stereospecific epimerization of chichona alkaloids at C-9.In the presence of water, acetic acid also catalyzed the known toxine rearrangement and oxidation to the corresponding 9-keto derivatives.Addition of acetic anhydride to acetic acid diminished oxidation and epimerization at C-9, and the main products were the results of hydramine fission.Only propionic acid but no other acids, effected similar but not identical transformations.Addition of small quantities of H2O2 or exclusion of oxygen produced quantitative oxidation and rearrangement products, respectively.The catalysis by aqueous solution of acetic acid, involves C-9-OH in the formation of a three-membered ring intermediate.On the other hand, with anhydrous acetic acid, the acetoxyl at C-9 participates in construction of a five-membered ring intermediate.In both cases the reaction appears to be intramolecular.Support for the proposed mechanisms was provided by the isolation of a quarternary salt derived from quinidine, the structure of which was also characterized by X-ray diffraction analysis.Aqueous acetic acid catalyzed the rearrangement of this salt to its corresponding toxine only, and neither oxidation nor epimerization could be observed under conditions employed for the natural alkaloids.