Differentiation of Cinchonine and Cinchonidine Derivatives Through 13C NMR Analysis of the Quinuclidine Ring

Abstract

With a view to developing a procedure for the differentiation of cinchonine derivatives from cinchonidine derivatives by NMR analysis, experimental data on cinchonine and cinchonidine, after their dissolution in different solvents (CDCl₃, CD₃OD and DMSO-d₆), were compared with theoretical data, originating from different methodologies: DP4, DP4+ , J-DP4 and ANN. Taking into account the lower computational consumption, as well as the greater efficiency in differentiation, the method selected was the trained artificial neural networks (ANN), which considered only the ¹³C data from the quinuclidine ring. The method successfully differentiated derivatives originating from OH group protection in ester and ether forms; replacement of the OH group by F and NH₂; insertions of N₃, 1H-1,2,3-triazol-1-yl and CH₃O groups, linked to the quinoline ring; conversion of the vinyl group to the 1-benzyl-1H-1,2,3-triazol-4-yl; and of hydrogenation, dehydrogenation, and bromination of the vinyl group. In all cases the application of the ANN method succeeded in differentiation of cinchonine from cinchonidine derivatives.