The reactions of 3-substituted 2-oxindoles with nitrosobenzene give two products with different biological activities. Aminoxylation products are found in many natural products with a wide range of biological activity, and also in pharmaceuticals such as SM-130686 and TMC-95A. Hydroxyamination products are involved in the structures of potential drug candidates (NITD609, SSR-149415, and AG-041R) for the treatment of malaria and stress related diseases. The catalytic reaction has been extensively studied in the presence of cinchona alkaloid derivatives. Experiments show that the selection of the catalyst has a significant effect on the product distribution. For example, the reaction of a 3-substituted oxindole with nitrosobenzene gives hydroxyamination products with the C6`-hydroxy derivative of quinine, while aminoxylation products were obtained in the presence of C6`-dimer of quinidine. This lecture will describe how different cinchona alkaloids steer the product distribution in preference of one of the products using a novel computational approach combining drug design tools with high level quantum mechanical calculations.

How cinchona alkaloids steer the product distribution in the reactions of oxindoles with nitrosobenzene

253rd National Meeting (2017)

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