Controlling thiiranium intermediates-a new route to an iNOS inhibitor

Our synthetic efforts towards an iNOS (inducible isoform of the nitric oxide synthase) inhibitor led us to the relatively unexplored field of generating and controlling the reactivity of chiral, unsymmetrical thiiranium species. We found that product regiochemistry depends on a tunable equilibrium, the understanding of which proved pivotal in defining a new route to a drug substance. The development of a new amidination method is also discussed.

Graphical abstractAn equilibrium between A and C exists presumably via thiiranium ion B. The dynamics of this equilibrium are dominated by the leaving group ability/nucleophilicity of X and this is exploited in defining a new route to an iNOS (inducible isoform of nitric oxide synthase) inhibitor. A new amidination method is also described.Download full-size image