A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza. The two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.

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Diastereoselective Synthesis of Highly Substituted Polycyclic Scaffolds via a One--Pot Four-Step Tandem Catalytic Process. -A one-pot four-step multi-reaction process involving a thermal Overman rearrangement, a tandem metathesis reaction, and a Diels-Alder reaction is developed for the diastereoselective synthesis of aminobicyclononanes and -decanes with up to five stereogenic centers. -(GRAFTON, M. W.; JOHNSON, S. A.; FARRUGIA, L. J.; SUTHERLAND*, A.; Tetrahedron 70 (2014) 40, 7133-7141, http://dx.