The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of a Ritter reaction with a Wagner−Meerwein rearrangement from noradamantane alcohols is reported. Several of the novel amines displayed low micromolar activities against several H1N1 influenza virus strains, including the amantadine-resistant A/PuertoRico/8/34 strain. Most of the compounds did not show cytotoxicity for MDCK cells.

The first total syntheses of the proposed structures of kopeolin (1) and kopeolone (3) have been achieved from a common enantiopure chiral building block obtained by a chemoenzymatic enantioconvergent methodology. The syntheses feature two key steps: a one-pot reduction/diastereoselective protonation followed by a highly diastereoselective addition of an organocerate. The synthetic structures were fully characterized and all stereocenters were confirmed. The results show that the two previously reported structures were not assigned correctly, and suggest an initial structural misassignment during the isolation of the natural products. Thus, two revised structures, 1' for kopeolin and 3' for kopeolone, are proposed.

An enantioselective total synthesis of two sesquiterpenoids, kopeolin and kopeolone, has been achieved. Using the diastereoselective addition of an organocerate as a key step, we controlled the absolute stereochemistry of a crucial stereocenter present in these natural products. This approach allowed us to confirm a structural revision that we previously proposed (Chem.-Eur. J. 2013, 19, 10632-10642) and to fully characterize these natural products while elucidating their absolute stereochemistry.

Revised Structure, Total Synthesis, and Absolute Configuration of Kopeolin (I) and Kopeolone (II). -(MIQUET, S.; BREMOND, P.; AYELA, B.; MARQUE, S. R. A.; AUDRAN*, G.; J. Org. Chem. 79 (2014) 5, 2268-2273, http://dx.doi.org/10.1021/jo402572b ; CNRS, Aix Marseille Univ., F-13397 Marseille, Fr.; Eng.) -Roessler 33-205