Asymmetric Synthesis of Highly Substituted Azapolycyclic Compounds via 2-Alkenyl Sulfoximines: Potential Scaffolds for Peptide Mimetics

The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for
the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to α- or β-amino aldehydes, followed by a
Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free
target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted
heterocycles. In addition to this methodological work, initial results on the biological activity of selected
examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles
in this context is discussed.