Oxidation of diazenyl-protected N-heterocycles - a new entry to functionalized lactams

Functionalized lactams are an important class of heterocycles since they are useful intermediates in organic synthesis and show biological activity in diverse therapeutic applications. In the herein presented study, a strategy for the synthesis of N-aryldiazenyllactams, offering the direct access to protected lactam derivatives is described. After the formation of triazenes from diazonium salts and commercially available N-heterocycles, oxidation (directed CH activation) with periodate under ruthenium catalysis furnished N-diazenyllactams in one step. To demonstrate the suitability of the resulting lactams for further functionalizations, the alkylation of a N-diazenyllactam is presented for one example.Peer reviewe

Stereodivergent Synthesis of 5-Aminopipecolic Acids and Application in the Preparation of a Cyclic RGD Peptidomimetic as a nanomolar αVβ3 Integrin Ligand

A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained \u3b1- and \u3b4-amino acids. The cis isomer was used as a \u3b4-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for the binding to the isolated \u3b1V\u3b23 integrin was measured (IC50 = 4.2 \ub1 0.9 nM). A complete 1H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with Cilengitide