6,5-bizyklische Lactame zur Darstellung von metallbindenden Hydroxypyridinonen sowie von dipeptidischen Übergangszustandsanaloga

Mimicking the transition states of enzymes plays an important role in medicinal chemistry. I have developed a synthesis of a potential transition state mimic, starting from a bicyclic oxazolidine lactam. The dipeptide building block, which itself has an intact peptide backbone with one C-O-double bond substituted by an C-O sigma bond in order to mimic the transition state found in proteases, was subsequently incorporated into peptide fragments in order to investigate their inhibitory potential. Bicyclic oxa- or thiazolidine lactams can further serve as precursors for Hydroxypyridinons (HOPOs). The HOPO moiety is the chelating structural feature in several ligand systems already used in a broad range of applications and is therefore an interesting synthetic target. Due to the large number of functional groups present, our synthetic route offers an easy entry for further modifications of the HOPO scaffold. I have developed the synthesis of a variety of hydroxypyridinons with different substitution patterns and investigated their metal affinities, for iron for example a 3:1 complex was observed by UV/vis titration. The reduction of the HOPO moiety to the corresponding piperidin¬ons proceeds diastereoselectively.