METAL CARBONYL MEDIATED REACTIONS - APPLICATIONS IN THE SYNTHESIS OF POTENTIAL GALECTIN INHIBITORS
Doctoral thesis, 2008
This work reports the development of an asymmetric version of the Nicholas reaction using monodentate phosphoramidites as ligands, which enables asymmetric synthesis from racemic starting material. In addition, we describe the application of metal carbonyl mediated reactions, such as the Pauson-Khand reaction (PKR) and reactions involving cationic iron carbonyl dienyl complexes, for the synthesis of potential galectin inhibitors, implicated in human inflammatory responses and various pathologies.
Papers I and II describe the development of an asymmetric version of the Nicholas reaction using chiral phosphoramidite ligands. (S)-BINOL was used as the chiral component and 14 different amines were evaluated in the synthesis of the phosphoramidite ligands. After a selection among the best ligands in terms of enantioselectivity, the scope of the reaction was expanded to several substrates and a wider variety of nucleophiles. We have shown the first successful example of an asymmetric Nicholas reaction, using chiral ligands, with promising results.
Papers III and IV demonstrate how organometallic chemistry can be applied towards the synthesis of potential galectin inhibitors. The Pauson-Khand reaction allowed the introduction of cyclopentenones with different substituents at the C3 position of D-galactose. In addition, we have shown that iron carbonyl chemistry is a good method for the introduction of a diene or an aromatic group on a galactose scaffold. All these approaches enable the synthesis of new galactose derivatives which will facilitate studies of galectins and their roles in cancer and proinflammatory diseases.