Development of Immobilized Carreira (Phosphoramidite, Olefin) Ligands and Application in Iridium-Catalyzed Asymmetric Allylic Amination.

A family of polystyrene-supported (phosphoramidite, olefin) ligands -, based on the original design by Defieber and Carreira, has been developed and applied in iridium-catalyzed asymmetric allylic amination of unmasked allylic alcohols (27 examples, up to 99% ee). Among them, functional resins and exhibit important advantages such as easy preparation, ligand recyclability, and easy handling for sequential use. As a distinctive advantage, the catalytic use of the iridium complexes of and allows the straightforward reuse of a high percentage of the expensive iridium metal involved in the complexes, which is not achievable under homogeneous conditions with the corresponding monomeric complexes.

An enantio- and diastereoselective approach to indoloquinolizidines in continuous flow.

Merging polymer-supported asymmetric organocatalysis with continuous flow in a packed bed reactor has been used as the key, enantiodetermining step in a short synthesis of indoloquinolizidines. Using this approach, a highly enantioselective, solvent-free and rapid conjugate addition of dimethyl malonate to a diverse family of cinnamaldehydes in continuous flow, allowing the preparation of relevant oxodiesters in multigram amounts has been developed. The obtained Michael adducts have been used to complete an expedient diastereoselective synthesis of indoloquinolizidine cascade Pictet-Splengler cyclisation-lactamisation in continuous flow.

Small Molecule-Peptide Conjugates as Dimerization Inhibitors of Trypanothione Disulfide Reductase.

Trypanothione disulfide reductase (TryR) is an essential homodimeric enzyme of trypanosomatid parasites that has been validated as a drug target to fight human infections. Using peptides and peptidomimetics, we previously obtained proof of concept that disrupting protein-protein interactions at the dimer interface of TryR TryR offered an innovative and so far unexploited opportunity for the development of novel antileishmanial agents. Now, we show that linking our previous peptide prototype to selected hydrophobic moieties provides a novel series of small-molecule-peptide conjugates that behave as good inhibitors of both TryR activity and dimerization.