Organocatalytic Synthesis of Chiral 1,4-Dihydropyridines with Potential Biological Properties

The 1,4-dihydropyridine core is a widely studied privileged scaffold. Molecules containing this structure are well known calcium channel blockers and are being used already as drugs in the treatment of heart disease. Moreover, recent advances have demonstrated their potential to act against many other diseases. The recent research concerning their activity as multidrug-resistance reversing agents should be highlighted. In the chemistry field, they are soft reducing agents and their chiral analogues have been used in asymmetric reductions with good results.

As shown before, these molecules contain a chiral center in their C4 position. The control of the selectivity in chemical transformations has been a crucial challenge to organic chemists. Nowadays, is well known that the living matter can actually discern between stereoisomers of the same compound. Nevertheless, there are scarce examples of procedures leading to enantiomerically enriched 1,4-DHPs, being most of them based on the use of chiral auxiliaries or chiral resolutions. Finding new and more environmental-friendly processes is also an interesting matter in chemistry, organocatalytic procedures are a perfect tool to achieve this goal.

Herein, we report our recent advances in the development of new organocatalytic methodologies to produce enantiomerically enriched 1,4-DHPs. Interestingly, one of them, brings out another privileged scaffold, such as the oxindole motif. Our methodologies could be perfect keystones leading to further research on the biological properties of these promising compounds.