Recent Advances in Asymmetric Synthesis of 1,4-Dihydropyridines.

The 1,4-dihydropyridine (1,4-DHP) scaffold is a privileged scaffold in numerous therapeutic agents, including L-type calcium channel blockers, mineralocorticoid receptor antagonists, and calcitonin gene-related peptide receptor antagonists. The chirality at the C4 position of the 1,4-DHP core critically influences its pharmacological activity. Recent advances in asymmetric synthesis, particularly through organocatalysis and transition metal catalysis, have enabled efficient and stereoselective routes to access enantiomerically enriched 1,4-DHP derivatives. However, a comprehensive review summarizing these asymmetric synthetic strategies for this pivotal scaffold is still lacking. This article systematically summarizes recent progress in the asymmetric synthesis of 1,4-DHPs, focusing on catalytic systems involving organocatalysts and transition metal complexes. It further highlights their significant potential in constructing key chiral intermediates for pharmaceutical development, aiming to provide novel perspectives for the research and development of chiral 1,4-DHP-based drugs.