Synthesis and structural study of semicarbazone-containing 1,4-dihydropyridine

A new series of 1,4-dihydropyridines (1,4-DHPs) bearing a semicarbazone moiety on C5 (8a-g) have been synthesized from suitably functionalized 1,4-DHPs (2) and semicarbazide. Compounds (8a-g) did not cyclize to the respective seven member ring though this is a favoured 7-endo-trig process. Geometrical and structural features determined by theoretical, DFT (B3LYP/6-31G*) and experimental (X-Ray diffraction) data, reveal the presence of a low energy stereoisomer, namely (E) s-trans, which is also present in solution according to NOe experiments carried out on compound (8a). These geometrical findings account for the lack of cyclization of compounds (8a-g), and reveal that they meet the structural requirements needed for biological activity as calcium-channel modulators.