Step 3: Formation of the dihydropyridine

Dihydropyridine synthesis - Organic chemistry

Hantzsch Dihydropyridine Synthesis

Chiral to achiral transformations: the substrate undergoes metabolism at the center of chirality, resulting in a loss of asymmetry. Examples include the aromatization of the dihydropyridine calcium channel blocking agents, e.g., Nilvadipine, to yield the corresponding pyridine derivative and the oxidation of the benzimidazole proton pump inhibitors, e.g., Omperazole, which undergoes CYP 3A4–mediated oxidation at the chiral sulphoxide to yield the corresponding sulphone. In the case of omeprazole, the reaction shows tenfold selectivity for the S-enantiomer in terms of intrinsic clearance.

The Hantzsch 1,4-dihydropyridine synthesis as a route to bridged pyridine and dihydropyridine crown ethers

Hantzsch Dihydropyridine Synthesis by Kim Couch on Prezi

For example, the epimerization of carbenicillin appears to be so rapid as to preclude the use of a single isomer. Whereas, in the case of latamoxef, a compound with a half-life of epimerization under physiological conditions only slightly shorter than the apparent serum elimination half-life, the single isomer or mixture question is more difficult to answer. In the case of the quinolones, particularly with respect to ofloxacin and its derivatives, there can be little doubt of the significance of stereochemical considerations, particularly in terms of providing an insight into the mechanism of action at a molecular level, potency and selectivity.

In contrast, differences between diastereoisomers may occur as a result of their differential solubility. However, in the case of compounds transported via carrier-mediated mechanisms, e.g., facilitated diffusion or active transport, processes involving a direct interaction between a Substrate and a carrier macromolecule, stereoselectivity is expected. Preferential absorption of the L- compared to the D-enantiomers of dopa and methotrexate have been reported.