Dihydropyridines like amlodipine, are derived from the heterocyclic aromatic compound pyridine.1 Small amounts of naturally occurring pyridine can be found in plant enzymes, alkaloids, and shale.1 Industrial production of pyridine can be achieved by extraction from crude coal tar.2 Synthetic pyridine can be synthesized by reacting acetaldehyde, formaldehyde and ammonia under high temperature-vapor conditions.3,4
The majority of pyridine used today is synthesized by means of multicomponent reactions (MCRs).5-7 A variety of reagents can be employed for pyridine synthesis.5-7 For example, one multicomponent reaction includes the condensation of aldehyde, malononitrile, and thiol.5 Once derived, it can be synthesized into different classes of antihypertensive agents.5,6
- Brody F, Ruby PR. Synthetic and Natural Sources of the Pyridine Ring. Chemistry of Heterocyclic Compounds: John Wiley & Sons, Inc.; 2008:99-589.
- R. Murugan EFVS. Pyridines: from lab to production. Great Britain: Elsevier Ltd.; 2013.
- PubChem Compound DataBase. U.S. National Library of Medicine NIH. https://pubchem.ncbi.nlm.nih.gov/compound/1049 Accessed May 4, 2017.
- Tognotti L, Petarca L, D'Alessio A, Benedetti E. Low temperature air oxidation of coal and its pyridine extraction products. Fuel. 1991/09/01 1991;70(9):1059-1064.
- Evdokimov NM, Magedov IV, Kireev AS, Kornienko A. One-Step, Three-Component Synthesis of Pyridines and 1,4-Dihydropyridines with Manifold Medicinal Utility. Organic Letters. 2006/03/01 2006;8(5):899-902.
- Hyster TK, Rovis T. Pyridine synthesis from oximes and alkynes via rhodium (iii) catalysis: Cp* and Cp t provide complementary selectivity. Chemical Communications. 2011;47(43):11846-11848.
- Haji M. Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates. Beilstein journal of organic chemistry. 2016;12(1):1269-1301.