Where does amlodipine come from?

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

^References

1. Brody F, Ruby PR. Synthetic and Natural Sources of the Pyridine Ring. Chemistry of Heterocyclic Compounds: John Wiley & Sons, Inc.; 2008:99-589.
2. R. Murugan EFVS. Pyridines: from lab to production. Great Britain: Elsevier Ltd.; 2013.
3. PubChem Compound DataBase. U.S. National Library of Medicine NIH. https://pubchem.ncbi.nlm.nih.gov/compound/1049 Accessed May 4, 2017.
4. 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.
5. 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.
6. 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.
7. Haji M. Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates. Beilstein journal of organic chemistry. 2016;12(1):1269-1301.