Reductive Amination in the Synthesis of Pharmaceuticals
Top Cited Papers
- 21 October 2019
- journal article
- review article
- Published by American Chemical Society (ACS) in Chemical Reviews
- Vol. 119 (23), 11857-11911
- https://doi.org/10.1021/acs.chemrev.9b00383
Abstract
Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among biologically active compounds. It is one of the key approaches to C–N bond construction due to its operational easiness and a wide toolbox of protocols. Recent studies show that at least a quarter of C–N bond-forming reactions in the pharmaceutical industry are performed via reductive amination. This Review concisely compiles information on 71 medical substances that are synthesized by reductive amination. Compounds are grouped according to the principle of action, which includes drugs affecting the central nervous system, drugs affecting the cardiovascular system, anticancer drugs, antibiotics, antiviral and antifungal medicines, drugs affecting the urinary system, drugs affecting the respiratory system, antidiabetic medications, drugs affecting the gastrointestinal tract, and drugs regulating metabolic processes. A general synthetic scheme is provided for each compound, and the description is focused on reductive amination steps. The green chemistry metric of reaction mass efficiency was calculated for all reactions.Keywords
Funding Information
- RFBR (18-33-20065)
- Council of the President of the Russian Federation (MK- 1736.2019.3)
- RUDN 5-100
This publication has 180 references indexed in Scilit:
- Recent Progress in the Chemistry of Mucohalic Acids: Versatile Building Blocks in Organic SynthesisSynlett, 2013
- Efficient Preparation of α-KetoacetalsMolecules, 2012
- A novel asymmetric synthesis of cinacalcet hydrochlorideBeilstein Journal of Organic Chemistry, 2012
- An Improved and Impurity-Free Large-Scale Synthesis of Venlafaxine HydrochlorideOrganic Process Research & Development, 2011
- Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin ManufactureScience, 2010
- A Single Nucleotide Polymorphism within the Acetyl-Coenzyme A Carboxylase Beta Gene Is Associated with Proteinuria in Patients with Type 2 DiabetesPLoS Genetics, 2010
- Characterization of Route Specific Impurities Found in Methamphetamine Synthesized by the Leuckart and Reductive Amination MethodsAnalytical Chemistry, 2009
- Asymmetric Allylboration of Acyl Imines Catalyzed by Chiral DiolsJournal of the American Chemical Society, 2007
- Mild Palladium-Catalyzed Selective Monoarylation of NitrilesJournal of the American Chemical Society, 2005
- The pharmacological effect of citalopram resides in the (S)-(+)-enantiomerJournal of Neural Transmission, 1992