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.

The data reported in this paper demonstrate that great care must be taken when choosing an appropriate catalyst for a given metathesis reaction. First-generation catalysts were found to be useful in the metathesis of sterically unhindered substrates. Second-generation catalysts (under optimised conditions) showed good to excellent activities toward sterically hindered and electron-withdrawing group (EWG)-substituted alkenes that do not react using the first-generation complexes. A strong temperature effect was noted on all of the reactions tested. Interestingly, attempts to force a reaction by increasing the catalyst loading were much less effective. Therefore, when possible, it is suggested that metathesis transformations should be carried out with a second-generation catalyst at 70 degrees C in toluene. However, different second-generation catalysts proved to be optimal for different applications and no single catalyst outperformed all others in all cases. Nevertheless, some empirical rules can be deduced from the model experiments, providing preliminary hints for the selection of the optimal catalysts.

Verley type transition state 8 (Scheme 3). The use of acetone cyanohydrin as a cyanide source takes advantage of both the reversibility of cyanohydrin synthesis and the steric influence on the position of the equilibrium, which is generally more favorable for addition to aldehydes than to ketones.Acyl cyanides, 9 cyanoformates, 10 and cyanophosphonates 11 can also be used as cyanating agents and have the major advantage of producing O-protected cyanohydrins which do not revert to carbonyl compounds; thus, the cyanohydrin formation becomes irreversible, and even substrates for which the equilibrium between carbonyl compound and cyanohydrin is unfavorable can be prepared Michael North was born in Blackburn, England, in 1964. He obtained his B.Sc. in 1985 from the University of Durham and his D.Phil. in 1988 from the University of Oxford for work on the synthesis of nonracemic amino acids carried out in the group of Professor Sir J. E. Baldwin. After a two-year postdoctoral position in Professor G. Pattenden's research group at the University of Nottingham, he was appointed to his first academic post at the University of Wales at Bangor. In 1999 he moved to King's College London and was promoted to Professor of synthetic organic chemistry in 2001. In 2004, he moved to his current position as Professor of organic chemistry and joint director of the University Research Centre in Catalysis and Intensified Processing at the University of Newcastle upon Tyne. Professor North has published over 100 original papers and also holds five patents. His research interests are centered on the design and mechanistic study of new catalysts with applications including asymmetric carbon-carbon bond formation, carbon dioxide chemistry, and polymer chemistry. In 2001 he was awarded the Descartes Prize by the European Commission for his work on asymmetric cyanohydrin synthesis using metal(salen) complexes.

DNA-encoded libraries have emerged as a widely used resource for discovery of bioactive small molecules and offer substantial advantages compared to conventional small-molecule libraries. Here we developed and streamlined multiple fundamental aspects of DNA-encoded and DNA-templated library synthesis methodology, including computational identification and experimental validation of a 20×20×20×80 set of orthogonal codons, chemical and computational tools for enhancing the structural diversity and drug-likeness of library members, a highly efficient polymerase-mediated template library assembly strategy, and library isolation and purification methods. We integrated these improved methods to produce a second-generation DNA-templated library of 256,000 small-molecule macrocycles with improved drug-like physical properties. In vitro selection of this library for insulin-degrading enzyme (IDE) affinity resulted in novel IDE inhibitors including one of unusual potency and novel macrocycle stereochemistry (IC50 = 40 nM). Collectively, these developments enable DNA-templated small-molecule libraries to serve as more powerful, accessible, streamlined, and cost-effective tools for bioactive small-molecule discovery.