High-Yield Biocatalytic Amination Reactions in Organic Synthesis

Abstract

The amino functionality gives important biological activity in pharmaceutical compounds. The formation of chiral amines and amino acids can be accomplished by several chemical routes but enzymatic formation of amines offers many advantages in preparing chiral amino compounds or amination of fragile compounds compared to stoichiometric or catalytic chemical transformations. Biocatalytic routes to amines primarily use enzymes of the transaminase class (also known as aminotransferases) which transfer the amino function from a donor organic compound to a ketone or aldehyde acceptor. Although known since 1937, the transamination reaction experiences renewed interest due to the advances in biochemistry and molecular biology and the excellent selectivity of biocatalysts. Other enzymes that have been used to synthesize chiral amines are from the phenylalanine ammonia lyase class that use ammonia as the amino source. The use of recombinant enzymes for the biocatalytic preparation of amines is expanding at a great rate and the range of enzymes revealed in DNA sequence databases is of the order of tens of thousands. Since a large number of substrates like ketones, hydroxyketones and ketoacids can be made by chemical synthesis, the growing toolbox of -, -, -, -, -and -transaminases enable the synthesis of various new chemical entities by biocatalytic amination reactions. In order to simplify the isolation and purification of the product, it is useful to drive the amination reaction to completion. The biocatalytic processes that have been developed show different strategies of overcoming the kinetic limitations of the transaminase reactions and show how some enzymes have been used in processes to make large quantities of chiral compounds with amino functionalities.

Features and technical applications of ω-transaminases

“…Among them, the w-TA has gained growing attention for the preparation of enantiopure amines because w-TA is the only naturally occurring enzyme capable of stereoselective amination of ketones. Recently, a couple of review papers on w-TAs have been published, dealing with the scope of available w-TAs and their applications to preparation of chiral amines (Ward and Wohlgemuth 2010;Koszelewski et al 2010c;Tufvesson et al 2011;Höhne and Bornscheuer 2009). In this review, following the introductory description of enzyme nomenclature and w-TA history, we provide three sections: biochemical features of w-TAs, quest for new enzymes, and crucial factors to process design for production of chiral amines.…”

First example of an organocatalytic asymmetric Mannich reaction between aldimines of glycinates and sulphonyl imines

“…[27][28][29] The hydroxyl group of the aldimine is vital for the high reactivity and enantioselectivity. 30,31 Moreover, studies show that the hydroxyl group could stabilize ␣ anions in the presence of base (Scheme 1).…”

Biocatalytic Process Design and Reaction Engineering

“…Biocatalytic reaction platforms with numerous biocatalysts and their applications, established over the years for many reaction classes like reductions [40][41] , oxidations [42][43][44] , hydrolysis [45][46] , aminations [47][48] or phosphorylations [49][50] , have paved the way for extending the biocatalyst applications to new substrates and for putting together new synthetic routes. Best practices in the assembly of synthetic biocatalytic as well as chemical synthetic reactions involve rapid prototyping of the most critical reaction steps in order to obtain the first proof-of-principle.…”