Enzymatic reductive amination

From the very successful developments of the alcohol dehydrogenase technology for production of secondary alcohols and enzymatic reductive amination of keto-acids for production of amino acids, it is expected that we will also soon see applications for other enzymatic redox chemistries for example, reduction of unsaturated carbonyl compounds with... 

Scheme 6.12 Synthesis of (S)-tert-leucine by enzymatic reductive amination.

In a third-generation process, heat-dried methanol-grown P. pastoris expressing endogenous FDH and recombinant Thermoactinomyces PheDH were used to produce 15 kg (S)-allysine ethylene acetal with a yield of 97% mol/mol and> 98% e.e. Both 5-(l,3-dioxolan-2-yl)-2-oxopentanoic acid and lithium-6,6-dimethoxy-2-oxohexanoate served as substrates for the enzymatic reductive amination. 

Figure 3 Preparation of chiral synthon for vasopeptidase inhibitor enzymatic reductive amination of ketoacid acetal (5) to amino acid acetal (4).

ENANTIOSELECTIVE ENZYMATIC REDUCTIVE AMINATION OF 2-(3-HYDROXY-1-ADAMANTYL)-2-OXOETHANOIC ACID... 

Figure 18.1. Enzymatic reductive amination of 2-(3-hydroxy-l-adamantyl)-2-oxoethanoic acid 3 to prepare (S)-7V-BOC-3-hydroxyadamantylglycine 2.

Figure 15.3-1. Schematic of enzymatic reductive amination with cofactor regeneration.

The preparation of 2 by enzymatic reductive amination provides the single enantiomer of the amino acid acetal by a shorter route than the previously published eight-step synthesis of racemic ally sine ethylene acetal. " Unlike the previously described route, the enzymatic route does not reqnire addition and removal of protecting groups, and therefore gives better atom economy. The synthesis of keto acid 1 and enzymatic reductive amination to 2 as described proved to be suitable for the preparation of the large qnantities of the vasopeptidase inhibitor needed for clinical trials. 

FIGURE 16.3 (A) Antidiabetic drug Saxagliptin 5. (B) Enzymatic reductive amination of... 

---