Efficient Enzymatic Synthesis of Carbamates in Water Using Promiscuous Esterases/Acyltransferases.

Biocatalysis provides an attractive approach to facilitate synthetic reactions in aqueous media. Motivated by the discovery of promiscuous aminolysis activity of esterases, we exploited the esterase from Pyrobaculum calidifontis VA1 (PestE) for the synthesis of carbamates from different aliphatic, aromatic, and arylaliphatic amines and a set of carbonates such as dimethyl-, dibenzyl-, or diallyl carbonate. Thus, aniline and benzylamine derivatives, aliphatic and even secondary amines could be efficiently converted into the corresponding benzyloxycarbonyl (Cbz)- or allyloxycarbonyl (Alloc)-protected products in bulk water, with (isolated) yields of up to 99 %.

Excelzyme: A Swiss University-Industry Collaboration for Accelerated Biocatalyst Development.

Excelzyme, an enzyme engineering platform located at the Zurich University of Applied Sciences, is dedicated to accelerating the development of tailored biocatalysts for large-scale industrial applications. Leveraging automation and advanced computational techniques, including machine learning, efficient biocatalysts can be generated in short timeframes. Toward this goal, Excelzyme systematically selects suitable protein scaffolds as the foundation for constructing complex enzyme libraries, thereby enhancing sequence and structural biocatalyst diversity.

Effective engineering of a ketoreductase for the biocatalytic synthesis of an ipatasertib precursor.

Semi-rational enzyme engineering is a powerful method to develop industrial biocatalysts. Profiting from advances in molecular biology and bioinformatics, semi-rational approaches can effectively accelerate enzyme engineering campaigns. Here, we present the optimization of a ketoreductase from Sporidiobolus salmonicolor for the chemo-enzymatic synthesis of ipatasertib, a potent protein kinase B inhibitor.

Asymmetric Synthesis of -Alkyl Amino Acids through a Biocatalytic Dynamic Kinetic Resolution of PEGylated -Alkyl Amino Esters.

The first examples of a practical procedure for a lipase-catalyzed dynamic kinetic resolution of PEGylated -alkyl amino esters is reported. This method allows for the preparation of a broad range of aromatic and aliphatic enantiomerically enriched -alkyl unnatural amino acids in up to 98% yield and 99% ee. We have found that PEGylated esters have a significant solubility advantage and improved reactivity over traditional hydrophobic lipase substrates, thereby allowing for efficient and scalable dynamic kinetic resolution (DKR) under aqueous conditions.

Stereoselective Synthesis of the IDO Inhibitor Navoximod.

A highly efficient asymmetric synthesis of the IDO inhibitor navoximod, featuring the stereoselective installation of two relative and two absolute stereocenters from an advanced racemic intermediate, is described. The stereocenters were set via a crystallization-induced dynamic resolution along with two selective ketone reductions: one via a biocatalytic ketoreductase transformation and one via substrate-controlled hydride delivery from LiAlH(OBu). Following this strategy, navoximod was synthesized in 10 steps from 2-fluorobenzaldehyde and isolated in 23% overall yield with 99.