Biocatalytic Asymmetric Synthesis of (Di)hydroxycarbonyls

The current demand of new ways to perform chemical synthesis in a more sustainable way has brought up many new technologies. One novel approach combines isolated enzymes which are unrelated in nature or even derived from different organisms for the catalysis of a non-natural chemical reaction in an environmentally benign way. These setups are termed biocatalytic cascade reactions and consist of multiple steps, which are all performed in a single reaction vessel. The question aroused, if this technology can be utilized to transform molecules derived from biomass into more complex structures within a novel biocatalytic cascade. Amino acids obtained from renewable resources will be the starting material for the envisioned multistep reaction. In the first step of the sequential route the amino acid is deaminated by a suitable already well characterized enzyme, subsequently undergoing an asymmetric carbon-carbon bond forming reaction mediated by an aldolase. Aldolases are enzymes which can catalyze the bond formation between to carbon atoms in a highly selective fashion. The combination of these enzymes will enable the direct valorization of cheap easily accessible renewable chemicals. The products formed in this reaction are hydroxycarbonyl compounds, serving as useful building blocks which can be easily modified to all kinds of structure motifs classes showing bioactivity.

The switch to enzymes as catalysts of choice is one way to change synthetic technologies towards more sustainability, as chemists are not anymore dependent on expensive and toxic metals, but on proteins which are accessible through simple fermentation processes. However, among the enzymatic catalysts - actually called biocatalysts - are those understudied which are capable to construct the carbon framework of complex organic molecules as needed in natural products, pharmaceuticals, fragrances and many other applications. Hence, the combination of carbon-carbon forming biocatalysts with the more established catalysts, which are known for functional group altering, was investigated and it turned out that they are perfectly compatible and allow the direct access of chemical building blocks challenging to access with conventional methodologies directly outof renewable resources.