The Berkowitz group has been examining the use of enzymes as analytical tools to faciliate the development and optimization of new catalytic combinations for transformations of synthetic interest (In Situ Enzymatic Screening ISES). The advantage of this approach is that for reactions for which the method is well–suited, the experimentalist observes real time enzymatic readout on an organic reaction of interest, without the need to quench the organic reaction or to draw aliquots. In the case at hand, we are screening for transition metal–ligand combinations that promote an intramolecular allylic amination entry into “quaternary” α–vinyl amino acids, potential mechanism–based inactivators (MBIs) for vitamin B<sub>6</sub>–dependent enzymes. Each successful formation or turnover of a π–allyl metal complex in the organic layer releases a water–diffusible leaving group. A reporting enzyme in an adjoining aqueous layer enzymically processes the leaving group, giving rise to a spectroscopic signal associated with the enzymatic chromophore. This enzyme–based screen obviates the need to install a chromophore in the substrate, leaving group or product and allows for parallel screening of an array of catalytic combinations (e.g. varying the metal, ligand and nitrogen protecting group). Our progress toward developing an asymmetric version of this chemistry will be described.

Exploiting enzymes from (hyper)thermophiles for <i>in situ</i> enzymatic screening (ISES) at elevated temperature: Toward a catalytic, asymmetric entry into quaternary, α–vinyl amino acids

2019 Fall National Meeting

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Exploiting enzymes from (hyper)thermophiles for in situ enzymatic screening (ISES) at elevated temperature: Toward a catalytic, asymmetric entry into quaternary, α–vinyl amino acids