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Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Fluorescence-based screening of asymmetric acylation catalysts through parallel enantiomer analysis. Identification
E R Jarvo1, C A Evans, G T Copeland
1Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467-3860, USA.
Abstract:
A technique for high-throughput screening of kinetic resolution catalysts is reported. The method relies on carrying simultaneous kinetic resolutions in a multiwell plate format wherein each well contains a unique catalyst and a small amount of a pH-activated fluorescent sensor (3). By conducting experiments such that each catalyst is evaluated in parallel in the presence of each isolated enantiomer, an indication of catalyst activity is obtained on a per enantiomer basis. Catalysts that are highly active for one enantiomer but modestly active for another are then reevaluated in conventional kinetic resolutions. From these screens, a highly selective (k(rel) = 46) pentapeptide (4) was obtained for a model secondary alcohol (1). In addition, peptide 10 was found to afford excellent selectivities (k(rel) > 20) for a number of alcohol substrates (9a-9f) in the traditionally challenging tertiary class.
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