Fluorescence-based screening of asymmetric acylation catalysts through parallel enantiomer analysis. Identification of a catalyst for tertiary alcohol resolution
Er. Jarvo et al., Fluorescence-based screening of asymmetric acylation catalysts through parallel enantiomer analysis. Identification of a catalyst for tertiary alcohol resolution, J ORG CHEM, 66(16), 2001, pp. 5522-5527
A technique for high-throughput screening of kinetic resolution catalysts i
s reported. The method relies on carrying simultaneous kinetic resolutions
in a multiwell plate format wherein each well contains a unique catalyst an
d a small amount of a pH-activated fluorescent sensor (3). By conducting ex
periments 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 enanti
omer but modestly active for another are then reevaluated in conventional k
inetic resolutions. From these screens, a highly selective (k(rel) = 46) pe
ntapeptide (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 tert
iary class.