Pseudo bases acylation

In a different approach, fluorescence-based DNA microarrays are utilized (88). In a model study, chiral amino acids were used. Mixtures of a racemic amino acid are first subjected to acylation at the amino function with formation of A-Boc protected derivatives. The samples are then covalently attached to amine-functionalized glass slides in a spatially arrayed manner (Fig. 10). In a second step, the uncoupled surface amino functions are acylated exhaustively. The third step involves complete deprotection to afford the free amino function of the amino acid. Finally, in a fourth step, two pseudo-Qn nX. om.Qx c fluorescent probes are attached to the free amino groups on the surface of the array. An appreciable degree of kinetic resolution in the process of amide coupling is a requirement for the success of the ee assay (Horeau s principle). In the present case, the ee values are accessible by measuring the ratio of the relevant fluorescent intensities. About 8000 ee determinations are possible per day, precision amounting to +10% of the actual value ((S(S). Although it was not explicitly demonstrated that this ee assay can be used to evaluate enzymes (e.g., proteases), this should in fact be possible. So far this approach has not been extended to other types of substrates. 

Again, the presence of the non-acylated a-amino group is necessary for the reaction, as demonstrated by the stability of N -chloroacetyl-glutamine (70). The reaction is catalyzed by both acid and base (70) and has been shown to follow pseudo-first-order kinetics between pH 3 and 6 (/). 

Building upon the results obtained by Birman and coworkers. Smith et al. set out to develop an isothiourea-based catalyst that could promote the KR of secondary aryl alkyl alcohols [58]. After screening a range of DHIP catalysts, (2S,3R)-2-phenyl-3-isopropyl-substituted isothiourea (56) proved to be ideal as it afforded high levels of selectivity (s > 17) under low catalyst loadings (<1 mol%) (Scheme 41.12). To explain the enantiodiscrimination, the authors proposed a model where the N-acylated catalyst adopts a conformation that places the phenyl substituent in a pseudo-axial position to minimize 1,2-strain, resulting in a preferential attack of the (R)-enantiomer of the alcohol due to favorable n-n and/or cation-Jt interactions of the TT-system of the alcohol with the acylated isothiouronium catalyst intermediate. 

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