Today, there is a high demand for enantiopure building blocks in chemistry and pharmaceutical industry. In addition to enzymatic approaches, mainly trial and error processes have discovered various enantioselective catalysts in the last decade. In 2008 Schreiner et al. introduced a highly enantioselective tetrapeptide for the acylative kinetic resolution (KR) of rac-cycloalkane-1,2-diols.This thesis tries to shed some light on the factors that are responsible for the excellent selectivity of Boc-L-(pi-Me)-His-AGly-L-Cha-L-Phe-OMe in the kinetic resolution (KR) of rac-cycloalkane-1,2-diols and therefore may lead to a more rational catalyst design in future studies. For that reason, all components (substrate, electrophile and catalyst) of the reaction were individually varied and the influence on the selectivity detected, as well as compared to the model system. Boc-L-(pi-Me)-His-AGly-L-Cha-L-Phe-OMe was tested in KR utilizing different electrophiles (e.g. Boc2O, AcCl, diphenylchlorophosphate, diethylchlorophosphate and various benzenesulfonylchlorides) to investigate the influence of the electrophile on the selectivity. It was found that the selectivity depends on the counterion of the electrophile as well as on the electrophile itself. For Ac2O and Boc2O, good values for the enantiomeric excess (ee) could be observed, while for sulfonylation-, phosphorylation and acetylation reactions (utilizing AcCl) the transfer of the electrophile was possible, but rather unselective.The influence of hydrogen bonding interactions on the selectivity was also tested by using trans-1,2-diaminocyclohexane, trans-2-aminocyclohexanol, trans-cyclohexane-1,2-dithiol and trans-2-mercaptocyclohexanol as substrates in the KR. Strong hydrogen bonding interactions seem to be responsible for the selectivity, because for the structural related amino alcohol, diamine, dithiol and mercoptoalcohol, some activity, but only low (diamine, aminoalcohol) or no selectivity (dithiol, mercaptoalcohol) could be observed. In order to identify the influence of the spacer, the structure determining adamantane amino acid (AGly) was modified. For that reason AGly was elongated at the C- and N-terminus, incorporated into the model peptide and utilized in the KR of trans-cyclohexane-1,2-diol, trans-cyclohexane-1,3-diol, 1-phenylethanol and BINOL. For our test reaction (KR of trans-cyclohexane-1,2-diol ) the ee decreased dramatically, if flexible spacer were used. The conformation of Boc-L-(pi-Me)-His-AGly-L-Cha-L-Phe-OMe (e.g., beta-turn) in solution was investigated by NMR- and IR-spectroscopy, as well as by computational methods. No evidences for a permanent secondary structure were found, therefore the chiral environment is probably generated by a dynamic binding event induced fit of the substrate and the catalyst.In a second project we envisioned the modification of the catalytically active Boc-pi-methyl histidine amino acid. Methylation of the tau-position of the methylimidazole moiety yielded in N,N -dimethyl histidinium iodide, which can be in-situ transformed into a free NHC by base and offers an easy access to new asymmetric reactions (e.g., benzoin condensations and oxidative esterification). The synthesis of two different peptides bearing a dimethylimidazolium- or methylthiazolium-salt-group is described. The peptides were tested in benzoin condensations, but in contrast to dimethylimidazolium iodide (symmetric test catalyst), only low product yields were observed. Unfortunately, the catalytically active carbene moiety of the catalyst seems to attacks its on backbone and decomposes under the reaction conditions utilized for the benzoin condensation. Hence, shorter peptides should be investigated.
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