A. Asymmetrische Organokatalyse mit kleinen Peptiden und neuen bifunktionellen organischen Verbindungen. B. Ansätze zur asymmetrischen Produktkatalyse und zur Synthese der Naturstoffhybride

Abstract

The structure/activity relationship for some (S)-histidine-based dipeptide catalysts in direct aldol reactions have been examined. The reactivities and stereoselectivities are shown to be dependent upon the intramolecular cooperation of side-chain functional groups and the presence of a suitable combination and sequence of amino acids. Good yield (up to 96%) and enantioselectivities (up to 76% ee) were obtained with electron-deficient aromatic aldehydes in the presence of H-Leu-His-OH. The influence of different chiral and achiral co-catalysts on the reaction rates, yield and enantioselectivities has also been evaluated. Significant increases in the acceleration of the reaction, most remarkable for achiral trans-2,5-dimethylpiperazine as co-catalyst and the improved yields, were demonstrated. A new and effective organocatalytic system: primary amine derived chiral thiourea catalyst and AcOH-H2O additive, which converts different ketones to ?-nitrostyren in high yields (82-99%) and enantioselectivities (90-99%) has been described. The transition state geometries for formation of R and S enantiomers in this Michael addition have been calculated and analyzed. When product and catalyst are the same: The chiral product of asymmetric Mannich and Aldol reaction investigated under various experimental conditions and by calculation, is shown to act as a chiral catalyst for its own formation (autocatalysis). A generally applicable catalytic cycle is proposed to involve equilibria between hydrogen-bonded substrate-product complexes. A well-known active substance, which is already used against malaria, and shows also in addition cytotoxic activity in cancer cells, is Artesunat (semisynthetic derivative of the Artemisinins). One of six manufactured hybrid natural substances, which contains Artesunat, proved as very active against the malarial parasite.