Synthese von Stickstoffmonoxid-modulierenden L-Arginin-Derivaten und Prodrugs für Hydroxyguanidine

Considering the versatile functions of nitric oxide (NO), it is not surprising that dysregulation of endogenous NO-levels contributes to the pathogenesis of various diseases. Within this work different concepts were pursued in order to modulate the NO-generating system. One common synthetic scheme was developed to afford optically pure Nδ-methylated L-arginine besides Nω-hydroxy-Nδ-methyl-L-arginine (NHAM), Nδ-methyl-L-citrulline und Nδ-cyano-Nδ-methyl-L-ornithine as possible metabolites of NO-synthase catalysis. Furthermore, a series of Nω-substituted L-arginines and simple guanidines were synthesized to gain new insights in structure-activity relationships of the dimethylarginine dimethylaminohydrolase (DDAH). Additionally, a number of different prodrugs of Nω-hydroxy-L-arginine were synthesized as potential NO-donors or arginase-inhibitors, respectively. In this context a novel bioactivation concept was investigated: The peptidylglycine α-amidating monooxygenase.

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