The main topics of our research group are:

The chemistry of α-aminonitriles

Natural product research and structure elucidation

Synthesis of glycosylated templates as potential saccharide mimetics

Synthesis of natural products

α-Aminonitriles as building blocks in organic chemistry
Although the chemistry of α-aminonitriles is known for over 160 years, these compounds are still relevant for today’s synthetic chemists. Due to their different modes of reactivity, α-aminonitriles can be employed as building blocks in the synthesis of a large variety of heterocyclic compounds, alkaloids, α-amino acids and branched amines.

In our research group, we are developing new strategies for the synthesis of amines and N-heterocycles and their application for the preparation of natural products. These methods make use of deprotonated α-aminonitriles as acyl anions or stabilized α-aminocarbanions and e.g. permit the preparation of mono- and dimeric benzylisoquinoline alkaloids with high optical purity.

Natural product research and structure elucidation

Crop protection becomes increasingly important as the world’s population grows while arable land is being lost due to erosion and the changing climate. The challenges of current agrochemical research lie not only in the fulfillment of stricter regulatory requirements but also in the competition with the pathogens’ augmenting resistance. These means greatly motivate interdisciplinary research aimed at identifying new lead structures for potent and environmentally compliant crop protectants. The secondary metabolism of fungi represents an attractive and by far not fully exploited source of substances with interesting biological properties.

In close collaboration with the Institute of Biotechnology and Drug Research (IBWF) in Kaiserslautern, we elucidate the structures of novel fungal metabolites by various spectroscopic methods. Our group is involved in the Rhineland-Palatinate Center for Natural Product Research which also includes two industrial patners. A further aspect of our work is the determination of biogenetic pathways either by preparation of suitably labeled precursors or by 13C-NMR spectroscopy.

Sweet (Hetero)aromatics: Glycosylated templates as potential saccharide mimetics

Structurally defined oligosaccharides play an important role in the communication between cells in higher organisms. Prominent examples are the blood group antigens which allow the differentiation between erythrocytes of different species and even between different individuals or the sialyl LewisX tetrasaccharide which is involved in the recruitment of leukocytes within the inflammatory cascade. Mono- and diglycosylated aromatics as well as heteroaromatics may serve as metabolically stable mimetics of di- and trisaccharides. In our group, we investigate methods for their preparation from monosaccharidic building blocks e.g. by direct C-glycosylation, alkyne hydroamination or Larock cyclization.

Synthesis of natural products

We developed syntheses of various polycyclic alkaloids, among them a highly enantioselective access to the phenanthroindolizidine (S)-Tylophorine which has been demonstrated to possess a wide range of biological activities. For instance, it has been shown to be a potent inhibitor of eukaryotic protein biosynthesis and to inhibit RNA-transcription as well as the action of several cyclins regulating the cell cycle.

For the preparation of the racemic alkaloid, a short synthesis based on the Stevens rearrangement of a nitrile-stabilized ammonium ylide has been developed. It comprises only five linear steps two or even three which can be performed in a one-pot procedure. Moreover, it requires no chromatographic purifications.

The chemistry of deprotonated α-aminonitriles in combination with Noyori`s asymmetric transfer hydrogenation allows the preparation of dimeric benzylisoquinolines such as tetramethylmagnolamine. In this case, the Ullmann diarylether synthesis was chosen to couple both benzylisoquinoline units.