natural product synthesis, alkoxyallenes, cyclopropanes, multicomponent reactions to heterocycles, samarium diiodide induced transformations, palladium catalysis, functional and fluorinated heterocycles, 1,2-oxazines, alkenyl nonaflates, glycosidase inhibitors, carbohydrate and peptide mimetics, multivalent carbohydrate mimetics and heterocycles
The research in our group spans the field of organic chemistry from mechanistic studies to synthetic methodology and the synthesis of natural products as well as of structurally intriguing heterocyclic compounds. The central focus of the research is the design of new methods for the synthesis of bioactive and synthetically versatile compounds. We have a series of collaborations to evaluate our target molecules with teams of biochemists or physicists. As a result, our work involves a wide range of expertise in organic synthesis, heterocyclic chemistry, asymmetric synthesis and organometallic chemistry:
- lithiated alkoxyallenes are extremely versatile building blocks that have both nucleophilic and electrophilic centres. By taking advantage of this property highly functionalized heterocycles can be synthesized. We currently focus on the synthesis of enantiopure furan, pyrrole, 1,2-oxazine and spiroketal derivatives. Target compounds are glycosidase inhibitors, carbohydrate mimetics, aminosugar derivatives and rare monosaccharides. It was found that gold nanoparticles decorated with sulfated carbohydrate mimetics are extremely good multivalent selectin ligands with IC50 values in the subnanomolar range.
- new multicomponent reactions with lithiated alkoxyallenes as crucial precursor lead to novel highly substituted pyridine, pyrimidine and oxazole derivatives. The substitution pattern of these substrates allows us to selectively couple each molecule via metal-catalyzed coupling reactions in order to synthesize a variety of nano-sized oligoaryl-hetaryl conjugates as well as novel bipyridine and terpyridine derivatives. Multivalent heterocyclic moieties are also constructed to study their properties on graphite and metal surfaces by STM and SMF.
- samarium diiodide is an electron-transfer reagent for chemo- and stereoselective carbon-carbon bond formation. We take advantage of this reactivity to synthesize steroid analogues, some of which have shown desired biological activity. We have also demonstrated that this reagent can be successfully used for the synthesis of highly substituted indole and pyrrole derivatives as well as a variety of medium-sized (7-, 8- and 9-membered) rings. These efforts culminated in a short and extremely efficient total synthesis of the magic natural product strychnine.
- Another aspect of our research focuses on the synthesis of peptide analogues using methodology developed earlier in our group. Starting from donor-acceptor-substituted cyclopropanes in the presence of sulfur and CH-acidic components we are able to generate thiophene-derived amino acids (Gewald reaction), which share isosteric properties with natural dipeptides. These building blocks can be used in the synthesis of novel macrocycles as well as peptidomimetics.
- alkenyl and (het)aryl nonaflates are very useful intermediates for cross-coupling reactions. Although slightly more reactive compared to the related triflates they are more stable and available through selective and inexpensive methods. Palladium catalyzed reactions provide very useful coupling products, in particular novel pyridine derivatives as well as polycyclic compounds.