Conversion of Chemical Waste to Value-Added Fine Chemicals ? Biocatalytic Synthesis of Amaryllidaceae Alkaloids

Aromatic compounds can be isolated from crude oil in large quantities and are side-products in industrial processes. Because of their lack of reactivity, only few sophisticated large scale applications of these low-value products have been reported. The biocatalytic dihydroxy-lation of aromatics with soil bacteria is one rare but highly efficient exemption. This innovative process enantioselectively delivers chiral cyclohexadiene diols in good yield and constitutes an elegant method for the conversion of organic waste in valuable fine chemicals and pharmaceuticals. Despite the great potential of the combination of biocatalysis and traditional organic chemistry, only few research groups are actively engaged in this field and the dihydroxylation of aromatic acids has not been systematically evaluated to date. During the course of the project, the substrate scope of soil bacteria will be explored, with emphasis on aromatic carboxylic acids which have been neglected in previous studies. Different strains of bacteria (mainly Pseudomonas and Ralstonia species) will be employed in this survey to maximize the research output. These results will be of great importance for future synthetic projects. The main goal and major part of the current project is the utilization of the dihydroxylation product of benzoic acid (ipso,-ortho-diol) in the synthesis of lycorine-type Amayllidaceae alkaloids which show pronounced activity against human cancer cell lines. The proposed route takes advantage of novel synthetic methods to maximize the overall success. Although medicinally promising, Amaryllidaceae alkaloids are so far not accessible in large quantities from plants or existing synthetic routes. However, the stereochemical configuration of enzymatically derived cyclohexadiene diols makes them ideal starting materials and facilitates the large scale production of this important class of polyhydroxylated alkaloids. Final products and synthetic intermediates will be evaluated against human cancer cell lines and will serve as lead structure for the development of novel anticancer drugs. Summarizing, the proposed projects envisages the utilization of low-value side-products of the oil industry for the preparation of important Amaryllidaceae alkaloids with antitumor properties Furthermore, the project serves as feasibility study for future endeavors and the preparation of sophisticated polyhydroxylated targets with fascinating properties.