Mersacidin forms a complex with Lipid II which in turn inhibits the transglycosylation pathway to cell wall biosynthesis. The CD bicyclic unit seems to be involved in the binding mode with Lipid II. However, the nature of this interaction remains unknown. Structure-activity relationship studies on the mode of action of Mersacidin and its derivatives not only would elucidate its mechanism of action, but may also contribute to the rational design of new lead compounds. Therefore, the synthesis of Mersacidin is of great importance.
We have successfully synthesized a D-ring derivative which contains the sensitive (Z)-aminovinyl cysteine linkage, a feature that has not been observed within the structure of a polypeptide ring. The knowledge we have gained through the synthesis of the D-ring will in turn guide us through the synthesis of the complex CD-ring.
This project have involved the design and execution of multistep organic syntheses, the purification of intermediates by chromatographic methods (flash chromatography, preparative LC, analytical HPLC), and the identification of organic structures by analytical techniques (NMR, FT-IR, LC/MS, HR/MS).
Currently, we are investigating the orthogonal construction of each ring as well as the sensitive (Z)-aminovinyl cysteine linkage. Our efforts towards these aims will be presented.