Total synthesis of the natural product brasilicardin A and synthesis of analogues of brasilicardin A as potent and selective compounds for use as immunosuppresives.

• Applicant: Professor Dr. Pierre Koch
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 184060691

Brasilicardin A, isolated from the cultured broth of the actinomycete Nocardia brasiliensis IFM0406, is a tricyclic terpenoid consisting of an anti/syn/anti-perhydrophenanthrene skeleton with a sugar moiety (a rhamnose, an N-acetylglucosamine, and 3-hydroxybenzoate) and an amino acid side chain. The target molecule has shown to exhibit immunosuppressive activity. In addition to its remarkable biological activity, brasilicardin A also possesses a synthetically challenging structure. This molecule has an unusual terpenoid structure since its tricyclic trans, syn, trans ABC ring structure requires ring B to be in a twist boat conformation. For this reasons, brasilicardin A is an intriguing natural product for both its impressive biological activity and its novel structural features. The aim is to achieve the total synthesis of brasilicardin A as well as to discover new compounds (analogues of brasilicardin A) which can be used as superior agents to avoid organ rejection after transplantation surgery. Therefore general methods for the synthesis of brasilicardin A will be developed and many analogues of brasilicardin A will be prepared. All of our synthetic analogues will be tested for their biological activity. Those biological results will allow establishing structure activity relationships and based on those results, further analogues will be prepared. The ultimate goal beside the completition of the total synthesis of brasilicardin A is to find selective and potent compounds for use as immunosuppressives.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Michael E. Jung