Synthetic studies directed towards asmarines and other purines with fused heterocyclic systems

Nature is a rich source of bioactive compounds and potential drugs. The so-called secondary metabolites are structures involved in interaction between organisms, for instance chemical defense. Studies of such metabolites have led to the discovery of many life-saving drugs, including antibiotics, immunosuppressant and antineoplastic agents. The last 50 years there has been an increasing interest for marine natural products as potential drugs and molecular tools, since an enormous chemical and biological di versity are found among metabolites from marine species. However, most bioactive marine products can only be isolated in very minute amounts, and bioprospecting must be combined with state of the art organic synthesis in order to explore the true potentia l of these chemically complex structures. Organic synthesis also open up the possibilities for preparation of marine natural product analogs which may be easier to synthesize, and which may also possess improved properties regarding bioactivity, bioavaila bility etc. Asmarines have been isolated from marine sponges (Raspailia sp). Currently 11 asmarines are known, and asmarines A and B are reported to possess significant cytotoxic activity against various human cancer cell lines. This project is aiming at the first total synthesis of one or more asmarines, even though this overall goal may not be reached within this project period. Compounds synthesized will be evaluated as potential antimicrobials (against pathogenic bacteria, incl. mycobacteria, fungi a nd protozoa), and potential anti-cancer compounds. While working towards a total synthesis of one ore more asmarines, several analogs or model substances will be synthesized. Their antimicrobial and cytotoxic activity will be studied. This will lead to in creased knowledge regarding structure-activity relationships (SAR) for asmarines and analogs. In due course, potential antimicrobial or anti-cancer drugs with optimized structures compared to the parent natural pro