SYNTHESIS AND BIOLOGICAL EVALUATION OF A NOVEL ACRONYCINE/DUOCARMYCIN HYBRID NATURAL PRODUCT

摘要

The design of novel natural product hybrids consisting of parts of two or more bioactive compounds may allow an access to new drugs. Here we describe the synthesis of 3, a hybrid of the cytotoxic acronycine (2) and seco-duocarmycin (seco-1), which was prepared via a selective bromination of 7 followed by the introduction of an alkyne moiety, which was further manipulated to give the epoxide 12. Cyclisation and chlorination of the formed primary hydroxy group yielded 3, which in situ would give the desired hybrid 4. The in-vitro-cytotoxicity test revealed a slightly higher bioactivity of the hybrid 3 compared to acronycine (2).