Synthesis of phorbazoles and breitfussins analogues

Abstract

Breitfussins are a group of a closely related heterocyclic compounds. They consist of a tetracyclic structure with an indole, an oxazole and a pyrrole. The breitfussins exhibit interesting biological activity and analogues synthesis and biological evaluation is ongoing. Phorbazoles have a structural similarity with breitfussins in which a phenol replaces the indole. As a part of this, synthesis of phorbazoles, breitfussins and analogues is underway in the Bayer group. This thesis contains a description for the work done to synthesis a small library of a small group of phorbazoles analogues and one breitfussins analogue. During the synthesis of the phorbazoles analogues, an isocyanide based oxazole synthesis was performed using TosMIC. Iodination of the oxazole was tested with different approaches to obtain 2,4-diiodinated and 2-iodinated oxazole derivatives. For introducing a Pyrrole on the oxazole, a Suzuki-Miyaura cross coupling reaction was performed. As a final step, selective de-protections were performed to obtain the diversity of the analogues. The breitfussins analogue was formed in 2 steps from the commercially available starting material, methyl-1H-indole-3-carboxylate 13.