Roquefortine C was isolated from a variety of Penicillium roqueforti cultures, as well as in a variety of food products like blue cheese, moulded grain, etc. Roquefortine C received attention because of its neurotoxicity, which is still not clear because of the inconsistent toxicity data reported. In order to complete a first total synthesis of roquefortine C, new amidation methods to make the key amide bond were investigated. A novel synthetic strategy to construct the E-dehydrohistidine moiety is described.