The total synthesis of lodopyridone

• Main Author: George, Ian R.
• Published: University of Nottingham 2013
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663246

Natural products are an important and diverse class of compounds; pyrones and pyridones, examples of their chemistry and natural products featuring these structures are discussed. Lodopyridone (75) is introduced as both a highly unusual natural product and a potential NQ02 inhibitor. A number of simple lodopyridone inspired analogues were prepared as potential NQ02 inhibitors and tested for binding to the enzyme. Synthetic studies toward lodopyridone featuring acetylation, rearrangement and cross coupling approaches to the key C-6 C-C bond formation were explored. Pyrone 175 was prepared by Suzuki coupling and oxidation studies towards amide 189, featuring a key modified Corey-Ganem-Gilman reaction were explored. The key pryone 189 was converted to the pyridone 196 and manipulation to complete the synthesis of lodopyridone (75) was achieved. Studies towards the related pyridone containing natural product antibiotic B 90063 were performed and a synthetic strategy presented. Conclusion in Chapter 3 and future work in Chapter 4 is presented followed by full experimental procedures in Chapter 5.