The synthesis and biological evaluation of novel derivatives from the hop component Humulone

Hops have been used in the brewing of alcoholic beverage for over 3000 years. Due to new consumer preferences towards sweeter drinks or 'Alcopops', beer consumption has taken a drastic decline. This has caused the economic value of hops as a commodity to decline, therefore new applications for this material are required. The hop extracts humulone (8) and lupulone (22) exist in several tautomeric forms. We present unequivocal evidence for the existence of the major tautomer of lupulone, colupulone and a derivative of humulone in polar media. The evidence has been obtained from single X-ray crystallographic data and computer modelling as well as IH and 13e NMR spectroscopy. The first 2D INADEQUATE spectrum of the tautomer of lupulone provides unambiguous chemical shift assignments for all of the structural carbon atoms. This project has also involved the investigation into known and novel derivatives of the major constituents of hops, humulone (8) and lupulone (22), as possible bactericides. The main mode of action of these compounds activity against bacterial cells is their ability to chelate metal ions and allow passive diffusion of these complexes out of cells. A number of chemical derivatives have been synthesised and, using a model developed as part of this research, tested for their potential to pass metal ions from aqueous to non-polar organic media. In addition to this some of the novel compounds have been screened on bacterial samples to determine the structure activity relationship of the known and novel derivatives. Chapter 1 covers the background ofhumulone (8) and the hop acids. Chapter 2 covers the biology ofthe hop acids including biological activity. Chapter 3 covers the structural analysis of the hop acids. collected during this project and the derivatisation work. Chapter 4 covers the physical property data and biological data collected during this project. Chapter 5 gives a brief summary of the achievements of this project and future directions. Chapter 6 covers the experimental techniques and collected data