Pancreatic cancer drugs: case studies in synthesis and production

Identification of bioactive compounds from natural sources represents only the first stage in the development process of some drugs. Plant and animal sources rarely produce bioactive compounds in the quantities required to meet commercial demands, thus the development of total or semi-synthetic routes to these materials becomes a core element of commercial drug production. This process brings to the table a plethora of issues that must be resolved to ensure the development of a safe, pure final product via economically feasible processes. Herein we discuss the synthesis of three anti-cancer drugs – 5-FU (6), gemcitabine (7) and paclitaxel (8) used in pancreatic cancer treatment. The synthetic approaches undertaken differ in each case, driven by factors such as structural complexity and physicochemical properties, which influence solubility and bioavailability. The chapter highlights the demanding nature of pharmaceutical research, covering a wide-range of issues from the exploration of reagents to maximise product outcomes in key synthetic steps, to the modification of intermediates to allow for large scale, nonchromatography based product purification. The work illustrates the long road and many false paths that exist between initial discovery and the ultimate development of a safe and commercially viable pharmaceutical product. While technological advancements in computer-based design, synthesis and screening techniques continue to accelerate drug development, success ultimately depends upon the intellect and creativity of dedicated teams of synthetic and formulation chemists in devising innovative solutions to resolving key impasses