Studies Towards the Total Synthesis of Eleutherobin and Designed Analogues for Cancer Therapy

Cancer is one of the leading causes of death among Canadians, and therefore the identification of new cancer therapies is of great importance. To that end, researchers have found that the structurally diverse defence chemicals provided by sessile marine organisms offer great potential in the fight against cancer. In fact, in the past decade more than 30 natural products isolated from marine sources have entered preclinical and clinical trials as potential treatments for cancer. However, it is rarely ecologically or economically feasible to obtain the active ingredient by harvesting the natural source. Fortunately, synthetic organic chemistry - where molecules are fabricated in the laboratory through a series of chemical transformations - can serve as an alternative source of these compounds. Eleutherobin was originally isolated from a rare soft coral located of the coast of Western Australia in 1997, and in preliminary tests it has shown many promising anti-cancer properties. In fact, taxol, a member of the same class of agents, has already been used to treat more than one million patients suffering from advanced breast and ovarian cancers. Over the past two years, Jeffrey Mowat has spearheaded research centered on the development of a concise synthesis of eleutherobin and analogues of this substance as candidates for cancer treatment. However, so far, eleutherobin's preclinical evaluation has been hampered by lack of material from the natural source or chemical synthesis. Mr. Mowat's current research project addresses this situation through the development of a synthetic strategy that would significantly reduce the number of steps required to access eleutherobin and facilitate its preclinical evaluation. His research also provides a venue for the construction of analogues of eleutherobin, the biological evaluation of which may well lead to the discovery of new, improved antimitotic drugs for cancer therapy.