Towards a Concise Total Synthesis of the Antitumour Agent, (+)-Eremantholide A

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The fundamental objective of this research programme is to develop a short asymmetric synthesis of the antitumour sesquiterpenoid, (+)-eremantholide A, using a novel 4-component coupling strategy.Almost 30 years has elapsed since (+)-eremantholide was last examined as an antitumour drug, and even then, it was only profiled against a single human KB nasopharyngeal cancer cell line. Although it was found to have pronounced growth inhibitory effects , it was never tested against other human tumour cell lines, nor was it evaluated for antitumour efficacy (or toxicity) in rodent tumour models. A new and highly efficient synthesis of (+)-eremantholide A could provide enough material to permit a more thorough antitumour evaluation to take place, which could possibly allow a new antitumour target to be identified or validated.Analogue work on this lead has never previously been carried out due to the very lengthy syntheses of this compound that have so far been developed. Our programme is specifically focused upon developing a short synthesis that will allow analogue construction to easily take place. This will greatly assist future efforts to explore the chemical biology of this lead and its analogues. It could also permit the development of new and more potent antitumour drugs based on this lead structure.