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

本研究计划的基本目标是开发一个简短的不对称合成的抗肿瘤倍半萜类化合物，（+）-eremanthropine A，使用一种新的4-组分coupling strategy.Almost 30年过去了，因为（+）-eremanthropine最后一次被检查作为一种抗肿瘤药物，即使在那时，它只是针对一个单一的人KB鼻咽癌细胞系的配置文件。虽然发现它具有显著的生长抑制作用，但从未对其他人类肿瘤细胞系进行过测试，也没有在啮齿动物肿瘤模型中评估其抗肿瘤功效（或毒性）。一个新的和高效的合成（+）-eremanthropic A可以提供足够的材料，允许一个更彻底的抗肿瘤评价发生，这可能会允许一个新的抗肿瘤靶点被识别或validated. Anesthetic工作在此之前从未进行过，由于非常漫长的合成这种化合物，迄今已开发。我们的计划是专门专注于开发一个简短的合成，将允许模拟建设很容易发生。这将极大地有助于未来探索这种铅及其类似物的化学生物学的努力。它还可以允许基于这种先导结构开发新的和更有效的抗肿瘤药物。

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.