New Strategies for the Total Synthesis of Amphidinolide F and Amphidinolides C1-3

双环内酯类化合物是从双头水母属的共生甲鞭毛虫中提取的大环内酯类天然产物，是从双头水蚤的冲绳扁虫中培养出来的。到目前为止，已经分离出30多个这类天然产物的成员，并对其进行了表征，并报道了它们对人类癌细胞的细胞毒性。尽管这类不同的大环内酯类化合物中的几个成员已被证明具有强大的细胞毒性并具有其他生物活性，但在大多数情况下，充分确定其治疗潜力所需的大量材料是无法获得的。拟议的研究计划的目标是设计和实施有效的两性内酯C、C2、C3和F的全合成，为这些天然产物的全面生物学评价提供足够的材料，并作为快速制备简化类似物的平台。将采用新的反应和合成策略，使目标化合物的合成能够以收敛和简洁的方式完成。目的是合成两性内酯F和两性内酯C、C2、C3的合成路线将是模块化的和高度收敛的，以最大限度地减少合成步骤，并最大限度地提高天然产品的总收率。

The amphidinolides are macrolide natural products extracted from symbiotic dinoflagellates of the genus Amphidinium cultivated from the Okinawan flatworms of the Amphiscolops species. To date more than 30 members of this class of natural product have been isolated, characterised and their cytotoxicity against human cancer cell lines has been reported. Although several members of this diverse group of macrolides have been shown to exhibit potent cytotoxicity and possess other biological activities, in most cases the substantial quantities of material that would be required in order to fully establish their therapeutic potential are not available.The objective of the proposed research programme is the design and implementation of efficient total syntheses of amphidinolides C, C2, C3 and F that will provide sufficient material for full biological evaluation of these natural products and also serve as a platform for the rapid preparation of simplified analogues. New reactions and synthetic strategies will be employed to allow the syntheses of the target compounds to be accomplished in a convergent and concise manner. The intended that the synthetic route to amphidinolide F and amphidinolides C, C2, C3 will be both modular and highly convergent in order to minimise synthetic steps and maximise the overall yields of the natural products.