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

所述双甲内酯是从从双沟藻属（Amphidinium）的共生甲藻中提取的大环内酯类天然产物，所述共生甲藻从双沟藻属（Amphiscolops）物种的冲绳扁虫中培养。迄今为止，已经分离出这类天然产物的30多个成员，并已报道了它们对人类癌细胞系的细胞毒性。尽管这一不同大环内酯类的几个成员已显示出强的细胞毒性并具有其他生物活性，但在大多数情况下，为了充分确定其治疗潜力所需的大量材料是不可用的。拟议的研究计划的目标是设计和实施有效的全合成Ampidinolides C，C2，C3和F，这将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。新的反应和合成策略将被采用，以使目标化合物的合成以收敛和简洁的方式完成。旨在使两亲性内酯F和两亲性内酯C、C2、C3的合成路线既模块化又高度收敛，以最小化合成步骤并最大化天然产物的总产率。

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.