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

Amphidinolide F 和 Amphidinolides C1-3 全合成新策略

• 批准号: 2305947
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2305947
• 关键词: New; Strategies; Total; Synthesis; Amphidinolide

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.

两足足内酯是从两足足属的共生双鞭毛虫中提取的大环内酯类天然产物，这些双鞭毛虫是从冲绳两足足属的扁虫中培养出来的。迄今为止，这类天然产物的30多个成员已被分离、表征，其对人类癌细胞系的细胞毒性已被报道。尽管这一多样化的大环内酯类化合物中的一些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，为了充分确立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两萜内酯C、C2、C3和F的全合成，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。将采用新的反应和合成策略，使目标化合物的合成以收敛和简洁的方式完成。两萜内酯F和两萜内酯C、C2、C3的合成路线将是模块化和高度收敛的，以尽量减少合成步骤，最大限度地提高天然产物的总产量。