Studies Towards the Formal and Total Syntheses of Ginkgolide Natural Products

银杏内酯天然产物的正式合成和全合成研究

• 批准号: 2758011
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2758011
• 关键词: Studies; Towards; Formal; Total; Syntheses

This project falls within the EPSRC Synthetic Organic Chemistry research area. Total synthesis is central to chemistry as a whole. By finding new ways to make complex molecules, chemists tackle problems which can have far reaching consequences in fields such as methodology, spectroscopy, structural analysis, and computational chemistry, among others. In particular, the total synthesis of naturally occurring molecules - natural products - allows for the discovery of new drug molecules and the development of medical treatments. For example, Newman and Cragg highlighted in a recent review that since the approval of the first anti-tumour agent in 1946 the majority of clinically approved small molecule anti-cancer agents has been derived from natural products. In this context, the current project will focus on the synthesis of the ginkgolide family of natural products. Extracts from the Ginkgo biloba tree, found in China, have shown promise in the treatment of central nervous system disorders - multiple sclerosis, Parkinson's, Alzheimer's - as well as less severe cognitive ailments; e.g., tinnitus and migraines. It is believed that the ginkgolides, originally isolated in 1932, are key to the therapeutic potential of these extracts. As such, they are a relevant class of molecules and bear investigating. The aim of this project is to complete a novel formal synthesis of ginkgolide B and to investigate the potential for asymmetric syntheses of the remaining ginkgolide natural products. There will be a focus on economy of steps, improving on previously reported syntheses. Structurally, the ginkgolides are highly complex and pose a significant synthetic challenge. The main sources of this complexity are the numerous contiguous stereocentres and the presence of a tertiary-butyl group - a rarity in natural products. Therefore, this project offers the possibility of developing new strategies and methodologies as well as leveraging previously developed reactions in new ways. Finally, the successful synthesis of the ginkgolides will allow the investigation of derivatives as potential pharmaceuticals.

该项目属于EPSRC合成有机化学研究领域。总合成是整个化学的核心。通过寻找新的方法来制造复杂的分子，化学家解决了在方法论，光谱，结构分析和计算化学等领域可能会产生遥远后果的问题。特别是，天然存在的分子的总合成 - 天然产物 - 可以发现新药分子和医疗治疗的发展。例如，纽曼（Newman）和克拉格（Newman）和克拉格（Cragg）在最近的一项评论中强调了自1946年第一种抗肿瘤剂的批准以来，大多数临床批准的小分子抗癌药物已从天然产物中得出。在这种情况下，当前的项目将集中于Ginkgolide天然产品家族的综合。在中国发现的银杏叶树的提取物在中枢神经系统疾病的治疗中表现出了希望 - 多发性硬化症，帕金森氏症，阿尔茨海默氏症 - 以及不太严重的认知疾病；例如耳鸣和偏头痛。据信，最初于1932年分离出来的银杏是这些提取物具有治疗潜力的关键。因此，它们是一类相关的分子，并进行了研究。该项目的目的是完成新颖的Ginkgolide B形式合成，并研究其余Ginkgolide天然产物的不对称合成的潜力。将重点放在步骤的经济上，以改善先前报道的合成。从结构上讲，银杏是高度复杂的，构成了重大的合成挑战。这种复杂性的主要来源是众多连续的立体中心和三级丁基群的存在 - 天然产物的罕见性。因此，该项目提供了开发新策略和方法论的可能性，并利用先前以新方式发展的反应。最后，成功合成银葡萄剂将允许将衍生物作为潜在药物进行研究。