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。全合成是整个化学的核心。通过寻找制造复杂分子的新方法，化学家解决了可能在方法学、光谱学、结构分析和计算化学等领域产生深远影响的问题。特别是，天然存在的分子（天然产物）的全合成使得新药物分子的发现和医学治疗的开发成为可能。例如，Newman 和 Cragg 在最近的一篇综述中强调，自 1946 年批准第一种抗肿瘤药物以来，大多数临床批准的小分子抗癌药物均来自天然产物。在此背景下，当前项目将重点关注银杏内酯家族天然产物的合成。在中国发现的银杏树提取物在治疗中枢神经系统疾病（多发性硬化症、帕金森病、阿尔茨海默病）以及不太严重的认知疾病方面显示出了前景；例如，耳鸣和偏头痛。据信，银杏内酯最初于 1932 年分离出来，是这些提取物治疗潜力的关键。因此，它们是一类相关的分子，值得研究。该项目的目的是完成银杏内酯 B 的新型形式合成，并研究其余银杏内酯天然产物的不对称合成潜力。将重点关注步骤的经济性，改进先前报道的合成。从结构上来说，银杏内酯非常复杂，给合成带来了巨大的挑战。这种复杂性的主要来源是众多连续的立构中心和叔丁基的存在——这在天然产物中很少见。因此，该项目提供了开发新策略和方法以及以新方式利用先前开发的反应的可能性。最后，银杏内酯的成功合成将有助于研究其衍生物作为潜在的药物。