Natural Product Synthesis and Synthetic Methodology

天然产物合成及合成方法

• 批准号: RGPIN-2014-05137
• 负责人: Boukouvalas, John
• 金额: $ 2.48万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632777
• 关键词: Natural; Product; Synthesis; Synthetic; Methodology

Natural products are inherently optimized for biological interactions and occupy chemical space distinct from that of most synthetic molecules. As such they represent an unparalleled source of inspiration for advances in organic chemistry and disease treatment. We regard natural products not only as valuable commodities per se, but also as a driving force for invention of new and enabling synthetic technologies of broader scope. Hence, the proposed work aims at streamlining target-oriented synthesis and the development of powerful new methods and strategies for constructing privileged structures. The targets are functionalized oxacycles (lactones, tetrahydrofurans, gamma-pyrones and cyclic peroxides) having unusual structural features and highly sought biological properties, including antitumor, anti-inflammatory and antimalarial activities. Each target instills specific challenges that provide ample opportunity for addressing key issues such as selectivity, step-economy and overall efficiency. Some of them (e.g. anomaxins A-B, donnaienin A and paracaseolide A) also provide a testing ground for some new reactions discovered very recently in my laboratories. Students who carry out this research develop problem-solving skills along with extensive expertise in synthetic organic chemistry. Nearly all members of my group further benefit through active participation in collaborative research on heterogeneous asymmetric catalysis, which involves a combination of surface science, organic synthesis and computational chemistry. Thus, broad-based training in an interdisciplinary setting is ensured.

天然产物本质上是优化的生物相互作用，并占据化学空间不同于大多数合成分子。因此，它们代表了有机化学和疾病治疗进步的无与伦比的灵感来源。我们不仅将天然产品视为有价值的商品本身，而且还将其视为发明新的和更广泛的合成技术的驱动力。因此，拟议的工作旨在简化目标导向的合成和强大的新方法和战略的发展，构建特权结构。目标是功能化的氧杂环（内酯、四氢呋喃、γ-吡喃酮和环状过氧化物），具有不寻常的结构特征和高度追求的生物特性，包括抗肿瘤、抗炎和抗疟疾活性。每一个具体目标都提出了具体的挑战，为解决选择性、逐步节约和总体效率等关键问题提供了充分的机会。其中一些（例如anomaxins A-B，donnaienin A和paracaseetrin A）也为我的实验室最近发现的一些新反应提供了试验场。开展这项研究的学生沿着在合成有机化学方面的广泛专业知识，培养解决问题的能力。几乎所有的小组成员都通过积极参与多相不对称催化的合作研究而进一步受益，这涉及表面科学，有机合成和计算化学的结合。因此，确保了在跨学科环境中进行基础广泛的培训。