Synthesis of complex organohalogens from carbohydrates

从碳水化合物合成复杂的有机卤素

• 批准号: RGPIN-2022-04021
• 负责人: Giguere, Denis
• 金额: $ 2.62万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748677
• 关键词: Synthesis; complex; organohalogens; carbohydrates

The preparation of original organohalogens is a powerful strategy to discover novel chemical entities with unique properties. However, the chemistry and biology of complex organohalogens have not yet been exploited because of the synthetic challenges they present. This proposal presents state-of-the-art methods for the synthesis of organohalogens, and to broaden the collective knowledge of their reactivity, physical property, and biological activity. We intend to concentrate our efforts in the next five years in three major research themes with significant high-impact potential: 1) Exploiting stereocontrol strategies for the elaboration of multi-vicinal organohalogens 2) Synthesizing pharmaceutically relevant halogenated heterocycles 3) Exploring new frontiers in the synthesis of complex halogenated carbohydrates As a short- to medium-term project, we will address the lack of method for the synthesis and transformation of multi-vicinal halogenoalkanes having an fluoroaldehyde moiety. Moving forwards, we will tackle the total synthesis of chlorosulfolipid analogues. With access to complex multi-vicinal halogens, key physical properties (conformation and lipophilicity), and biological activities will be evaluated. Another medium-term objective is to access a large variety of halogenated heterocycles by using a carbohydrate approach. A special focus on fluorinated piperidines will be undertaken with exploration of key physical properties such as solution-state conformation, lipophilicity and amine basicity. Our long-term goal is the preparation of a large library of halogenated heterocycles and the synthesis of potentially bioactive compounds. We also propose to address limitations that arose from difficult synthesis of complex fluorosugars. In particular, we want to improve the synthesis of relevant O-aryl halogenoglycosides, halogenoglycopeptides, and fluorooligosaccharides. The discoveries that will be made using our carbohydrate approach will have a significant impact on organic chemistry and related sciences. By the end of the funding period, our team will have brought halogenated carbohydrates and related compounds to new frontiers by developing novel chemical entities with unique properties.

有机卤素化合物的制备是发现具有独特性质的新型化学实体的有力策略。然而，复杂有机卤素的化学和生物学尚未被开发，因为它们存在合成挑战。该提案提出了用于合成有机卤素的最先进的方法，并拓宽了其反应性，物理性质和生物活性的集体知识。我们打算在未来五年集中精力在三个具有重大影响潜力的主要研究主题上：1）开发立体控制策略用于多连位有机卤素的精细化2）合成药学上相关的卤代杂环3）探索合成复杂卤代碳水化合物的新前沿作为一个短期至中期项目，我们将解决缺乏合成和转化具有氟醛部分的多邻位卤代烷的方法的问题。展望未来，我们将解决氯硫脂类似物的全合成。通过获得复杂的多邻位卤素，将评估关键物理性质（构象和亲脂性）和生物活性。另一个中期目标是通过使用碳水化合物方法获得大量卤代杂环。特别关注氟化哌啶将进行关键的物理性质，如溶液状态的构象，亲油性和胺碱性的探索。我们的长期目标是制备一个大型卤代杂环化合物库，并合成具有潜在生物活性的化合物。 我们还建议解决复杂氟糖合成困难所带来的限制。特别是，我们希望改善相关的O-芳基卤代糖苷，卤代糖肽，和氟低聚糖的合成。使用我们的碳水化合物方法所取得的发现将对有机化学和相关科学产生重大影响。到资助期结束时，我们的团队将通过开发具有独特性质的新型化学实体，将卤代碳水化合物和相关化合物带到新的前沿。