Synthesis of complex organohalogens from carbohydrates

原始有机卤素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，因为它们在合成方面存在挑战。本提案提出了最先进的有机卤素合成方法，并拓宽了他们的反应性，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显著高影响潜力的主要研究主题上：1)利用立体控制策略制备多邻有机卤素2)合成药学上相关的卤代杂环3)探索复杂卤化碳水化合物合成的新领域作为中短期项目，我们将解决合成和转化含氟醛多邻卤代烷的方法不足。下一步，我们将处理氯磺酸类似物的全合成。随着获得复杂的多邻卤素，关键的物理性质（构象和亲脂性）和生物活性将被评估。另一个中期目标是通过碳水化合物的方法获得大量的卤化杂环化合物。将特别关注氟化哌啶，探索关键的物理性质，如溶液态构象、亲脂性和胺碱性。我们的长期目标是制备一个大的卤化杂环文库和合成潜在的生物活性化合物。我们还建议解决复杂氟糖合成困难所带来的限制。特别是，我们希望改进相关的o -芳基卤代糖苷、卤代糖肽和低氟糖的合成。利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。在资助期结束时，我们的团队将通过开发具有独特性质的新型化学实体，将卤化碳水化合物和相关化合物带入新的领域。

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.