Synthesis of complex organohalogens from carbohydrates

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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.