Synthesis of chemical tools to label the mycomembrane of corynebacteria using modified iron() chloride-mediated protection of trehalose

• Published in: Organic & biomolecular chemistry 2022-03, Vol.2 (9), p.1974-1981
• Main Authors: Carlier, Mathieu, Lesur, Emilie, Baron, Aurélie, Lemétais, Aurélie, Guitot, Karine, Roupnel, Loïc, Dietrich, Christiane, Doisneau, Gilles, Urban, Dominique, Bayan, Nicolas, Beau, Jean-Marie, Guianvarc'h, Dominique, Vauzeilles, Boris, Bourdreux, Yann
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Cell Membrane - drug effects; Chemical Sciences; Chemical synthesis; Chlorides - chemistry; Chlorides - pharmacology; Corynebacterium - drug effects; Disaccharides; Ferric chloride; Ferric Compounds - chemistry; Ferric Compounds - pharmacology; Fluorescent indicators; Hydroxyl groups; Labeling; Microbial Sensitivity Tests; Organic chemistry; Other; Probes; Trehalose; Trehalose - chemical synthesis; Trehalose - chemistry; Trehalose - pharmacology
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d2ob00107a

Trehalose-based probes are useful tools that allow the detection of the mycomembrane of mycobacteria through the metabolic labeling approach. Trehalose analogues conjugated to fluorescent probes can be used, and other probes are functionalized with a bioorthogonal chemical reporter for a two-step labeling approach. The synthesis of such trehalose-based probes mainly relies on the desymmetrization of natural trehalose using a large number of regioselective protection-deprotection steps to differentiate the eight hydroxyl groups. Herein, in order to avoid these time-consuming steps, we reinvestigated our previously reported tandem protocol mediated by FeCl 3 ·6H 2 O, with the aim of modifying the ratio of the products to allow the challenging desymmetrization of the C 2 -symmetrical disaccharide trehalose. We demonstrate the usefulness of this method in providing easy access to trehalose analogues with a bioorthogonal moiety or a fluorophore in C-2, and also present their use in a one-step and two-step labeling approach, either of which can be used to study the mycomembrane in live mycobacteria. Regioselective protection of trehalose allows the fast synthesis of chemical tools for the study of the mycomembrane.