ABSTRACT
In this article, we report the synthesis of sydnonimines from sydnones and their use as dipoles for fast click-and-release reactions. The process relies on nucleophilic aromatic substitution of aliphatic and aromatic amines with triflated sydnones. This new methodology allowed the preparation of functionalised sydnonimine probes that are otherwise difficult to prepare. These probes were then used to release a drug and a fluorescent aromatic isocyanate inside living cells.
Subject(s)
Sydnones , IsocyanatesABSTRACT
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 FeCl3·6H2O, with the aim of modifying the ratio of the products to allow the challenging desymmetrization of the C2-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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cell Membrane/drug effects , Chlorides/pharmacology , Corynebacterium/drug effects , Ferric Compounds/pharmacology , Trehalose/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Chlorides/chemistry , Ferric Compounds/chemistry , Microbial Sensitivity Tests , Trehalose/chemical synthesis , Trehalose/chemistryABSTRACT
In this study, we report the first synthesis of an alkyne-based trehalose monomycolate probe containing a ß-hydroxylated fatty acid and an α-branched chain similar to those of the natural mycolic acid. We demonstrate its utility for the labeling of the mycomembrane of Corynebacteria as well as for the study of mycoloyltransferases.
