Mycobacterium tuberculosis, the etiological agent of human tuberculosis, requires the non-mammalian disaccharide trehalose for growth and virulence. Detectable trehalose analogues have gained interest as probes to study trehalose metabolism and as potential diagnostic tools for the tuberculosis infection. Here, we report our progress toward the synthesis and conformational analysis of four 19F-deoxyfluoro trehalose (FluoroTre) analogues, along with the assessment of their uptake by the model organism, M. smegmatis. Using a one-step chemoenzymatic method, several of the FluoroTre analogues were rapidly synthesized and purified within 1 hour in high yield. One FluoroTre analogue, which could not be accessed chemoenzymatically, was chemically synthesized using a trehalose desymmetrization strategy. NMR and molecular modeling techniques were used for conformational analysis of the FluorotTre analogues, and a GC-MS assay was used to show investigate uptake by M. smegmatis. The efficiency of 19F-FluoroTre synthesis, purification, and administration to M. smegmatis described here may support future applications in using short-lived 18F-deoxyfluoro trehalose analogues as positron emission tomography (PET) probes for in vivo imaging of M. tuberculosis infection.

Synthesis and conformational analysis of fluorine-modified trehalose analogues

251st National Meeting (2016)

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