Chemoenzymatic Synthesis of Trehalosamine, an Aminoglycoside Antibiotic and Precursor to Mycobacterial Imaging Probes
The Journal of Organic Chemistry
Trehalosamine (2-amino-2-deoxy-α,α-d-trehalose) is an aminoglycoside with antimicrobial activity against Mycobacterium tuberculosis, and it is also a versatile synthetic intermediate used to access imaging probes for mycobacteria. To overcome inefficient chemical synthesis approaches, we report a two-step chemoenzymatic synthesis of trehalosamine that features trehalose synthase (TreT)-catalyzed glycosylation as the key transformation. Soluble and recyclable immobilized forms of TreT were successfully employed. We demonstrate that chemoenzymatically synthesized trehalosamine can be elaborated to two complementary imaging probes, which label mycobacteria via distinct pathways.
Groenevelt, J.M,, Meints, L.M,, Stothard, A.I,, Poston, A.W., Fiolek, T.J., Finocchietti, D.H., Mulholand, V.M., Woodruff, P.J., Swarts, B.M. (2018). Chemoenzymatic synthesis of trehalosamine, an aminoglycoside antibiotic and precursor to mycobacterial imaging probes. The Journal of Organic Chemistry. 83(15), 8662-8667. doi: 10.1021/acs.joc.8b00810