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
© 2018 American Chemical Society
Electronic Supporting Information files are available without a subscription to ACS Web Editions. The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting Information. Files available from the ACS website may be downloaded for personal use only. Users are not otherwise permitted to reproduce, republish, redistribute, or sell any Supporting Information from the ACS website, either in whole or in part, in either machine-readable form or any other form without permission from the American Chemical Society. For permission to reproduce, republish and redistribute this material, requesters must process their own requests via the RightsLink permission system. Information about how to use the RightsLink permission system can be found at http://pubs.acs.org/page/copyright/permissions.html.