Chemoenzymatic Synthesis of Trehalosamine, an Aminoglycoside Antibiotic and Precursor to Mycobacterial Imaging Probes

Jessica M. Groenevelt; Lisa M. Meints; Alicyn I. Stothard; Anne W. Poston; Taylor J. Fiolek; David H. Finocchietti; Victoria M. Mulholand; Peter J. Woodruff; Benjamin M. Swarts

doi:10.1021/acs.joc.8b00810

Chemoenzymatic Synthesis of Trehalosamine, an Aminoglycoside Antibiotic and Precursor to Mycobacterial Imaging Probes

Jessica M. Groenevelt, Lisa M. Meints, Alicyn I. Stothard, Anne W. Poston, Taylor J. Fiolek, David H. Finocchietti, Victoria M. Mulholand, Peter J. Woodruff, Benjamin M. Swarts

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Abstract

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.

Original language	English
Pages (from-to)	8662-8667
Number of pages	6
Journal	Journal of Organic Chemistry
Volume	83
Issue number	15
DOIs	https://doi.org/10.1021/acs.joc.8b00810
State	Published - Aug 3 2018

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title = "Chemoenzymatic Synthesis of Trehalosamine, an Aminoglycoside Antibiotic and Precursor to Mycobacterial Imaging Probes",

abstract = "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.",

author = "Groenevelt, {Jessica M.} and Meints, {Lisa M.} and Stothard, {Alicyn I.} and Poston, {Anne W.} and Fiolek, {Taylor J.} and Finocchietti, {David H.} and Mulholand, {Victoria M.} and Woodruff, {Peter J.} and Swarts, {Benjamin M.}",

note = "Funding Information: This work was funded by a grant from the National Institutes of Health (R15 AI117670). Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

month = aug,

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doi = "10.1021/acs.joc.8b00810",

language = "English",

volume = "83",

pages = "8662--8667",

journal = "Journal of Organic Chemistry",

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T1 - Chemoenzymatic Synthesis of Trehalosamine, an Aminoglycoside Antibiotic and Precursor to Mycobacterial Imaging Probes

AU - Groenevelt, Jessica M.

AU - Meints, Lisa M.

AU - Stothard, Alicyn I.

AU - Poston, Anne W.

AU - Fiolek, Taylor J.

AU - Finocchietti, David H.

AU - Mulholand, Victoria M.

AU - Woodruff, Peter J.

AU - Swarts, Benjamin M.

PY - 2018/8/3

Y1 - 2018/8/3

N2 - 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.

AB - 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.

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JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

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ER -

Chemoenzymatic Synthesis of Trehalosamine, an Aminoglycoside Antibiotic and Precursor to Mycobacterial Imaging Probes

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