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Issue 6, 2012
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Synthesis and enzymatic evaluation of ketose phosphonates: the interplay between mutarotation, monofluorination and acidity

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Abstract

Ketose-phosphonates may adopt open chain, or α- or β-furanosyl, or α- or β-pyranosyl configurational isomers in aqueous solution. An HPLC and NMR analysis of a series of ketose-phosphonates with a thymidylyltransferase (dTDP-glucose pyrophosphorylase) implied a rapid dynamic equilibrium between the pyranosyl forms of gluco-ketose phosphonate leading to efficient production of unique sugar nucleotide analogues. The preparation of diastereomerically pure gluco-configured monofluoromethylenephosphonates enabled the determination of the thymidylyltransferase preference for CHF stereochemistry. The effects of acidity upon thymidylyltransferase substrate specificity were determined using a series of monofluoro- and difluoro- ketose-phosphonates. WaterLOGSY NMR spectroscopy demonstrated a switching of the ordered Bi-Bi mechanism with ketose-phosphonate substrates. Ketose-phosphonates are presented as a unique class of sugar 1-phosphate analogues with potential applications as glycosyltransferase probes.

Graphical abstract: Synthesis and enzymatic evaluation of ketose phosphonates: the interplay between mutarotation, monofluorination and acidity

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Publication details

The article was received on 19 Dec 2011, accepted on 16 Mar 2012 and first published on 16 Mar 2012


Article type: Edge Article
DOI: 10.1039/C2SC01077A
Citation: Chem. Sci., 2012,3, 1866-1878
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    Synthesis and enzymatic evaluation of ketose phosphonates: the interplay between mutarotation, monofluorination and acidity

    S. M. Forget, D. Bhattasali, V. C. Hart, T. S. Cameron, R. T. Syvitski and D. L. Jakeman, Chem. Sci., 2012, 3, 1866
    DOI: 10.1039/C2SC01077A

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