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1-C-phosphonomethyl- and 1-C-difluorophosphonomethyl-1,4-imino-L-arabinitols as Galf transferase inhibitors: A comparison

Abstract : The convenient preparation of iminopentitol derivatives, based on a 1,4-dideoxy-1,4-imino-l-arabinitol scaffold carrying β-phosphono(difluoromethyl) or β-phosphonomethyl appendages, as Galf-1P mimics, is reported. The compounds were tested for their ability to inhibit GlfT2, a vital galactofuranosyltransferase involved in the cell wall biosynthesis of mycobacteria. Interestingly, the Galf-1P mimics lacking a fluorine atom (7 and 8) were very poor inhibitors, showing less than 20% inhibition of GlfT2, whereas compounds 2 and 3, which contains a difluoromethylenephosphonate moiety were more potent inhibitors. Compound 3 that is fully deprotected was the most potent showing a significant IC50 value (0.9 mm), despite the absence of the diphosphate linkage present in the parent sugar nucleotide. This study paves the way to the synthesis of more complex β-phosphonomethyl-imino-l-arabinitol derivatives as simplified mimics of UDP-α-d-Galf.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02024489
Contributor : Madeleine Roux-Merlin <>
Submitted on : Tuesday, February 19, 2019 - 11:09:23 AM
Last modification on : Thursday, July 2, 2020 - 3:28:35 AM

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C. Cocaud, R.B. Zheng, T.L. Lowary, Thomas Poisson, Xavier Pannecoucke, et al.. 1-C-phosphonomethyl- and 1-C-difluorophosphonomethyl-1,4-imino-L-arabinitols as Galf transferase inhibitors: A comparison. Carbohydrate Research, Elsevier, 2018, 461, pp.45-50. ⟨10.1016/j.carres.2018.03.009⟩. ⟨hal-02024489⟩

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