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Synthesis 2022; 54(12): 2916-2926
DOI: 10.1055/a-1764-8950
paper

Functionalized d- and l-Arabino-Pyrrolidines as Potent and Selective Glycosidase Inhibitors

Marianne B. Haarr
a   Faculty of Science and Technology, Department of Chemistry, Bioscience, and Environmental Engineering, University of Stavanger, Kristine Bonnevies vei 22, 4021 Stavanger, Norway
,
Óscar Lopéz
b   Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, C/ Profesor García González, 1, 41012 Sevilla, Spain
,
Jóse G. Fernández-Bolaños
b   Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, C/ Profesor García González, 1, 41012 Sevilla, Spain
,
Emil Lindbäck∗
a   Faculty of Science and Technology, Department of Chemistry, Bioscience, and Environmental Engineering, University of Stavanger, Kristine Bonnevies vei 22, 4021 Stavanger, Norway
,
Magne O. Sydnes∗
a   Faculty of Science and Technology, Department of Chemistry, Bioscience, and Environmental Engineering, University of Stavanger, Kristine Bonnevies vei 22, 4021 Stavanger, Norway
› Author AffiliationsThe authors acknowledge the ToppForsk program at the Universitetet i Stavanger (University of Stavanger) for financial support and the provision of a Ph.D. fellowship to M.B.H. (PR-10550). O.L. and J.G.F.B. are grateful to the Ministerio de Ciencia e Innovación funded by MCIN/AEI/10.13039/501100011033 (PID2020-116460RB-I00) and Junta de Andalucía (FQM-134).
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Abstract

The efficient synthesis of enantiomeric pairs of iminosugars including 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) and 1,4-dideoxy-1,4-imino-l-arabinitol (LAB) analogues with an amidine, hydrazide, hydrazide imide, or amide oxime moiety is described. The preparation of DAB and LAB analogues commenced from l-xylose and d-xylose, respectively. The obtained iminosugars are tested against a panel of glycosidases with pharmaceutical relevance, revealing enhanced activity for the DAB analogues in comparison with the LAB analogues. In particular, the d-arabino-configured amidine behaved as a potent (submicromolar range) and selective inhibitor of α-mannosidase.

Key words

iminosugars - glycosidase inhibitors - arabino - pyrrolidine - mannosidase

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1764-8950.
  • Supporting Information


Publication History

Received: 12 January 2022

Accepted after revision: 07 February 2022

Accepted Manuscript online:
07 February 2022

Article published online:
05 April 2022

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