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Article Dans Une Revue Organic & Biomolecular Chemistry Année : 2019

Synthesis and glycosidase inhibition of conformationally locked DNJ and DMJ derivatives exploiting a 2-oxo- C -allyl iminosugar

Résumé

The synthesis and glycosidase inhibition profile of a series of bicyclic analogs of DNJ and DMJ displaying a similar hydroxyl pattern and a distinct conformation is described.
A series of analogs of the iminosugars 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ), in which an extra five or six-membered ring has been fused to the C1-C2 bond have been prepared. The synthetic strategy exploits a key 2-keto-C-allyl iminosugar, easily accessible from gluconolactam, which upon Grignard addition and RCM furnishes a bicyclic scaffold that can be further hydroxylated at the C[double bond, length as m-dash]C bond. This strategy furnished DNJ mimics with the piperidine ring locked in a 1C4 conformation with all substituents in axial orientation when fused to a six-membered ring. Addition of an extra ring to DNJ and DMJ motif proved to strongly modify the glycosidase inhibition profile of the parent iminosugars leading to modest inhibitors. The 2-keto-C-allyl iminosugar scaffold was further used to access N-acetylglycosamine analogs via oxime formation.

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Chimie
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Dates et versions

hal-04418307 , version 1 (25-01-2024)

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Quentin Foucart, Yuna Shimadate, Jérôme Marrot, Atsushi Kato, Jérôme Désiré, et al.. Synthesis and glycosidase inhibition of conformationally locked DNJ and DMJ derivatives exploiting a 2-oxo- C -allyl iminosugar. Organic & Biomolecular Chemistry, 2019, 17 (30), pp.7204-7214. ⟨10.1039/c9ob01402k⟩. ⟨hal-04418307⟩
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