C-Nucleosides To Be Revisited

Clercq, Erik De

doi:10.1021/acs.jmedchem.5b01157

Cited by 163 publications

(131 citation statements)

References 99 publications

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“…The remarkable stereospecificity of this reaction coupled with its ability to provide C -glycosides, a class of compounds important in natural products [66] and drug design [67], makes this methodology a very powerful one. One very clear drawback, however, is the extremely laborious preparation of the glucosyl donors.…”

Section: Reviewmentioning

confidence: 99%

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

Downey

Hocek

2017

Beilstein J. Org. Chem.

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Glycosylation is an immensely important biological process and one that is highly controlled and very efficient in nature. However, in a chemical laboratory the process is much more challenging and usually requires the extensive use of protecting groups to squelch reactivity at undesired reactive moieties. Nonetheless, by taking advantage of the differential reactivity of the anomeric center, a selective activation at this position is possible. As a result, protecting group-free strategies to effect glycosylations are available thanks to the tremendous efforts of many research groups. In this review, we showcase the methods available for the selective activation of the anomeric center on the glycosyl donor and the mechanisms by which the glycosylation reactions take place to illustrate the power these techniques.

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Section: Reviewmentioning

confidence: 99%

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

Downey

Hocek

2017

Beilstein J. Org. Chem.

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“…C-nucleosides bearing pyrrolo[2,1-f ] [1,2,4]triazin-4-amine as nucleobase. While GS-6620 exhibits good activity against hepatitis C virus (HCV) infections, [5] GS-5734 is a potential drug for the treatment of the EBOV infection.…”

Section: Introductionmentioning

confidence: 99%

“…Successful examples that received marketing approval for clinical use include tenofovir, adefovir, and cidofovir. In particular, we planned to prepare C-nucleoside phosphonate analogue 1 (Figure 2) consisting of a L-threose sugar and pyrrolo [2,1-f ] [1,2,4]triazin-4-amine base moiety as model compound. To date, no examples have been reported in the literature of α-L-threosyl-C-nucleoside phosphonates.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a Threosyl‐C‐nucleoside Phosphonate

2019

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A general synthetic route for the preparation of the first analogue of a new series of sugar-modified C-nucleoside phosphonates is detailed. Such derivative contains a fourcarbon L-threose sugar moiety substituted with a phosphonomethoxy group at the 3′-position and pyrrolo[2,1-f ][1,2,4]triazin-4-amine as nucleobase. A C-nucleoside was initially prepared by coupling a benzyl protected L-threono-1,4-lactone intermediate with the corresponding aglycon moiety. The choice Eur.General Information: For all reactions, analytical grade solvents were used. All moisture sensitive reactions were carried out in ovendried glassware (120°C) under a nitrogen or argon atmosphere.

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“…[1] These latter C-nucleosides are naturally occurring and endowed with a lower enzymatic hydrolysis vulnerability of the C-C glycosidic bond with regard to the C-N bond of their natural and synthetic N-nucleosides analogs. These nucleosides could be called Nnucleosides and differ from C-nucleosides or non-canonical nucleosides where the heterocycle link to sugar is made up through a C-C bond.…”

Section: Introductionmentioning

confidence: 99%

Molecular modeling studies of pseudouridine isoxazolidinyl nucleoside analogues as potential inhibitors of the pseudouridine 5ʹ‐monophosphate glycosidase

et al. 2017

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In this paper, we investigated the hypothesis that pseudouridine isoxazolidinyl nucleoside analogues could act as potential inhibitors of the pseudouridine 5'-monophosphate glycosidase. This purpose was pursued using molecular modeling and in silico ADME-Tox profiling. From these studies emerged that the isoxazolidinyl derivative 1 5'-monophosphate can be effectively accommodated within the active site of the enzyme with a ligand efficiency higher than that of the natural substrate. In this context, the poor nucleofugality of the N-protonated isoxazolidine prevents or slows down, the first mechanistic step proposed for the degradation of the pseudouridine 5'-monophosphate glycosidase, leading to the enzyme inhibition. Finally, the results of the physicochemical and ADME-Tox informative analysis pointed out that compound 1 is weakly bounded to plasma protein, only moderately permeate the blood-brain barrier, and is non-carcinogen in rat and mouse. To the best of our knowledge, this is the first paper that introduces the possibility of inhibition of pseudouridine 5'-monophosphate glycosidase by a molecule that competing with the natural substrate hinders the glycosidic C-C bond cleavage.

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C-Nucleosides To Be Revisited

Cited by 163 publications

References 99 publications

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

Synthesis of a Threosyl‐C‐nucleoside Phosphonate

Molecular modeling studies of pseudouridine isoxazolidinyl nucleoside analogues as potential inhibitors of the pseudouridine 5ʹ‐monophosphate glycosidase

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