Stereoselective Methods in the Synthesis of Bioactive Oxathiolane and Dioxolane Nucleosides

D’Alonzo, Daniele; Guaragna, Annalisa

doi:10.1002/9781118498088.ch16

Cited by 6 publications

(7 citation statements)

References 146 publications

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“…Hence, the identification of new-generation chaperones, able to protect GAA from degradation without interfering with its activity (allosteric chaperones), is likewise being pursued . In this context, novel therapeutic opportunities are recently being offered by l -iminosugars. , Indeed, although typically acting as weaker and noncompetitive glycosidase inhibitors, several l -iminosugars (either alone or in combination with their d -enantiomers) have displayed noteworthy chaperoning activities toward the same enzymes in their mutated forms. , On the basis of these combined data, our research program aimed at exploring the stereoselectivity of biomolecular recognition processes ,− took us to study the role of iminosugar chirality in PCT through the analysis of the chaperoning potential of the unnatural enantiomer of 1 , i.e. N -butyl- l -deoxynojirimycin ( ent - 1 ) ( l -NBDNJ; Figure ).…”

Section: Introductionmentioning

confidence: 87%

“…18,19 Indeed, although typically acting as weaker 20 and non-competitive 18 glycosidase inhibitors, several Liminosugars (either alone or in combination with their D-enantiomers) 21 have displayed noteworthy chaperoning activities toward the same enzymes in their mutated forms. 21,22 Based on these combined data, our research program aimed at exploring the stereoselectivity of biomolecular recognition processes 18,[23][24][25][26] took us to study the role of iminosugar chirality in PCT through the analysis of the chaperoning potential of the unnatural enantiomer of 1, i.e. N-butyl-Ldeoxynojirimycin (ent-1) (L-NBDNJ; Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease

et al. 2017

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The highly stereocontrolled de novo synthesis of l-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. l-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease

et al. 2017

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“…Over the years, the increasing clinical request for oxathiolane nucleosides has justified the development of a wide variety of synthetic approaches allowing their preparation in high purity and on large scale. ,, Despite their structural simplicity, access to these compounds has represented a major synthetic challenge, because of (a) the need for a chemistry enabling stereochemical control of two potentially epimerizable stereocenters and (b) the need for stereoselective N -glycosidation methodologies required in the absence of directing groups adjacent to the glycosidation site.…”

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confidence: 99%

Highly Stereoselective Synthesis of Lamivudine (3TC) and Emtricitabine (FTC) by a Novel N-Glycosidation Procedure

et al. 2015

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The combined use of silanes (Et3SiH or PMHS) and I2 as novel N-glycosidation reagents for the synthesis of bioactive oxathiolane nucleosides 3TC and FTC is reported. Both systems (working as anhydrous HI sources) were devised to act as substrate activators and N-glycosidation promoters. Excellent results in terms of chemical efficiency and stereoselectivity of the reactions were obtained; surprisingly, the nature of the protective group at the N4 position of (fluoro)cytosine additionally influenced the stereochemical reaction outcome.

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“…The chemistry detailed in this section will concentrate on building N-nucleosides. There have been several excellent reviews on the construction of nucleosides over the past decades [ 33 – 34 65 ]. Accordingly, this section begins with an introduction on important classical approaches and older yet creative methods to provide the reader with a historical context.…”

Section: Reviewmentioning

confidence: 99%

“…Herein, we tried to explore recent developments in comparison to previously reported methods to access 1,3-oxathiolane nucleosides. Similarly, a book chapter by D’alonzo and Guaragna published in 2013 summarizes the synthesis and biological applications of these important analogues [ 34 ]. However, a brief account is presented in this section for the sake of continuity.…”

Section: Introductionmentioning

confidence: 99%

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

Aher¹,

Srivastava²,

Singh³

et al. 2021

Beilstein J. Org. Chem.

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Sugar-modified nucleosides have gained considerable attention in the scientific community, either for use as molecular probes or as therapeutic agents. When the methylene group of the ribose ring is replaced with a sulfur atom at the 3’-position, these compounds have proved to be structurally potent nucleoside analogues, and the best example is BCH-189. The majority of methods traditionally involves the chemical modification of nucleoside structures. It requires the creation of artificial sugars, which is accompanied by coupling nucleobases via N-glycosylation. However, over the last three decades, efforts were made for the synthesis of 1,3-oxathiolane nucleosides by selective N-glycosylation of carbohydrate precursors at C-1, and this approach has emerged as a strong alternative that allows simple modification. This review aims to provide a comprehensive overview on the reported methods in the literature to access 1,3-oxathiolane nucleosides. The first focus of this review is the construction of the 1,3-oxathiolane ring from different starting materials. The second focus involves the coupling of the 1,3-oxathiolane ring with different nucleobases in a way that only one isomer is produced in a stereoselective manner via N-glycosylation. An emphasis has been placed on the C–N-glycosidic bond constructed during the formation of the nucleoside analogue. The third focus is on the separation of enantiomers of 1,3-oxathiolane nucleosides via resolution methods. The chemical as well as enzymatic procedures are reviewed and segregated in this review for effective synthesis of 1,3-oxathiolane nucleoside analogues.

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Stereoselective Methods in the Synthesis of Bioactive Oxathiolane and Dioxolane Nucleosides

Cited by 6 publications

References 146 publications

N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease

N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease

Highly Stereoselective Synthesis of Lamivudine (3TC) and Emtricitabine (FTC) by a Novel N-Glycosidation Procedure

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

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