Is it still worth renewing nucleoside anticancer drugs nowadays?

Liu, Zai-Qun

doi:10.1016/j.ejmech.2023.115987

Cited by 5 publications

(1 citation statement)

References 126 publications

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“…These analogues act by competing with natural nucleosides with improved binding to targeted enzymes or receptors with some level of selectivity. This approach has led to the discovery of clinically important antiviral and anticancer agents [1,2]. Modifications of the furanose ring have been extensively studied, and new synthetic approaches are continuously being developed.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4′-Thionucleoside Analogues Bearing a C2′ Stereogenic All-Carbon Quaternary Center

Eymard,

Manchoju,

Almazloum

et al. 2024

Molecules

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The design of novel 4′-thionucleoside analogues bearing a C2′ stereogenic all-carbon quaternary center is described. The synthesis involves a highly diastereoselective Mukaiyama aldol reaction, and a diastereoselective radical-based vinyl group transfer to generate the all-carbon stereogenic C2′ center, along with different approaches to control the selectivity of the N-glycosidic bond. Intramolecular SN2-like cyclization of a mixture of acyclic thioaminals provided analogues with a pyrimidine nucleobase. A kinetic bias favoring cyclization of the 1′,2′-anti thioaminal furnished the desired β-D-4′-thionucleoside analogue in a 7:1 ratio. DFT calculations suggest that this kinetic resolution originates from additional steric clash in the SN2-like transition state for 1′,4′-trans isomers, causing a significant decrease in their reaction rate relative to 1′,4′-cis counterparts. N-glycosylation of cyclic glycosyl donors with a purine nucleobase enabled the formation of novel 2-chloroadenine 4′-thionucleoside analogues. These proprietary molecules and other derivatives are currently being evaluated both in vitro and in vivo to establish their biological profiles.

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Section: Introductionmentioning

confidence: 99%

Synthesis of 4′-Thionucleoside Analogues Bearing a C2′ Stereogenic All-Carbon Quaternary Center

Eymard,

Manchoju,

Almazloum

et al. 2024

Molecules

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Regioselective Deacetylation in Nucleosides and Derivatives

Grabbe,

Cai

2024

ChemBioChem

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Nucleoside analogues are a promising class of natural compounds in the pharmaceutical industry, and many antiviral, antibacterial and anticancer drugs have been created through structural modification of nucleosides scaffold. Acyl protecting groups, especially the acetyl group, play an important role in the protection of hydroxy groups in nucleoside synthesis and modification; consequently, numerous methodologies have been put forth for the acetylation of free nucleosides. However, for nucleosides that contain different O‐ and N‐based functionalities, selective deprotection of the acetyl group(s) in nucleosides has been studied little, despite its practical significance in simplifying the preparation of partially or differentially substituted nucleoside intermediates. In this mini‐review, recent approaches for regioselective deacetylation in acetylated nucleosides and their analogues are summarized and evaluated. Different regioselectivities (primary ester, secondary ester, full de‐O‐acetylation, and de‐N‐acetylation) are summarized and discussed in each section.

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