Synthesis of C -pyrimidyl nucleosides starting from alkynyl ribofuranosides

Legrave, Grégory; Youcef, Ramzi Aït; Afonso, Damien; Ferry, Angélique; Uziel, Jacques; Lubin‐Germain, Nadège

doi:10.1016/j.carres.2018.04.005

Cited by 5 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…routes explored in particular detail (Fig. 1b) [21][22][23][24] have been the reconstruction of the uracil nucleobase on a C1′-funcionalized D-ribofuranosyl moiety [25][26][27][28] or the coupling of a suitably primed heteroaryl with a glycosyl reagent, such as glycal or pentonolactone 18,20,[29][30][31][32][33] . Despite considerable efforts in method development, stereo-direction (β:α) remains an important issue 29,30,[33][34][35] .…”

mentioning

confidence: 99%

A selective and atom-economic rearrangement of uridine by cascade biocatalysis for production of pseudouridine

2023

View full text Add to dashboard Cite

As a crucial factor of their therapeutic efficacy, the currently marketed mRNA vaccines feature uniform substitution of uridine (U) by the corresponding C-nucleoside, pseudouridine (Ψ), in 1-N-methylated form. Synthetic supply of the mRNA building block (1-N-Me-Ψ−5’-triphosphate) involves expedient access to Ψ as the principal challenge. Here, we show selective and atom-economic 1N-5C rearrangement of β-d-ribosyl on uracil to obtain Ψ from unprotected U in quantitative yield. One-pot cascade transformation of U in four enzyme-catalyzed steps, via d-ribose (Rib)-1-phosphate, Rib-5-phosphate (Rib5P) and Ψ-5’-phosphate (ΨMP), gives Ψ. Coordinated function of the coupled enzymes in the overall rearrangement necessitates specific release of phosphate from the ΨMP, but not from the intermediary ribose phosphates. Discovery of Yjjg as ΨMP-specific phosphatase enables internally controlled regeneration of phosphate as catalytic reagent. With driving force provided from the net N-C rearrangement, the optimized U reaction yields a supersaturated product solution (∼250 g/L) from which the pure Ψ crystallizes (90% recovery). Scale up to 25 g isolated product at enzyme turnovers of ∼105 mol/mol demonstrates a robust process technology, promising for Ψ production. Our study identifies a multistep rearrangement reaction, realized by cascade biocatalysis, for C-nucleoside synthesis in high efficiency.

show abstract

mentioning

confidence: 99%

A selective and atom-economic rearrangement of uridine by cascade biocatalysis for production of pseudouridine

2023

View full text Add to dashboard Cite

show abstract

“…Modified nucleosides constitute a vast and diverse family of biologically active compounds (Jordheim, Durantel, Zoulim, & Dumontet, ; Mehellou & De Clercq, ; Shelton et al, ) due to their bioisosterism with the natural derivatives have always attracted the interest among synthetic medicinal chemists toward antiviral and anticancer therapeutic research (Lak et al, ; Panayides et al, ; Parker, ; Pradere et al, ). In this regard, different structural modifications have been reported (Amblard, Cho, & Schinazi, ; Blade et al, ; Borland et al, ;Flores et al, ; Legrave et al, ; Liang, Pitteloud, & Wnuk, ; Miguélez, Batchu, & Boto, ; Rao, Manmode, & Hotha, ; Romeo et al, ) in both the sugar ring as well as the nucleobase. Among the different classes of modified nucleosides, arabino configuration and its bioisosteric analogues also showed good anticancer and antiviral activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and cytotoxic evaluation of apioarabinofuranosyl pyrimidines

Sivakrishna

Islam

Santra

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

In view of the potent anticancer activity of the D-arabino-configured cytosine nucleoside (ara-C), apioarabinofuranosyl pyrimidine nucleosides were designed and synthesized from D-ribose as starting material. The synthetic strategy signifies that tosylation followed by in situ cyclization, one-pot controlled oxidative cleavage and acetylation by Pb (OAc) 4 , stereoselective nucleobase condensation, inversion of hydroxyl group and uracil group converted to cytosine as the key steps. Synthesized apioarabinofuranosyl pyrimidine nucleosides were tested using breast, colon, and ovarian cancer cell lines. However, only compound 19a, 19b, and 22b have a moderate growth-suppressive effect against the luminal A breast cancer cell line MCF7. K E Y W O R D S 2, 2 0 -anhyrouridine, apioarabinofurnosyl pyrimidines, apio nucleosides, cytotoxic activity, D-ribose, Vorbrüggen base condensation

show abstract

Highly Stereoselective C‐Glycosylation by Photocatalytic Decarboxylative Alkynylation on Anomeric Position: A Facile Access to Alkynyl C‐Glycosides

Liu

et al. 2022

Chin. J. Chem.

View full text Add to dashboard Cite

The highly stereoselective synthesis of diverse medicinally valuable alkynyl C-glycosides under mild and green reaction conditions remains a great challenge. Herein, we wish to report a visible-light induced photocatalytic decarboxylative alkynylation approach. By utilizing an iridium photocatalyst in the presence of visible light, glycosyl radicals are in-situ generated via the decarboxylation of anomeric acids and efficiently coupled with a variety of ethynylbenziodoxolones (EBXs), which allows the facile synthesis of a variety of alkynyl C-glycosides in moderate to high yields and with excellent diastereoselectivity..

show abstract

Synthesis of C -pyrimidyl nucleosides starting from alkynyl ribofuranosides

Cited by 5 publications

References 13 publications

A selective and atom-economic rearrangement of uridine by cascade biocatalysis for production of pseudouridine

A selective and atom-economic rearrangement of uridine by cascade biocatalysis for production of pseudouridine

Synthesis and cytotoxic evaluation of apioarabinofuranosyl pyrimidines

Highly Stereoselective C‐Glycosylation by Photocatalytic Decarboxylative Alkynylation on Anomeric Position: A Facile Access to Alkynyl C‐Glycosides

Contact Info

Product

Resources

About